EPI * Exocrine Pancreatic Insufficiency

managing EPI

Enzymes  (Digestions section below enzyme):  Enzyme section Updated: April 23, 2010

The convenient method of treatment for EPI is with porcine replacement enzymes (not enzyme supplements). These enzymes are needed to break down all foods that a dog ingests. Although raw  pancreas is considered an excellent treatment, this is not always obtainable, hence the preference for pancreatic replacement enzymes.

If you live outside the USA, please check with your vet if any of the porcine-based enzyme products listed below are available in your country.

Enzyme potency in the USA is measured in USP units
(this is a different measurement than elsewhere in the world).
The necessary 3 ingredients (enzymes) with any EPI enzyme product are porcine-based
Lipase, Protease & Amylase.
If you live outside the USA and are trying to determine the proper amount of enzymes to use, please share these USA USP Units with your vet or pharmacist and have them work with you on determining the proper amount.

In the USA, the potency of the "powdered" porcine-based replacement enzyme range from:

33,600 to 71,400 USP of Lipase (needed to digest fats and oils)
280,000 to 495,000 USP of Protease (needed to digest proteins)
280,000 to 495,000 USP of Amylase needed to digest carbohydrates)
 
Most often, the initial recommended dose is 2.8 grams or 1 teaspoon of enzymes with each meal (approximately 1 cup of food) . But talk to your vet- -they need to determine what the proper dose is for your individual dog. Beware... many "over-the-counter enzyme supplement" products do not supply enough of the proper amount of enzymes needed for an EPI dog. When determining what product to use, talk to your vet and/or other EPI dog owners.

If you would like to try using raw pancreas;  fresh beef, pork or lamb pancreas are recommended. Raw BEEF Pancreas is available for purchase in the USA at http://www.hare-today.com/  One to three or four ounces of raw pancreas can replace one teaspoon of pancreatic extract. Raw pancreas may be frozen in cubes for future use and thawed naturally, but never heat on the stove or in the microwave.

Powdered enzymes may be kept in tightly sealed double plastic bags and then in a sealed contained in the refrigerator to lengthen the longevity of the stored enzyme, however, it is very important to be kept dry since moisture ruins the enzymes.

Enzyme tablets do not appear to work as well other products such as the powders or even enteric coated capsules.

Once an EPI dog is stable, the goal is to reduce the amount of enzymes given to the smallest dose possible without causing a flare-up.

BIOCASE V made by Thomas Labs, 800-359-8387. Available from Amazon

CREON (available in  Australia, Canada, Europe, South America, the UK & the U.S) these are enteric coated granules in capsules, do not break open and incubate on food as instructed for all other enzymes....although in some cases these capsules may be opened and sprinkled on top of the food- - if and only if- - served immediately, as long as the dog does not chew the granules.   CREON is commonly used in many places outside the U.S.  The CREON enzyme capsule products comes in 5, 10, 20 strengths.  The one that seems most suited to treating EPI dogs is CREON 10 which has 10,000 USP of Lipase, 37,500 USP of Protease, 33,200 USP of Amylase.

The CREON the potency measurement comparison is as follows:

CREON 10 Composition : 150 mg Pancreatin
Amylase 8,000 PhEur units (BP Units) also equals 33,400 USP units
Lipase 10,000 PhEur units (BP Units) also equals 10,000 USP units
Protease 600 Ph Eur units (BP units) also equal 37,500 USP units

CREON 25 Composition : 300 mg Pancreatin
Amylase 18,000 PhEur units (BP Units) also equals 74,700 USP units
Lipase 25,000 PhEur units (BP Units) also equals 25,000 USP units
Protease 1,000 Ph Eur units (BP units) also equal 62,500 USP units

If you are interested in purchasing CREON on-line..... one of our EPI FORUM members, Frank, put together a fabulous database on CREON including the brand name, website address, the cost of the CREON, shipping costs, and breakdown of price per capsule. This PDF is a wealth of information. Although these prices are as of April 2010 and may fluctuate with the exchange rate and/or price change.. it will give you a snapshot of price and availability. Please feel free to check it out. Click on: CREON pricing-3a.pdf

