Functional Dyspepsia and Gastric Acid: Any Relation?

Abstract

Gastric acid and upper gastrointestinal disorders are closely connected, and antacids and acid secretion inhibitors are commonly used in the treatment of such disorders. Gastro-oesophageal ree ux disease (GERD) and peptic ulcer disease are undoubtedly acid-related disorders (although Helicobacter pylori might be more important in patients with ulcer disease), but the relation between acid and functional dyspepsia (FD) (or non-ulcer dyspepsia) has been questioned for many years (1). Previous discussions have been hampered by poor dee nition of FD and different diseases in the upper gastrointestinal tract were in part mixed in. Although the different disease entities have been better dee ned with less overlap, the role of gastric acid in patients with FD remains obscure. The uncertainty is ree ected in the treatment. There are well-documented and effective treatments (medical and surgical) for patients with peptic ulcer disease and GERD, whereas the treatment for patients with FD remains controversial. Symptomatic improvement following treatment with acid secretion inhibitors indicates a relation between acid and FD. Numerous studies have evaluated the symptomatic effect of antacids, H2-receptor antagonists and proton-pump inhibitors in patients with FD, and meta-analyses sum up the results (2, 3). Bolling-Sternevald et al. present one further study in this issue of the Scandinavian Journal of Gastroenterology (4). Most reviews and meta-analyses, like the study by Bolling-Sternevald et al., conclude that acid secretion inhibitors are effective, but the therapeutic gain above placebo is small (in the range of 10%‐20%) and the clinical signie cance of the effect is poorly documented. The clinical benee t is also mentioned in the study by Bolling-Sternevald et al. (4). The e nding that mild abdominal pain/discomfort compared to moderate/severe symptoms was indicative of a favourable outcome, and that the PGWB index (quality of life) could not detect any signie cant differences between the treatment groups, questions the clinical usefulness of the treatment in all patients. Most studies indicate that the effect is restricted to a subset of patients (5). If the effect is restricted to a subgroup with an impressive effect, the therapeutic effect might be highly valuable to this group. With the exception of an effect in patients with ree ux-like symptoms (who might have GERD and not FD), it has been dife cult to characterize the responder. Accordingly, the ‘trial and error’ method has been used to tailor the optimal therapy for the individual patient. Various pathophysiological mechanisms in the oesophagus, stomach and duodenum might bring about acid-induced FD. A characteristic pattern of acid ree ux to the oesophagus might in some patients cause dyspepsia (without ree ux symptoms), which is effectively treated with acid secretion inhibitors (6). Acid in the stomach might also provoke symptoms. Direct installation of acid in the stomach and increased acid secretion after injection of pentagastrin provoke symptoms in patients with dyspepsia, and rebound hypersecretion after withdrawal of acid secretion inhibitors induces dyspepsia in healthy volunteers (7‐9). Sensitivity and motility in the upper GI tract are often altered in patients with FD, and acid affects both gastric and duodenal sensitivity and motility. HCl increases the sensitiveness of mucosal mechanoreceptors in the gastric wall, and acid suppressants delay gastric emptying in healthy volunteers (10, 11). Patients with FD, but not healthy volunteers, report nausea after infusion of acid in the duodenum (12, 13). Motility studies after infusion of acid in the duodenal bulb in the fasting period demonstrate decreased clearance of exogenous acid from the duodenal bulb and decreased duodenal motor activity in dyspeptic patients compared to controls (12‐14). Acid secretion inhibitors alter the antropyloroduodenal motor response to acid infusion (14). This variety of pathophysiological disturbances in patients with FD explains the dife culties in predicting response to acid secretion inhibitors in the individual patient and in characterizing the responder. Inall, it is likely that acid provokes symptoms in a subset of patients with FD through various mechanisms in the upper gastrointestinal tract. Non-acid related disturbance is the cause of symptoms in other patients. Further research should aim at expanding our understanding of the pathophysiology in patients with FD and improve the methods for predicting response to treatment in the individual patient.