Heartburn: What Could Be Causing It

Why Heartburn Happens: The Physiology Behind the Burn

The burning sensation you feel starts at the gastroesophageal junction. A ring of muscle called the lower esophageal sphincter (LES) normally prevents gastric acid from moving upward into the esophagus. When that barrier fails, hydrochloric acid (pH 1.5 to 3.5) contacts squamous epithelium that lacks the protective mucus layer found in the stomach.

Transient lower esophageal sphincter relaxations (TLESRs) are the dominant mechanism in most reflux episodes. These are neurally mediated relaxations unrelated to swallowing, triggered by vagal reflexes from gastric distension 1. A 2006 review in Gastroenterology confirmed that TLESRs account for up to 70% of reflux events in GERD patients and nearly all reflux episodes in healthy subjects. The frequency and duration of these relaxations increase with obesity, large meals, and supine positioning.

Beyond TLESRs, a structurally weak LES (resting pressure below 10 mmHg), hiatal hernia, impaired esophageal acid clearance, and delayed gastric emptying all contribute. The interplay of these factors determines whether someone experiences occasional postprandial discomfort or daily erosive esophagitis. Not every episode of heartburn means GERD, and not every case of GERD produces heartburn.

GERD: The Leading Cause

GERD is the diagnosis behind most persistent heartburn. The American College of Gastroenterology (ACG) defines it as symptoms or complications resulting from reflux of gastric contents into the esophagus 2. Population-based studies estimate that 18-28% of North American adults experience weekly reflux symptoms 3.

The 2022 ACG Clinical Guideline recommends an empiric 8-week PPI trial as the initial diagnostic and therapeutic step for patients with typical symptoms (heartburn and regurgitation) and no alarm features 2. Dr. Philip Katz, lead author of the guideline, states: "A positive response to PPI therapy should not be used alone to confirm a GERD diagnosis, as the specificity of the PPI test is limited."

PPIs suppress acid by irreversibly inhibiting the hydrogen-potassium ATPase enzyme in gastric parietal cells. Standard doses (omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg) taken 30-60 minutes before the first meal of the day produce symptom relief in approximately 60-70% of patients with nonerosive reflux disease and over 80% of patients with erosive esophagitis 4. Patients who do not respond adequately after 8 weeks should be referred for endoscopy and ambulatory reflux monitoring.

Beyond GERD: Other Causes of Heartburn

A burning substernal sensation does not automatically equal acid reflux. Several conditions mimic or overlap with GERD, and distinguishing between them changes treatment.

Eosinophilic esophagitis (EoE) is an immune-mediated condition characterized by eosinophilic infiltration of the esophageal mucosa. A 2023 meta-analysis reported a pooled prevalence of 34.4 per 100,000 in Western populations, with incidence rising steadily over the past two decades 5. Patients often present with heartburn that fails to respond to PPIs, along with dysphagia and food impaction. Diagnosis requires esophageal biopsies showing 15 or more eosinophils per high-power field.

Peptic ulcer disease produces epigastric burning that patients frequently describe as heartburn. Helicobacter pylori infection and NSAID use remain the two primary causes. The global prevalence of H. pylori infection is estimated at 43.1%, though rates vary widely by region 6.

Medication-induced esophagitis can result from pills that lodge in the esophagus and cause direct mucosal injury. Common offenders include doxycycline, alendronate, potassium chloride, and iron supplements. The fix is simple: take these medications with a full glass of water and remain upright for at least 30 minutes.

Functional heartburn, defined by the Rome IV criteria, is recurrent burning without evidence of GERD, EoE, or major esophageal motility disorder. These patients have normal acid exposure on reflux monitoring and no symptom-reflux correlation. Neuromodulators (tricyclic antidepressants at low doses, SSRIs) are the primary pharmacologic option.

Cardiac Chest Pain: The Dangerous Mimic

This is the diagnosis you cannot afford to miss. Angina pectoris and acute coronary syndrome can produce substernal burning indistinguishable from heartburn, especially in women, older adults, and patients with diabetes.