EPIZYME8  made by V.E.T. Pharmaceuticals, 800-766-7543 www.allivet.com

EUROBIOL (available in France)  http://drugs-about.com/drugs-e/eurobiol.html

GENERIC PANCREATIN (available in the US but can be shipped to certain countries outside of the US) Many people on the EPI FORUM use these generic enzymes for a savings of anywhere between 30-50%. If you are interested in ordering bulk-priced supplemental pork-based enzymes manufactured in the US, they can be directly purchased from http://www.enzymediane.com/

  • Pancreatin 6x10  (batch from 3/25/10)
    Lipase 70,840 USP units, Protease 448,000 USP units, Amylase 512,000 USP Unit.  COST:  8 oz for $42, 1 kilo for $134  (shipping included)
  • Pancreatin 8x10
  • Lipase 111,720 USP units, Protease 579,600 USP units, Amylase 694,400 USP Unit.  COST:  8 oz for $52, 1 kilo for $154  (shipping included)
    For Your Information:   1 kilo = 35.274 ounces
HARE TODAY - Raw Ground Beef Pancreas   http://www.hare-today.com/
  • Ground Beef pancreas (can be used as an alternative to pork enzymes) $2.29 per pound. Click on Raw Pet Foods and then select "Organ meats" 
LYPEX (available in England and Europe)  is an enzymatic concentrate derived from the porcine pancreas gland, available in capsules, must be opened and sprinkled on food. Do not incubate on the food. The purified and concentrated pancreatic enzymes are made into micro-pellets and each pallet is enteric-coated. This gives 100% protection to the enzymes from the damaging degradative acids present in the stomach.

Within ten minutes of the pellets passing the stomach to the alkaline environment of the small intestine the protective enteric coating dissolves and releases the protected enzymes to maximize digestion.

PANAKARE PLUS  Enzymatic concentrate derived from the porcine pancreas gland with serum concentrations of fat soluble vitamins A, E &D.  made by Neogen Corp, 800-477-8201   http://www.drugs.com/vet/panakare-plus-powder.html

PANCREASE-V  a porcine pancreatic replacement enzyme for EPI dogs mfg in Canada
http://www.bionicheanimalhealth.com/Products.aspx?ProductID=43&PatientTypeID=12
however... this product may be  purchased for $60 per 114 gram bottle through http://www.crossborder-pet-services.com/

PANCREZYME is an enzymatic concentrate derived from the porcine pancreas gland, available in powder form. made by Virbac Animal Health, 800-338-3659

PANCREX (available in the UK)  enteric coated capsules http://www.vetuk.co.uk/index.php?main_page=product_info&products_id=37

PANCREPLUS  http://www.drugs.com/vet/pancreplus-powder.html

TRYPLASE (Available in the UK )   http://www.vetuk.co.uk/index.php?main_page=product_info&products_id=164

VIOKASE an enzymatic concentrate derived from the porcine pancreas gland, available in powder or tablet form.  Made by Axcan Pharma, 800-950-8085

(plant enzymes may be attempted to use for EPI dogs with severe allergies to porcine enzymes) TOTAL-ENZYMES In some cases, a dog may have pork-based allergies, or meat protein allergies. If so, you may want to try an alternative plant-based enzyme. But please realize... plant enzymes are "supplements", EPI dogs need "replacement enzymes" however, if you have to use plant enzymes because your EPI dog medically cannot tolerate pork enzymes, there have been some EPI cases (not all) that have had success using this product. At the very least, you will need to double the recommended dose. We always advise against plant enzymes, but sometimes there are situations where porcine-based enzymes are not an option.  If you click on this PetEnzymes icon it will take you directly to their site:
pet enzymes
 For those who do not have access to porcine powdered enzymes but do have access to CREON and are interested in learning more about it (enteric coated capsules)....you might be interested in the following USA FDA regulations just approved CREON for human consumption on May 2009 for the use in the USA for in Exocrine Pancreatic Insufficiency http://www.fda.gov/

FDA NEWS RELEASE

FOR IMMEDIATE RELEASE
May 7, 2009

Media Inquiries:
Rita Chappelle, 301-796-4672
Consumer Inquiries:
888-INFO-FDA


FDA Approves Pancreatic Enzyme Replacement Product for Marketing in United States
Creon designed to help those with cystic fibrosis, others with exocrine pancreatic insufficiency

The U.S. Food and Drug Administration announced today that it has approved Creon (pancrelipase), a pancreatic enzyme replacement product designed to help patients with cystic fibrosis and others with exocrine pancreatic insufficiency (EPI) digest and absorb nutrients from foods. Creon is the first FDA-approved delayed-release pancreatic enzyme replacement product to be marketed in the United States as a result of the agency's unapproved drugs initiative.

