Skip to main content
Log in

Pancreatic enzyme replacement therapy

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. DiMagno EP, Clain JE, Layer P: Chronic pancreatitis. In The Pancreas: Biology, Pathobiology, and Diseases, edn 2. Edited by Go VLW, et al. New York: Raven Press; 1993:665–706.

    Google Scholar 

  2. Layer P, DiMagno EP: Natural histories of alcoholic and idiopathic chronic pancreatitis. Pancreas 1996, 12:318–319.

    Article  PubMed  CAS  Google Scholar 

  3. Layer P, Keller J: Pancreatic enzymes: secretion and luminal nutrient digestion in health and disease. J Clin Gastroenterol 1999, 28:3–10. Gives further insight into the physiology and pathophysiology of secretion and luminal availability of pancreatic enzymes.

    Article  PubMed  CAS  Google Scholar 

  4. DiMagno EP, Go VLW, Summerskill WHJ: Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973, 288:813–815.

    Article  PubMed  CAS  Google Scholar 

  5. Hiele M, Ghoos Y, Rutgeerts P, Vantrappen G: Starch digestion in normal subjects and patients with pancreatic diseases, using a 13CO2 breath test. Gastroenterology 1989, 96:503–509.

    PubMed  CAS  Google Scholar 

  6. Layer P, Zinsmeister AR, DiMagno EP: Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans. Gastroenterology 1986, 91:41–48.

    PubMed  CAS  Google Scholar 

  7. Guimbaud R, Moreau JA, Bouisson M, et al.: Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans. Pancreas 1997, 14:76–82.

    Article  PubMed  CAS  Google Scholar 

  8. Layer P, Holtmann G: Pancreatic enzymes in chronic pancreatitis (state-of-the-art). Int J Pancreatol 1994, 15:1–11.

    PubMed  CAS  Google Scholar 

  9. Read NW, McFarlane A, Kinsman RJ, et al.: Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology 1984, 86:274–228.

    PubMed  CAS  Google Scholar 

  10. Spiller RC, Trotman IF, Higgins BE, et al.: The ileal brakeinhibition of jejunal motility after ileal fat perfusion in man. Gut 1984, 25:365–374.

    PubMed  CAS  Google Scholar 

  11. Layer P, Peschel S, Schlesinger T, Goebell H: Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion. Am J Physiol 1990, 258:G196-G201.

    PubMed  CAS  Google Scholar 

  12. Layer P, Schlesinger T, Goebell H: Modulation of periodic interdigestive gastrointestinal motor and pancreatic function by the ileum. Pancreas 1993, 8:426–432.

    Article  PubMed  CAS  Google Scholar 

  13. Keller J, Rünzi M, Goebell H, Layer P: Duodenal and ileal nutrient deliveries regulate human intestinal motor and pancreatic responses to a meal. Am J Physiol 1997, 272:G632-G637.

    PubMed  CAS  Google Scholar 

  14. DiMagno EP, Layer P: Human exocrine pancreatic enzyme secretion. In The Pancreas: Biology, Pathobiology, and Diseases, edn 2. Edited by Go VLW, et al. New York: Raven Press; 1993:275–300.

    Google Scholar 

  15. Layer P, Chan ATH, Go VLW, DiMagno EP: Human pancreatic secretion during phase II antral motility of the interdigestive cycle. Am J Physiol 1988, 254:G249-G253.

    PubMed  CAS  Google Scholar 

  16. Borgström B, Dahlqvist A, Lundh G, Sjövall J: Studies of intestinal digestion and aborption in the human. J Clin Invest 1957, 36:1521–1536.

    PubMed  Google Scholar 

  17. Layer P, Go VLW, DiMagno EP: Fate of pancreatic enzymes during aboral small intestinal transit in humans. Am J Physiol 1986, 251:G475-G480.

    PubMed  CAS  Google Scholar 

  18. Granger M, Abadie B, Marchis-Mouren G: Limited action of trypsin on porcine pancreatic amylase: characterization of the fragments. FEBS Lett 1975, 56:189–193.

