Of all the organs in the human body, the pancreas has the greatest capability for synthesizing proteins. Much of this protein-building ability is dedicated to synthesis of intestinal enzymes. These enzymes include lipase, which digests fat; amylase, which digests carbohydrates; and protease, which digests proteins.
Pancreatic enzyme insufficiency is most commonly caused by chronic pancreatitis, cystic fibrosis, or pancreatic resection for pancreatic cancer. When the pancreas loses > 90% of its ability to produce digestive enzymes, fat and protein digestion is impaired, which can cause steatorrhea (excess fecal fat), azotorrhea (excess fecal nitrogen), vitamin malabsorption, and weight loss.
Indigestion, also known as “dyspepsia,” is classified as either organic dyspepsia (ie. produced by identifiable causes, such as Helicobacter pylori or nonsteroidal anti-inflammatory use) or functional dyspepsia.[3] Functional dyspepsia is a diagnosis of exclusion; the cause is unknown in most patients. Although functional dyspepsia does not appear to reduce life expectancy, symptoms result in considerable morbidity and medical expense and affect an estimated 20%-25% of people in the western world.
Current guidelines recommend acid suppression with H2-antagonists (eg, ranitidine) or proton pump inhibitors (PPIs) (eg, omeprazole) for functional dyspepsia. Prokinetic drugs (eg, metoclopramide) and tricyclic antidepressants are also sometimes used, but research is limited and inconclusive. Pancreatic enzyme supplements are sometimes used empirically, but evidence is limited. In a small study of 18 healthy volunteers, the combination of lipase 30,000 US Pharmacopeia (USP) units, protease 112,500 USP units, and amylase 99,600 USP units reduced bloating, gas, and fullness after a high-fat meal.
Some researchers have suggested that functional dyspepsia might be caused by mild functional pancreatic disorder.Pancreaticenzyme therapy has not been studied in patients with functional dyspepsia.
More than a dozen pancreatic enzyme drug products were available before 2005. These products contained either bovine-derived pancreatin or porcine-derived pancrelipase, containing lipase, amylase, and protease. The US Food and Drug Administration (FDA) required all pancreatic enzyme products to obtain a new drug application and submit proof of efficacy, safety, bioavailability, and product quality by 2010. Currently, 7 pancreatic enzyme products have received FDA approval: Creon®, Pancreaze®, Pertzye™, Ultresa™, Viokace™, Zenpep®, and Pancrelipase™ 5000.
All of these products are porcine-derived pancrelipase (which is a generic as well as a brand-name product). No products containing bovine-derived pancreatin, which is much less active than pancrelipase, have FDA approval. All products except Viokace™ are enteric-coated for bioavailability in the small intestine; Viokace™ must be coadministered with a PPI.
Pancreatic enzymes are also available as dietary supplements. Some products are labeled “pancreatin,” with lipase, amylase, and protease listed as constituents; other products contain individual enzymes. “Digestive enzyme” products (eg, Digest Gold™) typically list lipase, amylase, and protease as ingredients, along with other enzymes, such as lactase and alpha-galactosidase. The FDA does not require bioavailability testing of dietary supplements, so the stability of these products in the stomach and efficacy in the small intestine are unknown.
Patients older than 55 years who present with new-onset dyspepsia should be evaluated to rule out underlying cancer, although gastric cancer is rare in the United States. Patients with alarm features — including unexplained weight loss; anorexia; early satiety; vomiting; progressive dysphagia (difficulty swallowing); odynophagia (painful swallowing); bleeding; anemia; jaundice; an abdominal mass; lymphadenopathy; a family history of upper gastrointestinal tract cancer; or a history of peptic ulcer, previous gastric surgery, or cancer — should also receive further investigation for a serious underlying disorder.
Patients with documented functional dyspepsia (ie, organic dyspepsia ruled out) may be managed symptomatically. Lifestyle interventions, such as avoiding high-fat meals and foods that precipitate the patient’s symptoms and eating frequent and smaller meals throughout the day, may be helpful. Acid-suppressing medications may be useful in some patients.
In summary, the usefulness of pancreatic enzymes has not been studied in patients with functional dyspepsia. Adverse effects of pancrelipase have been similar to those with placebo; the most common adverse effects are gastrointestinal.
In patients with refractory functional dyspepsia who have not responded to other guideline-supported measures, a trial of an FDA-approved pancreatic enzyme product for a couple of weeks might be considered, given the generally benign adverse effect profile of enzyme treatment. However, until more research is available, off-label use of pancreatic enzymes for functional dyspepsia cannot be routinely recommended.
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