Creon, which contains a mixture of digestive enzymes extracted from the pancreas of pigs, helps patients lacking the enzymes needed to digest fats, proteins and sugars from food. Creon is approved for use in pediatric and adult patients.

The FDA had required the manufacturer of Creon to submit, and the agency has approved, a Risk Evaluation and Mitigation Strategy (REMS), which includes a Medication Guide, to advise patients on risks associated with high doses of Creon, and the theroretical risk of transmission of viral disease from pigs to patients. A rare bowel disorder, called fibrosing colonopathy, can result from a patient's high-dose use of Creon. While this condition is serious and may require surgery, a patients' chances of having this condition may be reduced through their adherence to dosing instructions in the labeling. 

The risks of a rare bowel disorder and viral transmission described in the Medication Guide are considered to be risks related to all porcine (pig)-derived pancreatic enzyme products, including Creon.

Instructions for dosing based on weight and age should be followed carefully. Creon may be sprinkled on food. Because Creon is a delayed-release drug, patients should never crush or chew the capsule as this would cause an early release of the enzymes and a reduction in enzyme activity.

“The approval of Creon will allow patients to have access to an approved pancreatic enzyme replacement product that meets FDA standards for effectiveness, safety, and manufacturing consistency,” said Donna Griebel, M.D., director, Division of Gastroenterology Products within FDA's Center for Drug Evaluation and Research (CDER).

The FDA's Office of Compliance and Office of New Drugs within CDER worked with Creon's manufacturer, Solvay Pharmaceuticals, through the agency's unapproved drugs initiative to help the company come into compliance with federal laws by obtaining FDA approval. The agency continues to encourage the manufacturers of all other unapproved pancreatic enzyme products (PEPs) to work with the agency to obtain market approval. All PEPs must obtain FDA approval by April 28, 2010, or be removed from the marketplace.

“Like other medically necessary drugs, the FDA is exercising its enforcement discretion while it works with the manufacturer toward gaining approval of these drugs,” said Deborah Autor, director, Office of Compliance, CDER. “FDA approval is critical, and the manufacturers of these products have a responsibility to the American public to ensure that patients have drugs that meet our standards of safety, effectiveness, quality, and labeling.”

People who are allergic to pork and pork products, suffer from gout or kidney disease, have difficulty swallowing, are pregnant or who plan to become pregnant, or are breastfeeding, should discuss the use of Creon with their health care professional.  Common side effects of Creon include flatulence (gassiness), abdominal pain, headache, and dizziness.

Creon and other pancreatic enzyme products are made from pancreatic organs of pigs used for food. There is a theoretical risk of contracting a viral infection from pig-derived medicines, but no human illness has been reported.

Health care professionals and consumers may report serious adverse events (side effects) or product quality problems with the use of this product to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.

  • Online
  • Regular Mail: use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
  • Fax: 800-FDA-0178
  • Phone: 800-FDA-1088

For more information on Creon, visit FDA's Web site.

 
 

NUTRITION & DIGESTION

FROM:  Encyclopedia of Canine Clinical Nutrition, Pibot P., Biourge V. and Elliott D.A. (Eds.). International Veterinary Information Service, Ithaca NY - Last updated: 8-Jan-2008; (www.ivis.org), A4203.0108

The Most Common Digestive Diseases: The Role of Nutrition

A.J. German1 and J. Zentek2  - 1Faculty of Veterinary Sciences, University of Liverpool, United Kingdom. 2Faculty of Veterinary Medicine, University of Berlin, Germany.

Gastrointestinal problems are a major concern for small-animal practitioners. Specifically chronic disorders of the digestive tract can be difficult to manage because of the limitations of the diagnostic procedures and the multiplicity of possible causes. The current chapter summarizes the basic facts on gastrointestinal physiology of dogs including the intestinal microflora and the immune system. The most frequent digestive disorders are presented in a problem orientated manner including diagnostic aspects and medical and dietary treatment. The role of dietetics is considered specifically for each of the different types of disease considered.    

