IngredientsPancreatin is a mixture of several digestive enzymes produced by the exocrine cells of the pancreas, composed of amylase, lipase, and protease. Pancreatin is sometimes called "pancreatic acid," although it is neither a single chemical substance nor an acid. It is therefore not a botanical ingredient and has no single molecular formula; it is instead a complex biological extract with activities measured in enzyme units rather than by mass alone.
Pancreatin is available, for example under the trade name Creon®, in the form of granules, pellets, or capsules containing enteric-coated microspheres, and is used medically for enzyme replacement in pancreatic insufficiency, digestive insufficiency after stomach operations, liver and biliary diseases, cystic fibrosis, and chronic pancreatitis. It is generally obtained as a mixture of natural enzymes by extraction from porcine pancreas.
Porcine pancreatin juice is closest to that of humans, with high proportions of lipase and alpha-amylase in comparison with other mammals. Therefore, porcine pancreatin is made only from the pancreas of pigs and is used to treat conditions in which pancreatic secretions are deficient, such as surgical pancreatectomy, pancreatitis, and cystic fibrosis. The enzymes in these products usually come from the pancreas in pigs. Bovine-derived preparations have also been historically available, though porcine sourcing predominates in current practice.
Pancreatin, the British Pharmacopoeia standard, is an extract of pancreas and contains enzymes with proteinase, amylase, and lipase activity; most commercial formulations are similar or identical.
A similar mixture of enzymes is sold as pancrelipase, which contains more active lipase enzyme than does pancreatin. Pancrelipases and pancreatins are similar, except pancrelipase has an increased lipase component.
The formulations are generally hard capsules filled with gastro-resistant granules. Pancreatic enzyme products are available in both prescription and non-prescription forms. In the US, pancreatic enzyme products are available as a prescription or in dietary supplements.
All prescription pancreatic enzyme products are regulated by the United States Food and Drug Administration (FDA) to ensure their effectiveness, safety, and manufacturing consistency. Over-the-counter pancreatic enzyme supplements are available without a prescription. Since they are classified as dietary supplements rather than drugs, the FDA does not control their production. While manufacturers of over-the-counter supplements are required to ensure the safety of their products, there are no controls on manufacturing consistency from one batch to the next.
Brand names include Creon, Pancreaze, Pertzye, Sollpura (Liprotamase), Ultresa, and Zenpep. Longstanding pancreatic enzyme replacement products—some in use for a century or more—fell under a 2006 FDA requirement that pharmaceutical companies with porcine-derived products submit a New Drug Application (NDA) for each; Creon (AbbVie Inc.), the first of the commercial products approved after the FDA directive, reached market in 2009.
The starting material is in the main pig's pancreas, either fresh or frozen, from which originally only the water and fat had been removed. However, because of the sensitivity of the enzymes, such removal had hitherto had to be carried out very cautiously. In the processes conventionally used to this day, drying and defatting are carried out with solvents which dissolve water and fat simultaneously, for example acetone or higher alcohols.
For the application of pancreatin in pharmacological products it is preferred to substantially maintain the intrinsic high level of activity of the different digestive enzymes. However, these enzymes can be subject to degradation, for example upon storage, and are particularly sensitive to elevated temperatures. Thus, pancreatin requires carefully controlled conditions during the overall handling, manufacturing, and storage process.
The first observations and experimental demonstrations that pancreatin could be used to improve protein and fat digestion in animals and human patients are from the 19th century, soon after Claude Bernard had revealed the essential role of pancreatic secretion in digestion.
The digestive enzymes — amylase, lipase, trypsin, etc. — secreted by the pancreas into the intestine, were discovered in the mid to late 19th century. Demonstration of their effectiveness in breaking down fats, proteins, and starches to smaller molecules was gradual. Discovery of this principle of digestive enzymes as a primary function of the pancreas included, among many other contributors, Johann Nepomuk Eberle (1798–1834) of Bavaria, Claude Bernard (1813–1878) of Paris, Alexander Danilevsky of St. Petersburg (in 1862), and Willy Kühne (1837–1900) of Amsterdam and Heidelberg.
Pancreatin was used in medicine already in the 19th century, and because of its effectiveness and safety, it is on the WHO (World Health Organization) list of drugs.
Pancreatic enzymes have been used as medications since at least the 1800s. Pancreatin enzyme products of porcine or bovine origin have been available in the United States for the treatment of exocrine pancreatic insufficiency since before the enactment of the Federal Food, Drug, and Cosmetic Act of 1938. With the exception of one PEP approved in 1996, PEPs have been marketed without New Drug Applications and were considered as dietary supplements.