    Article  PubMed  CAS  Google Scholar 

  19. Layer P, Jansen JBMJ, Cherian L, et al.: Feedback regulation of human pancreatic secretion: effects of protease inhibition on duodenal delivery and small intestinal transit of pancreatic enzymes. Gastroenterology 1990, 98:1311–1319.

    PubMed  CAS  Google Scholar 

  20. Layer P, Baumann J, Hellmann C, et al.: Effect of luminal protease inhibition on prandial nutrient digestion during small intestinal chyme transit [abstract]. Pancreas 1990, 5:718.

    Google Scholar 

  21. Holtmann G, Kelly DG, Sternby B, DiMagno EP: Survival of human pancreatic enzymes during small bowel transit: effect of nutrients, bile acids, and enzymes. Am J Physiol 1997, G553–G658.

  22. Kelly DG, Sternby B, DiMagno EP: How to protect human pancreatic enzyme activities in frozen duodenal juice. Gastroenterology 1991, 100:189–195.

    PubMed  CAS  Google Scholar 

  23. Thiruvengadam R, DiMagno EP: Inactivation of human lipase by proteases. Am J Physiol 1988, 255:G476-G481.

    PubMed  CAS  Google Scholar 

  24. Layer P, Hellmann C, Baumann J, et al.: Modulation of physiologic fat malabsorption in humans [abstract]. Digestion 1990, 46:153.

    Google Scholar 

  25. DiMagno EP, Go VLW, Summerskill WHJ: Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973, 288:813–815.

    Article  PubMed  CAS  Google Scholar 

  26. Langkisch PG, Lembcke B, Wemken G, Creutzfeldt W: Functional reserve capacity of the exocrine pancreas. Digestion 1986, 35:175–181.

    Google Scholar 

  27. DiMagno EP, Malagelada JR, Go VLW: Relationship between alcoholism and pancreatic insufficiency. Ann N Y Acad Sci 1975, 252:200–207.

    Article  PubMed  CAS  Google Scholar 

  28. Layer P, Yamamoto H, Kalthoff L, et al.: The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis. Gastroenterology 1994, 107:1481–1487.

    PubMed  CAS  Google Scholar 

  29. Layer P, von der Ohe MR, Holst JJ, et al.: Altered postprandial motility in chronic pancreatitis: role of malabsorption. Gastroenterology 1997, 112:1624–1634. Report from an extensive experimental study demonstrating the importance of malabsorption for motility disturbances in chronic pancreatitis that possibly contribute to symptoms.

    Article  PubMed  CAS  Google Scholar 

  30. Slaff J, Jacobson D, Tillmann CR, et al.: Protease-specific suppression of pancreatic exocrine secretion. Gastroenterology 1984, 87:44–52.

    PubMed  CAS  Google Scholar 

  31. Nakamura T, Takeuchi T: Pancreatic steatorrhea, malabsorption, and nutrition biochemistry: a comparison of Japanese, European and American patients with chronic pancreatitis. Pancreas 1997, 14:323–333.

    Article  PubMed  CAS  Google Scholar 

  32. Bond JH, Bond MD: Fate of soluble carbohydrate in the colon of rats and man. J Clin Invest 1976, 57:1158–1164.

    PubMed  CAS  Google Scholar 

  33. Bond JH, Currier BE, Buchwald H, Levitt MD: Colonic conservation of malabsorbed carbohydrate. Gastroenterology 1980, 78:444–447.

    PubMed  CAS  Google Scholar 

  34. Stephen AM, Haddad AC, Phillips SF: Passage of carbohydrate into the colon. Gastroenterology 1983, 85:589–595.

    PubMed  CAS  Google Scholar 

  35. Flourie B, Florent C, Jouany JP, et al.: Colonic breakdown of 50 g wheat starch in healthy man: effect on symptoms and fecal outputs. Gastroenterology 1986, 90:111–119.

    PubMed  CAS  Google Scholar 

  36. Mackie RD, Levine AS, Levitt MD: Malabsorption of starch in pancreatic insufficiency [abstract]. Gastroenterology 1981, 80:1220.

    Google Scholar 

  37. Patel VP, Jain NK, Agarwal N, et al.: Comparisons of bentiromide test and rice flour breath hydrogen test in the detection of exocrine pancreatic insufficiency. Pancreas 1986, 1:172–175.