A study published in the American Journal of Medicine found that among patients presenting to the emergency department with chest pain ultimately diagnosed as cardiac in origin, 10-15% had been initially treated for acid reflux 7. The overlap exists because vagal afferents from the heart and esophagus converge on the same spinal cord segments (T1-T5).

Red flags that suggest cardiac origin include pain radiating to the jaw, neck, or left arm; association with exertion; diaphoresis; shortness of breath; and new-onset symptoms in a patient with coronary risk factors (hypertension, diabetes, hyperlipidemia, smoking, family history). Any patient with these features needs an electrocardiogram and troponin measurement before a GI workup begins.

Lifestyle and Dietary Triggers

Specific behaviors increase reflux frequency and severity. Unlike the vague advice to "eat better," the evidence points to identifiable, modifiable factors.

Obesity is the strongest lifestyle risk factor. A prospective cohort study from the Nurses' Health Study (N=10,545) showed that a BMI increase of 3.5 kg/m² or more was associated with a nearly threefold increase in frequent reflux symptoms (OR 2.80; 95% CI 2.04-3.84) 8. Excess abdominal adiposity raises intragastric pressure and disrupts the gastroesophageal junction.

Late-night eating within 2-3 hours of lying down reduces esophageal acid clearance. A Japanese cohort study demonstrated that a short dinner-to-bed interval significantly increased nighttime acid exposure 9.

Specific foods and beverages do not affect LES pressure as uniformly as often stated. Chocolate, peppermint, and alcohol do reduce LES tone in physiologic studies. Coffee triggers reflux in some individuals but not in all; a systematic review found inconsistent evidence for a dose-response relationship 10. The ACG guideline recommends that patients eliminate only the specific foods that reproducibly trigger their own symptoms rather than following a blanket restriction list.

Smoking impairs LES function, reduces salivary bicarbonate secretion (which neutralizes esophageal acid), and delays gastric emptying. Cessation is recommended for reflux management alongside its other well-established health benefits.

Bed elevation is one of the few non-pharmacologic interventions with consistent data. Raising the head of the bed by 6-8 inches using a wedge (not extra pillows, which flex the waist and can worsen reflux) reduced esophageal acid exposure time in a controlled trial published in Digestive Diseases and Sciences 11.

How Heartburn Is Diagnosed

The diagnostic pathway depends on symptom severity, duration, and the presence of alarm features.

Step 1: Clinical history. A typical presentation of postprandial substernal burning and acid regurgitation without alarm features has a positive predictive value of approximately 80% for GERD 2. The history should screen for dysphagia, odynophagia, weight loss, anemia, vomiting, and family history of upper GI malignancy.

Step 2: Empiric PPI trial. For patients under 60 with typical symptoms and no alarms, the ACG recommends an 8-week course of once-daily PPI before breakfast. A strong symptomatic response supports (but does not confirm) a GERD diagnosis.

Step 3: Upper endoscopy (EGD). Indicated for PPI non-responders, patients with alarm symptoms, and those over 60 with new-onset heartburn. EGD identifies erosive esophagitis (Los Angeles classification A through D), Barrett esophagus, strictures, EoE, and malignancy. A normal-appearing esophagus does not rule out GERD; up to 70% of patients with reflux symptoms have nonerosive reflux disease (NERD) 12.

Step 4: Ambulatory reflux monitoring. For patients with a normal endoscopy and ongoing symptoms, wireless pH capsule (Bravo) or combined impedance-pH testing performed off PPI therapy is the definitive test. It measures total acid exposure time and establishes symptom-reflux correlation. The Lyon Consensus 2.0 defines pathologic acid exposure as a total acid exposure time exceeding 6% 13.

Step 5: Esophageal manometry. Not used to diagnose GERD directly, but required before antireflux surgery to rule out achalasia and severe hypomotility. High-resolution manometry has replaced conventional manometry in most referral centers.