In the 1960s, Irving Innerfield conducted landmark research in the area of pancreatic enzymes, primarily relating to the clinical use of trypsin, chymotrypsin, and pancreatin as well as streptokinase (a microbial proteolytic enzyme).
During more than 100 years of commercialization of pharmaceutical products containing pancreatin, no case has been reported where patients have been affected by pancreatin contaminated by any virus.
The concept of using proteolytic pancreatic enzymes as a therapy beyond digestion also has a distinct historical thread. The Gonzalez protocol — a regimen using high-dose pancreatic enzyme supplements among cancer patients — is based on a theory promulgated by the Scottish anatomist John Beard in the early years of the last century. This theory holds that cancer is one disease emanating from ectopic germ cells, which are allowed to grow due to a deficiency of proteases. According to this theory, supplemental treatment with pancreatic enzymes is required to digest the cancerous cells. This theoretical framework, though not validated by subsequent clinical evidence (see §6 below), shaped a strand of alternative medical practice in Europe and North America throughout the 20th century.
Professor Heinrich Wrba, who for many years was head of the Austrian Cancer Research Institute at the University of Vienna, believed that enzyme therapy should be considered a highly effective causal anticancer compound. Dr. Wrba's interest in cancer was piqued when he lost a daughter to leukemia. He devoted his life to educating oncologists in Germany and around the world about enzyme therapy.
Pancreatin typically contains three principal types of enzymes, each responsible for targeting specific macronutrients: Protease, which catalyzes the hydrolysis of proteins into smaller peptides and ultimately into individual amino acids; Amylase, which facilitates the breakdown of complex carbohydrates such as starch into simpler sugars like maltose and glucose; and Lipase, which breaks down dietary fats (triglycerides) into free fatty acids and glycerol. Together, these enzymes work synergistically to promote the complete digestion of proteins, carbohydrates, and lipids, ensuring optimal nutrient absorption in the small intestine.
The trypsin found in pancreatin works to hydrolyze proteins into oligopeptides; amylase hydrolyzes starches into oligosaccharides and the disaccharide maltose; and lipase hydrolyzes triglycerides into fatty acids and glycerols.
The proteases (proteolytic enzymes) enable dietary proteins to be broken down into smaller, more easily absorbed particles. This effect is boosted by the presence of trypsin and chymotrypsin, two pancreatic endoproteases.
While the global content of lipase, protease, and amylase activities in porcine pancreatic extracts are well characterized, little is known about individual enzymes. Researchers have characterized the lipase, phospholipase, cholesterol esterase, and galactolipase activities of porcine pancreatic extracts and compared them with those of porcine and human pancreatic juices.
Porcine pancreatin contains a significant amount of purines. In patients receiving high doses, this can lead to increased intestinal absorption of purines — a pharmacologically relevant consideration in patients with predisposing conditions (see §8).
The pancreatic enzymes in pancreatin catalyze the hydrolysis of fats to monoglycerides, glycerol, and free fatty acids; protein into peptides and amino acids; and starch into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby mimicking digestive enzymes physiologically secreted by the pancreas.
Exocrine pancreatic insufficiency (EPI) is the consequence of several different diseases which all share a common pathophysiologic end result of inadequate enzyme digestion. Mechanisms of EPI include inadequate synthesis and secretion of pancreatic enzymes, decreased stimulation, pancreatic ductal obstruction, and decreased pancreatic enzyme activity in the small bowel.
Pancreatin reduces the absorption of iron from food in the duodenum during digestion — a secondary mechanistic effect that has clinical relevance for patients with coexisting iron-deficiency anemia.
The enzymatic activity of pancreatin is primarily exerted within the gastrointestinal lumen and is transient, corresponding to the digestive process.
Pancreatin's established primary action is in the gastrointestinal system. Pancreatic enzyme supplements (which include chymotrypsin, trypsin, amylase, lipase, pancreatin, and combinations of one or more) not only aid digestion but also assist in a surprising variety of bodily functions including detoxification, immunity, aging, blood fluidity, and tissue repair. An inadequate production of, or an excessive requirement for, pancreatic enzymes can occur for a variety of reasons including genetics, illness (including cystic fibrosis, chronic pancreatitis, and pancreatic cancer), surgery (such as after pancreatectomy or gastrointestinal bypass surgery), injury, exercise, aging, and toxins (both endogenous and exogenous).
The established, pharmacologically recognized body systems and health areas associated with pancreatin are:
Pancreatin is an effective enzyme supplement for replacing missing pancreatic enzymes and aids in the digestion of foods in cases of pancreatic insufficiency. This is the most rigorously studied and best-supported application, with a strong body of RCT-level and meta-analytic evidence.