    Article  PubMed  CAS  Google Scholar 

  38. Kerlin P, Wong L, Harris B, Capra S: Rice flour, breath hydrogen, and malabsorption. Gastroenterology 1984, 87:578–585.

    PubMed  CAS  Google Scholar 

  39. DiMagno EP, Malagelada JR, Go VLW, Moertel CG: Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two dosage schedules. N Engl J Med 1977, 296:1318–1322.

    Article  PubMed  CAS  Google Scholar 

  40. Sternby B, Holtmann G, Kelly DG, DiMagno EP: Effect of gastric or duodenal nutrient infusion on gastric and pancreatic lipase secretion [abstract]. Gastroenterology 1992, 102:A292.

    Google Scholar 

  41. Heizer WD, Cleaveland CR, Iber FL: Gastric inactivation of pancreatic supplements. Bull Johns Hopkins Hosp 1965, 116:261–270.

    PubMed  CAS  Google Scholar 

  42. Goebell H, Klotz U, Nehlsen B, Layer P: Oroileal transit of slow release 5-ASA. Gut 1993, 34:669–675.

    PubMed  CAS  Google Scholar 

  43. Code CF, Schlegel JF: The gastrointestinal interdigestive housekeeper: motor correlates of the interdigestive myoelectric complex of the dog. In Proceedings of the Fourth International Symposium on GI Motility. Edited by Daniel EE. Vancouver, BC: Mitchell Press; 1973:631–634.

    Google Scholar 

  44. Schlegel JF, Code CF: The gastric peristalsis of the interdigestive housekeeper. In Proceedings of the Fifth International Symposium on GI Motility. Edited by Vantrappen G. Leuven: Typoff-Press; 1975:321.

    Google Scholar 

  45. Kölbel C, Layer P, Hotz J, Goebell H: Effect of an acid protected, micro-encapsulated pancreatin preparation on pancreatogenic steattorhea [in German]. Med Klin 1986, 81:85–86.

    Google Scholar 

  46. Lankisch PG, Lembcke B, Göke B, Creutzfeldt W: Therapie der pankreatogenen Steatorrhoe: Bietet der Säureschutz für Pankreasenzyme Vorteile? Verh Dtsch Ges Inn Med 1983, 89:864–867.

    Google Scholar 

  47. Meyer JH, Lake R: Mismatch of duodenal deliveries of dietary fat and pancreatin from enterically coated microspheres. Pancreas 1997, 15:226–235. Experimental study questioning whether a further decrease in microsphere size of pancreatin preparations is associated with greater clinical benefit.

    Article  PubMed  CAS  Google Scholar 

  48. Dutta SK, Rubin J, Harvey J: Comparative evaluation of the therapeutic efficacy of a pH-sensitive enteric-coated pancreatic enzyme preparation with conventional pancreatic enzyme therapy in the treatment of exocrine pancreatic insufficiency. Gastroenterology 1983, 84:476–482.

    PubMed  CAS  Google Scholar 

  49. Hendeles L, Dorf A, Stecenko A, Weinberger M: Treatment failure after substitution of generic pancrelipase capsules: correlation with in vitro lipase activity. JAMA 1990, 263:2459–2461.

    Article  PubMed  CAS  Google Scholar 

  50. FitzSimmons SC, Burkhart GA, Borowitz D, et al.: High-dose pancreatic enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med 1997, 336:1283–1289. Important study correlating the daily dosage of pancreatin supplements and development of fibrosing colonopathy in cystic fibrosis. The relative risk is increased about 200-fold in patients receiving more than 50 kU/kg/d.

    Article  PubMed  CAS  Google Scholar 

  51. MacSweeney EJ, Oades PJ, Buchdahl R, et al.: Relation of thickening of colon wall to pancreatic-enzyme treatment in cystic fibrosis. Lancet 1995, 345:752–756.

    Article  CAS  Google Scholar 

  52. Bansi DS, Price A, Russell C, Sarner M: Fibrosing colonopathy in an adult owing to overuse of pancreatic enzyme supplements. Gut 2000, 46:283–285.

