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The Role of Enzyme Supplementation in Digestive Disorders

The Role of Enzyme Supplementation in Digestive Disorders

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Review ArticleAlternative Medic<strong>in</strong>e Review Volume 13, Number 4 2008Table 1. Pancreatic <strong>Enzyme</strong>s <strong>in</strong> Digestion<strong>Enzyme</strong>Enterok<strong>in</strong>ase (actually secreted<strong>in</strong> the small <strong>in</strong>test<strong>in</strong>e)Proteolytic <strong>Enzyme</strong>s:Tryps<strong>in</strong>ogen (tryps<strong>in</strong>)Chymotryps<strong>in</strong>ogen (chymotryps<strong>in</strong>)CarboxypolypeptidaseAlso various elastases andnucleasesAmylolytic <strong>Enzyme</strong>s:Pancreatic amylaseLipolytic <strong>Enzyme</strong>s:LipasePhosphalipase A1, A2EsteraseOptimal pH Range5.2-6.07.9-9.76.7-7.28.0ActionTransforms tryps<strong>in</strong>ogen <strong>in</strong>to tryps<strong>in</strong><strong>in</strong> duodenumTryps<strong>in</strong> and chymotryps<strong>in</strong> break downprote<strong>in</strong>s <strong>in</strong>to polypeptides anddipeptides; carboxypolypeptidasesplits peptides <strong>in</strong>to <strong>in</strong>dividual am<strong>in</strong>oacidsHydrolyzes starches, glycogen, andother carbohydrates (other thancellulose) <strong>in</strong>to disaccharides andsome trisaccharidesLipase hydrolyzes fats <strong>in</strong>to fattyacids and monoglycerides; phospholipasessplit fatty acids from phospholipids;esterase hydrolyzescholesterol estersThis dysfunction can occur for a variety <strong>of</strong> reasons, <strong>in</strong>clud<strong>in</strong>ggenetic predisposition, illness, <strong>in</strong>jury/trauma,excessive exercise, ag<strong>in</strong>g, toxic exposure, or a comb<strong>in</strong>ationthere<strong>of</strong>. A deficiency <strong>of</strong> pancreatic enzymes couldpotentially contribute to the development <strong>of</strong> numerousillnesses and degenerative conditions.Pancreatic <strong>Enzyme</strong> <strong>Supplementation</strong>Chymotryps<strong>in</strong>, tryps<strong>in</strong>, pancreat<strong>in</strong>, and pancrelipase,either <strong>in</strong>dividually or <strong>in</strong> comb<strong>in</strong>ation, are thekey components <strong>of</strong> most common pancreatic supplementsused <strong>in</strong> health care and are primarily extractedfrom porc<strong>in</strong>e or bov<strong>in</strong>e sources. 2 Lipase may also besynthesized from microbial sources, such as Aspergillusoryzae and Rhizopus arrhizus. 3-5U.S. Pharmacopoeia (U.S.P.) grade chymotryps<strong>in</strong>and tryps<strong>in</strong> are crystallized from ox pancreas gland extract,pancrelipase is derived from hog pancreas, and pancreat<strong>in</strong>is extracted from both hog and ox sources. 2<strong>The</strong> activity and concentration <strong>of</strong> these enzymesare determ<strong>in</strong>ed by multiple factors, <strong>in</strong>clud<strong>in</strong>g theanimal’s species, age and sex, as well as husbandry practices.<strong>The</strong> physiology <strong>of</strong> hogs, especially the pancreas,is more similar to humans than any other animal species.6 Enzymatic activity levels from pork sources areapproximately 30- to 50-percent higher than beefsources. While porc<strong>in</strong>e pancreas is particularly rich <strong>in</strong>amylase and lipase, bov<strong>in</strong>e pancreas is rich <strong>in</strong> proteolyticenzymes but substantially lower <strong>in</strong> amylase and lipase.Sow glands are high <strong>in</strong> lipase, whereas butcher hogs(young male hogs up to 90 kg <strong>in</strong> weight and six months<strong>of</strong> age) are high <strong>in</strong> protease. <strong>Enzyme</strong> levels <strong>in</strong> beef cowsand bulls differ significantly from those found <strong>in</strong> steersor heifers.Plant-Based <strong>Enzyme</strong> PreparationsAs the name implies, plant-based enzymepreparations are derived from plant sources, such asp<strong>in</strong>eapple and papaya. Bromela<strong>in</strong> is a general name forthe family <strong>of</strong> sulfhydryl-conta<strong>in</strong><strong>in</strong>g, proteolytic enzymesfrom the p<strong>in</strong>eapple fruit and stem. Bromela<strong>in</strong> also conta<strong>in</strong>sa peroxidase, acid phosphatase, several proteasePage 308Copyright © 2008 Thorne Research, Inc. All Rights Reserved. No Repr<strong>in</strong>t Without Written Permission.