1. Digestive Tract Physiology

The small intestine (SI) is the principal site for digestion and absorption of nutrients, and is key to electrolyte and fluid absorption. The villi and microvilli contribute to the huge surface area, which facilitates absorption and assimilation of nutrients. Enterocytes are highly specialized cells involved in absorption processes. A brush border (or microvillus membrane; MVM) is present on the luminal surface of the enterocytes, and contains enzymes necessary for digestion of nutrients. Carrier proteins assist in the transport of amino acids, monosaccharides and electrolytes. The turnover of both enterocytes and microvillar proteins is influenced by luminal factors such as pancreatic enzymes, bile salts and bacteria.

Digestion and Absorption of Food

Proteins

Protein digestion is initiated in the stomach by the enzyme pepsin. It is inactivated once it has passed into the duodenum. Protein digestion in the small intestine is carried out by pancreatic and MVM enzymes. Peptides and free amino acids are produced by the digestive processes and small peptides and amino acids are absorbed by specific carriers in the MVM Digestion and absorption of proteins. 

Lipids

Dietary fats are emulsified by their interaction with bile acids in the small intestine, and subsequently digested by the pancreatic enzymes lipase, phospholipase and cholesterol esterase. Triglycerides are digested to monoglycerides and free fatty acids. In combination with bile acids, micelles are formed enabling absorption as monoglycerides and free fatty acids .Bile acids are reabsorbed by a specific carrier mechanism in the ileum, and then recycled by the liver. After absorption, long-chain fatty acids are re-esterified to triglycerides, incorporated into chylomicrons and then enter the lymphatics. Medium and short chain fatty acids were originally thought to be absorbed directly into the portal circulation, but recent work has questioned this theory (Sigalet et al., 1997). Digestion and absorption of fats. 

Carbohydrates

Starch is the major digestible polysaccharide in common food and is degraded by pancreatic amylase to maltose. Maltose and other dietary disaccharides (lactose and sucrose) are digested by MVM enzymes to constituent monosaccharides, which are then absorbed by specific transporters or by facilitated transport. Monosaccharides are then transported across the basolateral membrane into the portal circulation Digestion and absorption of carbohydrates. 

Minerals

Macrominerals and trace elements are mainly absorbed from the small intestine, but the large intestine may also take part in the absorption processes. Active calcium absorption is subjected to regulatory mechanisms that are mediated by vitamin D, parathyroid hormone and calcitonin. These homeostatic mechanisms allow the organism to adapt to the different dietary intakes within certain limits. However, in dogs a fraction of dietary calcium is absorbed by passive processes. Phosphorus is less well studied and seems to be regulated by similar mechanisms. Magnesium is absorbed without homeostatic regulation so that the blood magnesium levels have a higher variation. Sodium, potassium and chloride are mainly absorbed in the small intestine and the absorption rates normally exceed 90 per cent. The trace elements are mainly absorbed from the small intestine, but the colon may also contribute to the absorption of trace elements. The absorption rates of zinc, iron and manganese are subjected to regulatory mechanisms. Active transport systems have been demonstrated for manganese and copper. Other elements are absorbed by passive diffusion.

Vitamins

Lipid-soluble vitamins (A, D, E and K) are dissolved in mixed micelles, and passively absorbed across the MVM.

Water-soluble vitamins, most notably B vitamins, are absorbed by passive diffusion, facilitated transport or active transport. The absorptive mechanisms for folic acid and vitamin B12 are more complicated, summarized here: Assimilation of folate. Dietary folate is present in the diet as a conjugated form (with glutamate residues). This conjugate is digested by folate deconjugase, an enzyme on the microvillar membrane, which removes all but one residue, before uptake via specific carriers situated in the mid-small intestine.Assimilation of folate. Dietary folate is present in the diet as a conjugated form (with glutamate residues). This conjugate is digested by folate deconjugase, an enzyme on the microvillar membrane, which removes all but one residue, before uptake via specific carriers situated in the mid-small intestine.

Assimilation of cobalamin. Following ingestion, cobalamin is released from dietary protein in the stomach. It then binds to non-specific binding proteins (e.g. "R-proteins"). In the small intestine cobalamin transfers onto intrinsic factor (IF), which is synthesized by the pancreas. Cobalamin-IF complexes pass along the intestine until the distal small intestine, where cobalamin is transported across the mucosa and into the portal circulation.Assimilation of cobalamin. Following ingestion, cobalamin is released from dietary protein in the stomach. It then binds to non-specific binding proteins (e.g. "R-proteins"). In the small intestine cobalamin transfers onto intrinsic factor (IF), which is synthesized by the pancreas. Cobalamin-IF complexes pass along the intestine until the distal small intestine, where cobalamin is transported across the mucosa and into the portal circulation.