    Article  PubMed  CAS  Google Scholar 

  53. Regan PT, Malagelada JR, DiMagno EP, et al.: Comparative effects of antacids, cimetidine, and enteric coating on the therapeutic response to oral enzymes in severe pancreatic insufficiency. N Eng J Med 1977, 297:854–858.

    Article  CAS  Google Scholar 

  54. Carroccio A, Pardo F, Montalto G, et al.: Use of famotidine in severe exocrine pancreatic insufficiency with persistent maldigestion on enzymatic replacement therapy. Dig Dis Sci 1992, 37:1441–1446.

    Article  PubMed  CAS  Google Scholar 

  55. Heijerman HG, Lamers CB, Bakker W: Omeprazole enhances the efficacy of pancreatin (Pancrease) in cystic fibrosis. Ann Intern Med 1991, 114:200–210.

    PubMed  CAS  Google Scholar 

  56. Casellas F, Guarner L, Vaquero E, et al.: Hydrogen breath test with glucose in exocrine pancreatic insufficiency. Pancreas 1998, 16:481–486.

    Article  PubMed  CAS  Google Scholar 

  57. Caliari S, Benini L, Sembenini C, et al.: Medium-chain triglyceride absorption in patients with pancreatic insufficiency. Scand J Gastroenterol 1996, 31:90–94.

    PubMed  CAS  Google Scholar 

  58. Krawisz BR, Miller LJ, DiMagno EP, Go VLW: In the absence of nutrients pancreatic-biliary secretions in the jejunum do not exert feedback control of human pancreatic or gastric function. J Lab Clin Med 1980, 95:13–18.

    PubMed  CAS  Google Scholar 

  59. Hotz J, Ho SB, Go VLW, DiMagno EP: Short-term inhibition of duodenal tryptic activity does not affect human pancreatic, biliary or gastric function. J Lab Clin Med 1983, 101:488–495.

    PubMed  CAS  Google Scholar 

  60. Owyang C, Louie DS, Tatus D: Feedback regulation of pancreatic enzyme secretion: suppression of cholecystokinin release by trypsin. J Clin Invest 1986, 77:2042–2047.

    Article  PubMed  CAS  Google Scholar 

  61. Owyang C, May D, Louie DS: Trypsin suppression of pancreatic enzyme secretion: differential effect on cholecystokinin release and the enteropancreatic reflex. Gastroenterology 1986, 91:637–643.

    PubMed  CAS  Google Scholar 

  62. Adler G, Reinshagen M, Koop I, et al.: Differential effects of atropine and a cholecystokinin receptor antagonist on pancreatic secretion. Gastroenterology 1989, 96:1158–1164.

    PubMed  CAS  Google Scholar 

  63. Ihse I, Lilja P, Lundquist I: Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. Digestion 1977, 15:303–308.

    Article  PubMed  CAS  Google Scholar 

  64. Mössner J, Stange JH, Ewald M, et al.: Influence of exogenous application of pancreatic extract on endogenous pancreatic enzyme secretion. Pancreas 1991, 6:637–644.

    Article  PubMed  Google Scholar 

  65. Isaksson F, Ihse I: Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis. Dig Dis Sci 1983, 28:97–102.

    Article  PubMed  CAS  Google Scholar 

  66. Halgreen H, Thorsgaard Pedersen N, Worning H: Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis. Scand J Gastroenterol 1986, 21:104–108.

    PubMed  CAS  Google Scholar 

  67. Mössner J, Secknus R, Meyer J, et al.: Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial. Digestion 1992, 53:54–66.

    PubMed  Google Scholar 

  68. Malfertheiner P, Mayer D, Büchler M, et al.: Treatment of pain in chronic pancreatitis by inhibition of pancreatic secretion with octreotide. Gut 1995, 36:450–454.

    PubMed  CAS  Google Scholar 

  69. Bruno MJ, Haverkort EB, Tijssen GP, et al.: Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 1998, 42:92–96. Clarifies the place of enzyme therapy in palliative treatment of pancreatic cancer.

    Article  PubMed  CAS  Google Scholar 

  70. Lankisch PG (Ed.). Pancreatic enzyme therapy following surgical procedures in the gastrointestinal tract. Pancreatology 2001, 1(suppl 1):1–72.