Meta-analytic evidence: Seven RCTs, randomizing a total of 282 patients, were assessed qualitatively. PERT increased the coefficient of fat absorption (CFA) by WMD 26.56 (95% CI: 20.35–32.76, I² = 79.6%, P < 0.001) compared with baseline, and by WMD 17.97 (95% CI: 12.61–23.34, I² = 76.7%, P < 0.001) compared with placebo. Coefficient of nitrogen absorption, stool fat excretion, stool nitrogen excretion, and stool weight were all significantly improved in PERT compared with baseline and placebo, with no statistical differences in adverse events.
2024 systematic literature review: Researchers identified 26 journal publications and two conference abstracts, reporting on 22 randomized control trials, four observational studies, and two single-arm interventional studies. The most reported treatment was pancrelipase, specifically Creon® (n=12). Fourteen studies reported coefficient of fat absorption (CFA) results. Across studies, patients experienced a considerable increase in CFA post-initiation of treatment regardless of intervention or timepoint. Mean change in CFA ranged from 7.5% in patients with CP who received placebo to 36% in patients with CP treated with Creon®. This systematic literature review confirmed that PERT is an effective and tolerable treatment option for patients with EPI.
Key RCT example — Creon 40000 MMS in chronic pancreatitis: Of 62 patients randomised (34 pancreatin, 28 placebo), 61 completed treatment. Patients receiving pancreatin had a statistically significant greater improvement in fat absorption from baseline to the end of double-blind treatment compared with those receiving placebo, with a least squares mean change in CFA of 18.5% (95% CI: 15.8–21.2) versus 4.1% (95% CI: 1.0–7.2), resulting in a treatment difference of 14.4% (95% CI: 10.3–18.5; P = 0.001). Patients receiving pancreatin also had a statistically significant greater improvement in nitrogen absorption and greater reductions in mean stool fat, stool frequency, and stool weight compared with those receiving placebo.
Evidence strength: Strong — multiple RCTs and a quantitative meta-analysis consistently demonstrate benefit in fat and nitrogen absorption; this is a well-established, FDA-approved therapeutic use.
Pancreatic enzyme replacement therapy (PERT) is the current standard of care for exocrine pancreatic insufficiency in people with cystic fibrosis. The treatment helps the body digest and absorb nutrients from foods and liquids.
While pancreatic enzyme replacement therapy does not completely normalize pancreatic insufficiency, it does result in an increase in fat absorption above 85% in most patients with CF, and the advent of this therapy has contributed to a significant improvement in the outcomes of these patients. Additionally, PERT allows patients with CF to eat a normal diet high in fat, absorb necessary nutrients, avoid many of the disabling GI symptoms associated with pancreatic insufficiency, and grow and develop more appropriately.
A Cochrane review noted that there are no high-quality trials comparing PERT to placebo in individuals with CF. However, when comparing enteric-coated microspheres (ECM) to enteric-coated tablets (ECT), ECM has superior outcomes regarding abdominal pain, stool frequency, and fecal fat excretion, suggesting ECM's significant efficacy among patients with CF. There are no outcome differences among the various formulations of ECMs.
As respiratory complications are the main cause of morbidity and mortality in CF patients, maintaining an adequate nutritional status improves the overall prognosis and survival.
Evidence strength: Strong clinically, though no direct head-to-head placebo RCT of PERT in CF. Indirect evidence, clinical guidelines, and decades of observational data support its status as standard of care.
A recent meta-analysis on PERT's efficacy in patients with chronic pancreatitis showed that PERT significantly improved CFA and CNA, and among randomized controlled trials PERT improved GI symptoms and decreased fecal weight, fecal fat, and nitrogen excretion.
The 2016 multicenter real-world evidence study also found that pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with chronic pancreatitis or type 2 diabetes, with greater treatment compliance associated with improved gastrointestinal symptom profiles.
Evidence strength: Strong — supported by multiple RCTs and meta-analyses.
Pancreatin has been used to treat pancreatic exocrine insufficiency which is often associated with cystic fibrosis, chronic pancreatitis, post-pancreatectomy, post-gastrointestinal bypass surgery (e.g., Billroth II gastroenterostomy), and ductal obstruction from neoplasm (e.g., of the pancreas or common bile duct).
An FDA-registered study of VIOKACE (pancrelipase) assessed safety in a single, multicenter, randomized, parallel, placebo-controlled, double-blind study of 50 patients, ages 24–70 years, with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy.