Review ArticleAlternative Medic<strong>in</strong>e Review Volume 13, Number 4 2008or pH-protected to ensure activity <strong>in</strong> the small <strong>in</strong>test<strong>in</strong>e.Pancreatic lipase is a relatively fragile enzyme and becomesirreversibly <strong>in</strong>activated at a lumen pH


Review ArticleAlternative Medic<strong>in</strong>e Review Volume 13, Number 4 2008Lactose as a Supplement DiluentLactose is used as a diluent <strong>in</strong> numerouspharmaceutical and nutritional preparations, <strong>in</strong>clud<strong>in</strong>g<strong>in</strong> bromela<strong>in</strong>, papa<strong>in</strong>, peps<strong>in</strong>, and pancreat<strong>in</strong>. <strong>The</strong> U.S.Pharmacopoeia states that each milligram <strong>of</strong> NationalFormulary (N.F.) or U.S.P. peps<strong>in</strong> should digest between3,000 and 3,500 times its weight <strong>of</strong> coagulated eggalbum<strong>in</strong>. When a peps<strong>in</strong> with higher digestive activityis used it is mixed with lactose to reduce its digestivepotency to the <strong>of</strong>ficial standard.* Lactose is also theprimary substance used to dilute U.S.P. pancreat<strong>in</strong>.Each milligram <strong>of</strong> U.S.P. pancreat<strong>in</strong> is standardized toconta<strong>in</strong> no less than 25 U.S.P. units <strong>of</strong> amylase activity,2.0 U.S.P. units <strong>of</strong> lipase activity, and 25 U.S.P. units <strong>of</strong>protease. Both peps<strong>in</strong> and pancreat<strong>in</strong> preparations <strong>of</strong>higher digestive power are labeled as a whole numbermultiple (e.g., 2X, 3X).* Manufacturer analysis <strong>of</strong> rawpancreat<strong>in</strong> <strong>in</strong>dicates the pure product displays notless than 9X <strong>of</strong> the U.S.P. value. Thus, one gram <strong>of</strong> purepancreat<strong>in</strong> conta<strong>in</strong>s approximately 235,000-275,000units <strong>of</strong> amylase activity, 220,000-270,000 units <strong>of</strong>protease activity, and 18,000-40,000 units <strong>of</strong> lipaseactivity.*<strong>The</strong> United States Pharmacopeia (22nd revision),<strong>The</strong> National Formulary (17th ed), United StatesPharmacopeial Convention, Inc.: Rockville, MD;1990.<strong>The</strong> 27 lactose-<strong>in</strong>tolerant children were then given the enzymepreparations with whole milk. Both K. lactis- andA. oryzae-derived enzymes significantly reduced hydrogenbreath excretion (p


Review ArticleAlternative Medic<strong>in</strong>e Review Volume 13, Number 4 200814. Billigmann P. <strong>Enzyme</strong> therapy – an alternative <strong>in</strong>treatment <strong>of</strong> herpes zoster. A controlled study <strong>of</strong> 192patients. Fortschr Med 1995;113:43-48. [Article <strong>in</strong>German]15. Bergkvist R, Svaerd PO. Studies on the thrombolyticactivity <strong>of</strong> a protease from Aspergillus oryzae. Acta PhysiolScand 1964;60:363-371.16. Verhaeghe R, Verstraete M, Schetz J, et al. Cl<strong>in</strong>ical