    Google Scholar 

  71. Lankisch PG: Appropriate pancreatic function tests and indication for pancreatic enzyme therapy following surgical procedures on the pancreas. Pancreatology 2001, 1(suppl 1):14–26. Includes detailed recommendations on indications and appropriate enzyme preparations for pancreatic enzyme therapy following pancreatic surgery.

    Article  CAS  Google Scholar 

  72. Gullo L, Costa PL, Ventrucci M, et al.: Exocrine pancreatic function after total gastroectomy. Scand J Gastroenterol 1979, 14:401–407.

    PubMed  CAS  Google Scholar 

  73. Friess H, Böhm J, Müller MW, et al.: Maldigestion after total gastroectomy is associated with pancreatic insufficiency. Am J Gastroenterol 1996; 91:341–347.

    PubMed  CAS  Google Scholar 

  74. Friess H, Tempia-Callera AA, Cammerer G, Büchler MW: Indication for pancreatic enzyme substitution following gastric resection. Pancreatology 2001, 1(suppl 1):41–48.

    Article  CAS  Google Scholar 

  75. Layer P, Melle U: Indication for pancreatic enzyme substitution following small intestinal resection (short bowel syndrome). Pancreatology 2001, 1(suppl 1):49–54.

    Article  CAS  Google Scholar 

  76. Layer P, vd Ohe M, Gröger G, et al.: Intraluminal proteolytic degradation of lipase and fat malabsorption in pancreatintreated pancreatic insufficiency [abstract]. Pancreas 1992, 7:745.

    Google Scholar 

  77. Zentler Munro PL, Assoufi BA, Balasubramanian K, et al.: Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis. Pancreas 1992, 7:311–319.

    Article  PubMed  CAS  Google Scholar 

  78. Schneider MU, Knoll-Ruzicka ML, Domschke S, et al.: Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterology 1985, 32:97–102.

    PubMed  CAS  Google Scholar 

  79. Griffin SM, Alderson D, Farndon JR: Acid resistant lipse as replacement therapy in chronic pancreatic exocrine insufficiency: a study in dogs. Gut 1989, 30:1012–1015.

    PubMed  CAS  Google Scholar 

  80. Moreau J, Bousson M, Saint Marc Girardin MF, et al.: Comparison of fungal lipase and pancreatic lipase in exocrine pancreatic insufficiency in man: study of their in vitro properties and intraduodenal bioavailability. Gastroenterol Clin Biol 1988, 12:787–792.

    PubMed  CAS  Google Scholar 

  81. Raimondo M, DiMagno EP: Lipolytic activity of bacterial lipase survives better than that of porcine lipase in human gastric and duodenal content. Gastroenterology 1994, 107:231–235.

    PubMed  CAS  Google Scholar 

  82. Suzuki A, Mizumoto A, Sarr MG, DiMagno EP: Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency: a new therapy of steatorrhea? Gastroenterology 1997, 112:2048–2055.

    Article  PubMed  CAS  Google Scholar 

  83. Suzuki A, Mizumoto A, Rerknimitr R, et al.: Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs. Gastroenterology 1999, 116:431–437. Report from an important experimental study showing the superiority of bacterial lipase over porcine lipase and of high-fat over low-fat diet in pancreatic insufficiency. The data provide a rationale for the development of bacterial lipase preparations and alteration of recommendations from a low- to a high-fat diet in chronic pancreatitis.

    Article  PubMed  CAS  Google Scholar 

  84. Bodmer MW, Angal S, Yarranton GT, et al.: Molecular cloning of a human gastric lipase and expression of the enzyme in yeast. Biochim Biophys Acta 1987, 909:237–244.

    PubMed  CAS  Google Scholar 

  85. Peschke GJ: Active components and galenic aspects of enzyme preparations. In Pancreatic Enzymes in Health and Disease. Edited by Lankisch PG. Berlin-Heidelberg: Springer; 1991:55–64.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peter, L., Jutta, K. & Lankisch, P.G. Pancreatic enzyme replacement therapy. Curr Gastroenterol Rep 3, 101–108 (2001). https://doi.org/10.1007/s11894-001-0005-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-001-0005-8

Keywords

Navigation