Treatment Options Beyond PPIs

When PPIs alone are insufficient, or when patients prefer alternatives, several evidence-based treatments exist.

H2 receptor antagonists (famotidine 20-40 mg) provide faster onset of acid suppression than PPIs but less sustained effect. They are useful for breakthrough nighttime symptoms when added to morning PPI therapy. The 2022 ACG guideline supports bedtime H2RA use in patients with documented nocturnal acid breakthrough 2.

Potassium-competitive acid blockers (P-CABs) represent the newest class of acid suppressants. Vonoprazan, approved in the U.S. in 2023 as part of a combination H. pylori eradication regimen, competitively inhibits the proton pump and achieves faster, more consistent acid suppression than PPIs. Phase III data for vonoprazan in GERD (the PHALCON-EE trial) demonstrated noninferiority to lansoprazole for healing erosive esophagitis at 8 weeks 14.

Antireflux surgery (fundoplication) is appropriate for patients with objectively confirmed GERD (positive pH study) who wish to discontinue medication long-term or who have large hiatal hernias with refractory symptoms. The LOTUS trial, a 5-year randomized comparison of laparoscopic Nissen fundoplication versus esomeprazole, showed similar remission rates in both groups at 5 years (92% surgery vs. 93% medical), though crossover was common 15.

Magnetic sphincter augmentation (LINX device) is an alternative surgical approach using a ring of titanium beads with magnetic cores placed around the LES. Five-year data showed that 85% of patients achieved at least 50% reduction in PPI use 16.

Behavioral interventions including weight loss, meal timing, bed elevation, and smoking cessation should accompany every treatment plan. A weight reduction of just 2.5-5 kg has been associated with meaningful symptom improvement in overweight patients.

Complications of Untreated Chronic Heartburn

Chronic acid exposure to the esophageal mucosa is not just uncomfortable. It carries measurable pathologic consequences.

Erosive esophagitis occurs in approximately 30% of GERD patients undergoing endoscopy. Severe erosive disease (Los Angeles grade C or D) is associated with complications including stricture, bleeding, and Barrett esophagus.

Barrett esophagus develops when the normal squamous epithelium of the distal esophagus undergoes intestinal metaplasia. This affects an estimated 5-15% of patients with chronic GERD symptoms, and it is the only known precursor to esophageal adenocarcinoma 17. The annual progression rate from nondysplastic Barrett esophagus to adenocarcinoma is 0.5% per year, according to a Danish population-based cohort study (N=11,028).

Esophageal stricture results from chronic inflammation and fibrosis. Patients present with progressive solid-food dysphagia. Treatment involves endoscopic dilation, often combined with PPI therapy to reduce recurrence.

Extraesophageal syndromes linked to GERD include chronic cough, laryngitis, asthma exacerbation, and dental erosion. The 2022 ACG guideline cautions that establishing a causal link between reflux and extraesophageal symptoms requires objective reflux documentation, as PPI response rates for these presentations are substantially lower than for typical heartburn 2.

When to Seek Immediate Medical Attention

Most heartburn is manageable with lifestyle changes and over-the-counter medications. Some presentations require same-day evaluation.

Seek emergency care if you experience substernal pain with exertional onset, radiation to the jaw or left arm, associated shortness of breath, or diaphoresis. These features raise concern for acute coronary syndrome regardless of a prior heartburn history.

Schedule an urgent appointment if you notice difficulty swallowing (solids or liquids), unintentional weight loss exceeding 5% of body weight, vomiting blood or passing black tarry stools, persistent vomiting, or symptoms that began after age 60 without a prior GERD history. The ACG guideline classifies all of these as alarm features warranting prompt endoscopy 2.

For patients already on PPI therapy, a lack of symptom improvement after 8 weeks of compliant use (correct timing, correct dose) should prompt reevaluation. The goal is not indefinite empiric treatment but a confirmed diagnosis that directs targeted therapy.