trial<strong>of</strong> br<strong>in</strong>ase and anticoagulants as a method <strong>of</strong> treatmentfor advanced limb ischemia. Eur J Cl<strong>in</strong> Pharmacol1979;16:165-170.17. Kiessl<strong>in</strong>g H, Svensson R. Influence <strong>of</strong> an enzyme fromAspergillus oryzae, protease I, on some components <strong>of</strong> thefibr<strong>in</strong>olytic system. Acta Chem Scand 1970;24:569-579.18. Larsson LJ, Frisch EP, Torneke K, et al. Properties <strong>of</strong> thecomplex between alpha 2-macroglobul<strong>in</strong> and br<strong>in</strong>ase,a prote<strong>in</strong>ase from Aspergillus oryzae with thrombolyticeffect. Thromb Res 1988;49:55-68.19. Vanhove P, Donati MB, Claeys H, et al. Action <strong>of</strong>br<strong>in</strong>ase on human fibr<strong>in</strong>ogen and plasm<strong>in</strong>ogen. ThrombHaemost 1979;42:571-581.20. Nair RJ, Lawler L, Miller MR. Chronic pancreatitis. AmFam Physician 2007;76:1679-1688.21. Cystic Fibrosis Foundation. www.cff.org:80/aboutcf/[Accessed October 1, 2008]22. American Diabetes Association. www.diabetes.org/about-diabetes.jsp [Accessed October 1, 2008]23. Hardt PD. Prevalence and Cl<strong>in</strong>ical Relevance <strong>of</strong> Exocr<strong>in</strong>ePancreatic Insufficiency <strong>in</strong> Diabetes Mellitus. First WorldCongress on Controversies <strong>in</strong> Obesity, Diabetes andHypertension. Berl<strong>in</strong>, Germany. October 26-29, 2006.24. Layer P, Keller J. Lipase supplementation therapy:standards, alternatives, and perspectives. Pancreas2003;26:1-7.25. Keller J, Layer P. Pancreatic enzyme supplementationtherapy. Curr Treat Options Gastroenterol2003;6:369-374.26. Dodge JA, Turck D. Cystic fibrosis: nutritionalconsequences and management. Best Pract Res Cl<strong>in</strong>Gastroenterol 2006;20:531-546.27. Graham DY. <strong>Enzyme</strong> replacement therapy <strong>of</strong> exocr<strong>in</strong>epancreatic <strong>in</strong>sufficiency <strong>in</strong> man. Relations between <strong>in</strong>vitro enzyme activities and <strong>in</strong> vivo potency <strong>in</strong> commercialpancreatic extracts. N Engl J Med 1977;296:1314-1317.28. DiMagno EP, Malagelada JR, Go VL, Moertel CG. Fate<strong>of</strong> orally <strong>in</strong>gested enzymes <strong>in</strong> pancreatic <strong>in</strong>sufficiency.Comparison <strong>of</strong> two dosage schedules. N Engl J Med1977;296:1318-1322.29. Heizer WD, Cleaveland CR, Iber FL. Gastric<strong>in</strong>activation <strong>of</strong> pancreatic supplements. Bull JohnsHopk<strong>in</strong>s Hosp 1965;116:261-270.30. Go VL, Poley JR, H<strong>of</strong>mann AF, Summerskill WH.Disturbances <strong>in</strong> fat digestion <strong>in</strong>duced by acidicjejunal pH due to gastric hypersecretion <strong>in</strong> man.Gastroenterology 1970;58:638-646.31. DiMagno EP. Controversies <strong>in</strong> the treatment <strong>of</strong> exocr<strong>in</strong>epancreatic <strong>in</strong>sufficiency. Dig Dis Sci 1982;27:481-484.32. Regan PT, Malagelada JR, DiMagno EP, et al.Comparative