Evidence strength: Moderate to strong — supported by RCTs, with FDA approval extended to post-surgical EPI; clinically considered standard of care.
A prospective multicenter trial examined pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase-1 concentrations. The study was listed on PubMed (PMID: 17103488) as a clinical trial. Research has consistently shown that a subset of patients with both type 1 and type 2 diabetes have concurrent EPI, and PERT may provide benefit in that population.
Evidence strength: Preliminary to moderate — the intersection of diabetes and EPI is an emerging area; dedicated RCTs are limited.
Research has explored whether some patients diagnosed with diarrhea-predominant IBS may have unrecognized EPI. Patients presenting to tertiary hospital outpatient clinics with IBS-D completed validated questionnaires and gave stool samples where fecal elastase-1 concentration was measured. Patients with fecal elastase-1 <100 µg/g represented EPI and those between 100–200 µg/g underwent testing for pancreatic pathology. Of 140 patients studied (mean age 60 years, 75.7% female), EPI was found in 5% (95% CI: 2.2–10.4%).
A 2024 study in Scientific Reports examined the addition of a pancreatin derivative to standard IBS treatment: The patients were divided into two groups: one receiving standard dual treatment (otilinium bromide + simethicone) and the other receiving a triple therapy including a pancreatin derivative in addition to the standard treatment. Clinical scores including VAS, Bristol Stool Chart, IBS-SSS, and IBS-QOL were assessed before and after treatment. The study comprised 121 patients, with 58 (47.9%) receiving dual therapy and 63 (52.1%) receiving triple therapy. The findings suggest that adding pancreatin to standard therapies significantly enhanced the quality of life for patients with both IBS and type 2 diabetes, demonstrating improvements across various symptom measurements.
Evidence strength: Preliminary — only applicable to the subset of IBS patients with underlying EPI, and the broader IBS-pancreatin relationship is not well established in large-scale RCTs.
The effect of oral pancreatic enzyme supplementation (Creon 10,000 in a dose of 1,000 units of lipase per gram of ingested dietary fat) on fat malabsorption was evaluated in an open study in 24 patients with HIV infection. Pancreatic enzyme supplementation was highly effective in reducing fecal fat loss.
Evidence strength: Weak to preliminary — based on a single open study with a small sample; more rigorous trials in this population are lacking.
A specific historical and clinical claim — that high-dose oral pancreatic enzymes could treat cancer systemically — was formally tested in an NIH-funded study. The US National Cancer Institute, through its office of Complementary and Alternative Medicine, funded phase III clinical trials of a controversial treatment for advanced pancreatic cancer. The treatment protocol, the Gonzalez regimen, involves a programme of dietary modification, nutritional supplements, and "detoxification" through coffee enemas. Patients with stage II–IV pancreatic cancer were enrolled.
A nonrandomized, controlled clinical trial compared the effectiveness of standard treatment with that of the Gonzalez regimen in patients whose pancreatic cancer could not be removed by surgery. Patients treated with standard chemotherapy survived an average of 14 months and patients treated with the Gonzalez regimen survived only an average of 4.3 months. In addition, patients treated with chemotherapy reported a better quality of life than those treated with the Gonzalez regimen. The US Food and Drug Administration has not approved the Gonzalez regimen or any of its components as a cancer treatment.
Evidence strength: Does not support use — the one controlled clinical trial comparing enzyme therapy to chemotherapy for pancreatic cancer showed inferior outcomes for the enzyme regimen, and the FDA has not approved any component of this regimen as a cancer therapy.
PERT may be given orally or via a feeding tube. Different brands are available, including Creon (marketed by AbbVie), Pertzye (by Digestive Care Inc.), Pancreaze (marketed by Vivus), Relizorb (by Alcresta Therapeutics), as well as Zenpep and Viokace (both marketed by Nestlé Health Science).
Dosage is universally expressed in lipase units (IU or USP units), not by total protein mass. Many basic and clinical studies use either international units (IU) or United States Pharmacopeia (USP) units. Commercial products in the United States are rated in USP units (1 IU = 3 USP units).
Adult doses reported in clinical guidelines and research:
Pediatric doses (cystic fibrosis-specific):
Maximum dose thresholds:
Post-pancreatectomy clinical trial dosing:
Several authors recommend a PERT dose for snacks that corresponds to half the dose established for main meals. Other authors suggest that the optimum control of symptoms is achieved by patients who auto-adjust PERT according to fat intake rather than following a fixed dose.
Pancreatic enzymes are on the World Health Organization's List of Essential Medicines. In 2023, it was the 258th most commonly prescribed medication in the United States, with more than 1 million prescriptions.
