Pepsin
Also known as: Pepsin, Gastric protease, EC 3.4.23.1 (Pepsin A)
Overview
Pepsin is a proteolytic enzyme produced in the stomach that breaks down dietary proteins into smaller peptides and amino acids. It is secreted as an inactive precursor, pepsinogen, which is activated by the acidic environment of the stomach, with optimal activity at pH 2-3. Pepsin supplements are used to aid digestion, particularly in cases of hypochlorhydria or impaired protein digestion. Research on pepsin is well-established in physiology and gastroenterology, with studies exploring its role in extraesophageal reflux and diagnostic applications. The evidence base includes experimental studies, clinical trials, and systematic reviews. Pepsin's activity is pH-dependent, becoming inactive in neutral or alkaline conditions. It is often combined with hydrochloric acid in digestive enzyme supplements to mimic gastric conditions.
Benefits
Pepsin facilitates protein digestion by hydrolyzing peptide bonds, improving protein breakdown and absorption, which can be beneficial in digestive insufficiency or hypochlorhydria. Pepsin-derived peptides may possess antimicrobial properties, contributing to gastric defense against pathogens. Salivary pepsin measurement is useful in diagnosing laryngopharyngeal reflux, with meta-analyses showing moderate diagnostic accuracy. Pepsin acts rapidly in the stomach postprandially, and diagnostic pepsin detection reflects recent reflux episodes. Meta-analysis data show moderate diagnostic accuracy for salivary pepsin in reflux-related conditions.
How it works
Pepsin is activated from pepsinogen in the acidic gastric pH, with optimal activity at pH 2-3. It cleaves peptide bonds, preferentially at aromatic amino acids, breaking proteins into smaller peptides. Pepsin activity declines sharply above pH 5, becoming inactive in neutral or alkaline conditions. Pepsin and its peptides may contribute to antimicrobial defense by disrupting bacterial viability and biofilm formation. In reflux pathology, pepsin can damage esophageal tissue at intermediate acidic pH (1.6-2.0) but is inactive at very low or neutral pH.
Side effects
Pepsin is generally recognized as safe when used as a digestive aid, with no significant adverse effects reported in clinical studies or reviews. However, pepsin itself can contribute to mucosal damage in reflux disease when refluxed into the esophagus or extraesophageal tissues, especially at mildly acidic pH. No major drug interactions or contraindications are documented. Caution is advised in patients with active esophageal or gastric mucosal injury. Pepsin requires an acidic environment to function, and conditions that reduce stomach acid may impair its effectiveness.
Dosage
Clinical dosing guidelines for pepsin supplements are not well standardized. Pepsin is often combined with hydrochloric acid (as betaine HCl) in digestive enzyme supplements to mimic gastric conditions. Effective doses depend on the formulation; there is no consensus on the minimum effective dose from RCTs. It is best taken with meals to aid protein digestion. Absorption is not relevant as pepsin acts locally in the stomach. Dosing should be determined based on individual needs and product specifications.
FAQs
Is pepsin supplementation effective for indigestion?
Pepsin aids protein digestion and may help in hypochlorhydria, but high-quality RCTs on supplementation efficacy are limited. Consult a healthcare professional for personalized advice.
Can pepsin cause harm?
Pepsin itself can damage esophageal tissue if refluxed, but oral supplementation in normal gastric conditions is safe. Individuals with reflux should exercise caution.
How is pepsin measured diagnostically?
Salivary pepsin assays detect reflux episodes in laryngopharyngeal reflux with moderate sensitivity and specificity. This helps in diagnosing and managing reflux-related conditions.
Does pepsin work without stomach acid?
Pepsin requires acidic pH for activation and function; without acid, pepsin is inactive. Adequate stomach acid is essential for pepsin to effectively digest proteins.
Research Sources
- https://www.ncbi.nlm.nih.gov/books/NBK537005/ – This source provides a general overview of pepsin's role in protein digestion within the stomach. It highlights pepsin's activation from pepsinogen in an acidic environment and its function in breaking down proteins into smaller peptides and amino acids.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3216344/ – This systematic review and meta-analysis on pepsin in reflux analyzed RCTs on reflux interventions and highlighted pepsin’s damaging role at intermediate acidic pH in esophageal tissue. It challenged the traditional view that pepsin is inactive at low acidity, showing pepsin can still cause damage under certain conditions.
- https://aoe.amegroups.org/article/view/6128/html – This experimental study demonstrated that peptides generated from pepsinogen have significant antimicrobial activity against gastric pathogens, reducing bacterial viability and biofilm formation in vitro and in mouse models. This highlights a secondary protective role of pepsin beyond digestion.
- https://www.elsevier.es/en-revista-brazilian-journal-otorhinolaryngology-english-edition--497-articulo-diagnostic-utility-salivary-pepsin-in-S1808869422001847 – This meta-analysis included 17 studies with ≥30 participants, showing pooled sensitivity ~62-68% and specificity ~57-74% for salivary pepsin in diagnosing laryngopharyngeal reflux. The analysis demonstrated no publication bias and moderate diagnostic accuracy, supporting clinical utility.
- https://www.ijbcp.com/index.php/ijbcp/article/view/1483 – This study investigates the effects of pepsin on gastric health. It provides insights into pepsin's role in maintaining the balance of the gastric environment and its potential impact on digestive disorders.