effects <strong>of</strong> antacids, cimetid<strong>in</strong>e and entericcoat<strong>in</strong>g on the therapeutic response to oral enzymes<strong>in</strong> severe pancreatic <strong>in</strong>sufficiency. N Engl J Med1977;297:854-858.33. Leung AY. Encyclopedeia <strong>of</strong> Common Natural IngredientsUsed <strong>in</strong> Foods, Drugs, and Cosmetics. New York, NY:John Wiley & Sons; 1980:74-76.34. Knill-Jones RP, Pearce H, Batten J, Williams R.Comparative trial <strong>of</strong> Nutrizym <strong>in</strong> chronic pancreatic<strong>in</strong>sufficiency. Br Med J 1970;4:21-24.35. Balakrishnan V, Hareendran A, Nair CS. Double-bl<strong>in</strong>dcross-over trial <strong>of</strong> an enzyme preparation <strong>in</strong> pancreaticsteatorrhea. J Assoc Physicians India 1981;29:207-209.36. Nakamura T, Takeuchi T, Tando Y. Pancreaticdysfunction and treatment options. Pancreas1998;16:329-336.37. Schneider MU, Knoll-Ruzicka ML, DomschkeS, et al. Pancreatic enzyme replacement therapy:comparative effects <strong>of</strong> conventional and enteric-coatedmicrospheric pancreat<strong>in</strong> and acid-stable fungal enzymepreparations on steatorrhoea <strong>in</strong> chronic pancreatitis.Hepatogastroenterology 1985;32:97-102.38. Sahi T. Hypolactasia and lactase persistence. Historicalreview and the term<strong>in</strong>ology. Scand J Gastroenterol Suppl1994; 202:1-6.39. Cichoke AJ. <strong>Enzyme</strong>s and <strong>Enzyme</strong> <strong>The</strong>rapy: How toJump-Start Your Way to Life-Long Good Health. LosAngeles, CA: Keats Publish<strong>in</strong>g; 2000:40.40. Lomer MC, Parkes GC, Sanderson JD. Review article:lactose <strong>in</strong>tolerance <strong>in</strong> cl<strong>in</strong>ical practice – myths andrealities. Aliment Pharmacol <strong>The</strong>r 2008;27:93-103.41. Barillas C, Solomons NW. Effective reduction <strong>of</strong> lactosemaldigestion <strong>in</strong> preschool children by direct addition<strong>of</strong> beta-galactosidases to milk at mealtime. Pediatrics1987;79:766-772.42. Rosado JL, Solomons NW, Lisker R, Bourges H.<strong>Enzyme</strong> replacement therapy for primary adult lactasedeficiency. Effective reduction <strong>of</strong> lactose malabsorptionand milk <strong>in</strong>tolerance by direct addition <strong>of</strong> betagalactosidaseto milk at mealtime. Gastroenterology1984;87:1072-1082.43. Medow MS, <strong>The</strong>k KD, Newman LJ, et el.Beta-galactosidase tablets <strong>in</strong> the treatment <strong>of</strong>lactose <strong>in</strong>tolerance <strong>in</strong> pediatrics. Am J Dis Child1990;144:1261-1264.44. Messer M, Baume PE. Oral papa<strong>in</strong> <strong>in</strong> gluten <strong>in</strong>tolerance.Lancet 1976;2:1022.45. Kelly GS. Bromela<strong>in</strong>: a literature review and discussion<strong>of</strong> its therapeutic applications. Altern Med Rev1996;1:243-257.Page 314Copyright © 2008 Thorne Research, Inc. All Rights Reserved. No Repr<strong>in</strong>t Without Written Permission.

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