Pancreatin, the British Pharmacopoeia standard, is an extract of pancreas and contains enzymes with proteinase, amylase, and lipase activity. The preparation is also included in the European Pharmacopoeia and the United States Pharmacopeia (USP), where enzyme activity — particularly lipase activity — is the primary specification parameter. Batch-to-batch consistency with respect to chemical identity, biological activity of different classes of enzymes including specific activity, and identity and purity levels should be demonstrated. Since pancreatin is referenced in a New Drug Application, the agency expects the pancreatin Drug Master File to meet current ICH Q6B requirements for specifications. Specifications for the drug substance should include tests for identity, biological activity of different classes of enzyme, purity, and other relevant attributes.
People use prescription pancreatic enzyme products to treat digestion problems that occur when the pancreas has been removed or is not working well. Prescription products are FDA-approved for pancreatic insufficiency.
A primary warning concerns the potential for fibrosing colonopathy. This is a rare but severe condition characterized by the narrowing and scarring of the colon wall, predominantly observed in young patients with cystic fibrosis who are prescribed high doses of high-strength pancreatic enzymes. Fibrosing colonopathy is primarily observed in pediatric patients with cystic fibrosis receiving very high doses of pancreatin. It involves the development of strictures in the colon and necessitates immediate medical attention and discontinuation of the enzyme preparation.
A rare, serious adverse reaction has been described in association with high-dose use of pancreatic enzyme replacement in the treatment of cystic fibrosis patients. Caution should be exercised when doses of PERT exceed 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day).
The high purine content of pancreatic extracts can precipitate hyperuricosuria (excess uric acid in urine) and hyperuricemia (excess uric acid in blood), which poses a risk for patients with a history of gout or renal lithiasis (kidney stones).
Elevated serum uric acid levels can potentially contribute to joint pain or metabolic imbalance. A rare but reported side effect, especially with high-dose therapy, is uric acid nephrolithiasis (kidney stones). In predisposed individuals, increased uric acid levels may precipitate acute gouty arthritis. This concern is particularly relevant in patients with gout, renal impairment, or those on high-protein diets.
Although exceedingly rare, severe hypersensitivity reactions, including anaphylaxis, can occur, particularly in individuals with a history of allergy to porcine proteins. Because pancreatin is a porcine-derived product, there is a theoretical but extremely low risk of transmitting viral diseases from pigs to humans, although rigorous testing and manufacturing processes mitigate this.
Care should be taken to ensure that pancreatin preparations are not chewed or retained in the mouth to avoid irritation of oral mucosa. Perianal irritation — severe redness and excoriation around the anus, particularly in children — is caused by the passage of active proteolytic enzymes in the stool.
The most common adverse events (≥6% of patients treated with pancrelipase) are abdominal pain, flatulence, headache, cough, decreased weight, early satiety, and contusion. In a placebo-controlled RCT, treatment-emergent adverse events occurred in 12 patients on pancreatin and in seven on placebo; none led to study discontinuation.
Pancreatin generally has a low potential for significant drug interactions. However, certain considerations are pertinent: concurrent administration of antacids containing calcium or magnesium may theoretically reduce the efficacy of enteric-coated pancreatin preparations by altering gastric pH and potentially causing premature dissolution of the enteric coating.
Pancreatin reduces the absorption of iron from food in the duodenum during digestion; this interaction has significance for patients on iron supplementation or those with iron-deficiency states, as enzyme supplementation with meals may impair simultaneous iron uptake.
Caution should be exercised when prescribing pancreatin to patients with gout, renal impairment, or hyperuricemia.
There is a theoretical risk of viral transmission with all pancreatic enzyme products. Caution should be exercised when administering pancreatin to a patient with a known allergy to proteins of porcine origin.
Because of the complexity of pancreatin extract products, it is unlikely that currently available physiological and biological analytical tools would be able to demonstrate that the active ingredients in pancreatic extract products from two different batches or manufacturers are the same. Current United States Pharmacopeia (USP) monograph tests are insufficient to characterize the API to meet ICH guidelines. This issue is especially pertinent for over-the-counter dietary supplement pancreatin, which is not regulated by the FDA as a drug, and while manufacturers are required to ensure the safety of their products, there are no controls on manufacturing consistency from one batch to the next.
Health conditions that Pancreatin may help support.
Pancreatin is a multi-enzyme extract from animal (porcine or bovine) pancreas containing amylase, lipase, and protease. It is a clinical standard for supporting digestion and is used in pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency. Clinical evidence for its digestive efficacy is robust.
Body systems that Pancreatin may help support.
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