Intestinal Microflora

The resident bacterial flora is an integral part of the healthy intestinal tract and influences development of microanatomy, aids in digestive processes, stimulates the development of the enteric immune system, and can protect against pathogen invasion. Healthy individuals are immunologically tolerant of this stable flora, and loss of tolerance may contribute to the pathogenesis of chronic enteropathies e.g., inflammatory bowel disease (IBD).

The populations of bacterial flora quantitatively increase from the duodenum to colon, and are regulated endogenously and by a number of factors, including intestinal motility, substrate availability, various bacteriostatic and bacteriocidic secretions (e.g., gastric acid, bile and pancreatic secretions). A functional ileocolic valve is the anatomical barrier between the colonic and small intestinal microflora. Abnormalities or dysfunction in any of these factors may lead to bacterial flora abnormalities, which may be quantitative or qualitative.

The normal SI flora is a diverse mixture of aerobic, anaerobic and facultative anaerobic bacteria. The total upper small intestinal bacterial counts reported in humans is less than 103-5 CFU*/mL. (* CFU: Colony Forming Unit)

There is currently no consensus as to what constitutes a "normal" SI population in healthy dogs; some studies suggest that healthy dogs can harbor up to 109 CFU/mL aerobic and anaerobic bacteria in the proximal SI. Therefore, the "cut-off" for normal flora in dogs cannot be extrapolated from humans, and descriptions of small intestinal bacterial overgrowth (SIBO) in dogs using a cut-off value of 105 may be spurious. The intestinal microflora is subjected to endogenous and exogenous regulatory influences. Diet composition will impact the concentrations of bacteria in the gut. High protein diets favor the growth of proteolytic bacteria, especially clostridia, while certain fermentable fibers stimulate the saccharolytic bacteria, for instance bifidobacteria and lactobacilli.

Role of the Mucosal Immune System

The SI mucosa has a general barrier function, but must also generate a protective immune response against pathogens, whilst remaining "tolerant" of harmless environmental antigens such as commensal bacteria and food. Yet despite recent advances in our understanding of the structure of and interactions in the immune system, it is still unclear as to how it decides to respond to or become tolerant of a particular antigen.

The gastrointestinal tract harbors the largest number of immune cells in the body. The gut-associated lymphoid tissue (GALT) consists of inductive and effector sites. Inductive sites comprise Peyer's patches, isolated lymphoid follicles, and the mesenteric lymph nodes, whilst effector sites comprise the intestinal lamina propria and epithelium.

Such a distinction, however, is not absolute, and there is overlap between the functions of these different sites. The population of immune cells is diverse and includes T and B lymphocytes, plasma cells, dendritic cells, macrophages, eosinophils and mast cells. Protective immune responses are critical for guarding against pathogen invasion, and both cell-mediated (synthesis of cytotoxic cells) and humoral (immunoglobulin production) responses can be produced. However, of equal if not greater importance is maintenance of mucosal tolerance. This is not surprising, given that the majority of luminal antigens are derived from innocent dietary components or endogenous microflora. Generation of active immune responses to such ubiquitous molecules is both wasteful and potentially harmful, since it could lead to uncontrolled inflammation. Indeed, a break down in immunological tolerance to commensal bacteria is thought to be a critical step in the pathogenesis of inflammatory bowel disease.

Whilst the mechanisms by which mucosal tolerance actually occurs have been well characterized, the fundamental question of how the GALT decides when to and when not to become tolerant remains unresolved. Nevertheless, the critical cell in generating tolerance is the CD4+ T-cell, either by down-regulatory cytokine synthesis (e.g., TGF-β, or IL-10) or via cell-cell interactions (e.g., through CD25+, the IL-2 receptor). Interestingly, the cytokines that mediate tolerance (namely TGF-β, and IL-10) also facilitate IgA production, the most important mucosal immunoglobulin. Therefore, generation of mucosal tolerance could potentially occur in parallel to specific IgA responses. Interestingly, IgA "coats" the mucosal surface and protects by immune exclusion (i.e. preventing antigens from crossing the mucosal barrier). Given that immune exclusion limits the amount of antigen to which the mucosal immune system is exposed, its effect is also "tolerance-generating" because it minimizes immune responsiveness.

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