Becoming an “exPERT” on Pancreatic Enzyme Replacement Therapy

As part of its exocrine functions, the pancreas produces several important digestive enzymes, including amylase, protease, and lipase, which are secreted into the small intestine shortly after ingesting a meal. These enzymes begin the process of digestion of the macronutrients from a meal – carbohydrates, proteins, and lipids, respectively. If pancreatic exocrine function is altered or insufficient, pancreatic enzyme replacement therapy (PERT) can be a crucial tool in avoiding malabsorption and ultimately reducing the risk of malnutrition.  

What is PERT?

PERT involves patients taking prescribed pancreatic enzymes when eating a meal. (There are also options for patients who are enterally fed.) PERT medications generally include amylase, protease, and lipase. While amylase and protease can be compensated in other portions of the gastrointestinal system, lipase secretion is minimal through extra-pancreatic mechanisms. As a result, most pancreatic enzyme formulations will have a larger proportion of lipase, with amylase and protease present in smaller amounts. 

Who needs PERT?

In general, patients require PERT when they have exocrine pancreatic insufficiency (EPI). This means a patient’s pancreas is not able to effectively manufacture and release pancreatic enzymes. These patients typically present with symptoms or suspicion of malabsorption. Common conditions that require PERT include:  

Pancreatic disorders: 

• Acute or chronic pancreatitis 
• Pancreatic surgery or resection 
• Unresectable pancreatic cancer 
• Benign pancreatic tumor
• Shwachman–Diamond Syndrome
• Cystic fibrosis  

Extra-pancreatic disorders: 

• Type 1 or Type 2 diabetes  
• Celiac disease
• Gastrointestinal surgery
  • Bariatric surgery
  • Total pancreatectomy
• HIV
• Sjogren’s Syndrome
• Aging 

The signs and symptoms of EPI include:

• Steatorrhea (characterized by large-volume, foul-smelling stools) 
• Diarrhea (often shortly after consuming a meal)
• Stool that is oily, greasy, discolored (pale, yellow, tan, or clay‐colored), abnormally foul–smelling, difficult to flush, and/or of loose consistency 
• Excessive flatulence, bloating 
• Abdominal cramping or pain 
• Fecal urgency 
• Weight loss despite adequate oral intake 
• May have low serum levels of fat-soluble vitamins (A, D, E, and K)

How is EPI diagnosed?

The gold standard for diagnosing EPI is a 72-hour fecal fat quantification. However, the use of this test is often limited due to the high fat consumption required (>100 grams of fat daily for three days) and is often not realistic for the patient. Fecal elastase is a simpler and reliable alternative that is less invasive and time-consuming to conduct for EPI evaluation.  

The fecal elastase level is not affected by enzyme replacement therapy. If the stool sample is too diluted by watery diarrhea, it may be inaccurate and require a new sample. A qualitative fecal fat collection requires intake of 60 g of fat in one day, and all stool to be collected. Serum pancreatic enzymes are not considered a reliable tool to diagnose pancreatic insufficiency.   

Depending on which test is ordered, below are guidelines on interpreting results: 

• 72-hour fecal fat quantification: 
  • Less than 7 g of fat per 24 hours is considered “normal”  
  • Output of > 7 g of fat is indicative of malabsorption 
  • Output of > 15 g of fat is indicative of severe malabsorption 
• Fecal elastase
  • A “low” level indicates EPI  
  • Depending on the lab cut points, moderate pancreatic insufficiency is defined at 100 to 200 μg/mL, and severe pancreatic insufficiency as < 100 μg/mL  
• Qualitative fecal fat collection 
  • Positive or negative result 
  • The severity of fat malabsorption is not indicated 

How is PERT dosed?

Pancreatic enzymes are dosed in units of lipase, but also contain protease and amylase in small amounts, depending on the manufacturer. Adults generally require 500 to 4,000 USP units of lipase per gram of fat ingested or 500 to 2,500 USP units of lipase/kg/meal and 250 to 1,250 lipase units/kg/snack. The maximum dose of pancreatic enzymes is 2,500 USP units of lipase/kg/meal.  

This has been recommended due to the risk of fibrosing colonopathy associated with very high doses of PERT in pediatric patients with cystic fibrosis. While this has not been seen as commonly in other patient populations, the maximum dosing may affect the amount of enzyme insurance companies will provide.   

Other PERTinent tips: 

• Appropriate administration of PERT is vital to the effectiveness of the medication. Patients should be instructed to take their pancreatic enzymes with meals. If the patient is taking multiple capsules of pancreatic enzymes at mealtimes, separating the capsules throughout the meal can be helpful to maximize effectiveness.   
• Provide education to the patient on meal sizes and how they relate to their prescribed dosing. This can help preserve the number of capsules of enzymes they have per month. While it is not necessarily harmful to take more enzymes at one time, it may not be necessary and can be wasteful and pricey, as PERT can be an expensive medication.   
• Monitor stool frequency and consistency in relation to meals when adjusting dosing. Monitoring bowel habits when introducing or adjusting a PERT regimen is most helpful in finding a dosing regimen that works best.   
• Currently, all FDA-approved PERT medications are porcine-derived. Be cognizant of patients with a pork allergy or those who may avoid pork products for religious or cultural reasons.  

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References:  

Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. How does the pancreas work? [Updated 2021 May 25]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279306/  

Tian C, Ghodeif AO, Azer SA, Gillespie E. Pancreatic Insufficiency. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. [Updated 2025 September 14] Available from: https://www.ncbi.nlm.nih.gov/books/NBK555926/  

Perbtani Y, Forsmark CE. Update on the diagnosis and management of exocrine pancreatic insufficiency. F1000Res. 2019;8:F1000 Faculty Rev-1991. Published 2019 Nov 26. doi:10.12688/f1000research.20779.1  

Capurso G, Traini M, Piciucchi M, Signoretti M, Arcidiacono PG. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol. 2019 Mar 21;12:129-139. doi: 10.2147/CEG.S168266. PMID: 30962702; PMCID: PMC6432881.  

Chaudhary A, Domínguez-Muñoz JE, Layer P, Lerch MM. Pancreatic Exocrine Insufficiency as a Complication of Gastrointestinal Surgery and the Impact of Pancreatic Enzyme Replacement Therapy. Dig Dis. 2020;38(1):53-68. doi:10.1159/000501675  

MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [Updated 2024 August 12]. Fecal Fat. Available from: https://medlineplus.gov/ency/article/003588.htm   

Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO. Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1220-1228.e4. doi: 10.1016/j.cgh.2018.01.027. Epub 2018 Jan 31. PMID: 29374614; PMCID: PMC6402774.  

Schwarzenberg, Sarah Jane. “Pancreatic Enzymes Clinical Care Guidelines.” Cystic Fibrosis Foundation, 1 Jul. 2021, www.cff.org/medical-professionals/pancreatic-enzymes-clinical-care-guidelines#pancreatic-enzymes-clinical-care-guidelines-executive-summary.  Accessed 16 October 2025. 

Berry, A. J., & Bilbo, A. (2024). Exocrine pancreatic insufficiency and pancreatic exocrine replacement therapy in clinical practice. Nutrition in clinical practice: official publication of the American Society for Parenteral and Enteral Nutrition, 39 Suppl 1, S78–S88. https://doi.org/10.1002/ncp.11124  

Murray, G., Ramsey, M. L., Hart, P. A., & Roberts, K. M. (2024). Fat malabsorption in pancreatic cancer: Pathophysiology and management. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 39 Suppl 1, S46–S56. https://doi.org/10.1002/ncp.11129