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The Disease, The Condition, The Treatment

EPI dog just diagnosed (left) and 4 months later with proper treatment (right)

updated September 5, 2023

EPI, Exocrine Pancreatic Insufficiency, is the inability of the acinar cells in the exocrine part of the pancreas to produce and secrete the necessary enzymes needed to digest food. These main enzymes are:.

  • Amylase for digestion of carbohydrates (sugars & starches in grains, fruits & vegetables),      
  • Lipases for digestion of fat.                                          
  • Trypsin and Proteases for digestion of proteins.

EPI, is sometimes referred to as Pancreatic Hypoplasia or Pancreatic Acinar Atrophy (PAA).  

Or EPI can also be the secondary condition of a chronic illness, such as chronic pancreatitis.

 EPI is when a dog’s exocrine part of the pancreas is atrophied and can no longer produce these pancreatic digestive enzymes. It is now know that all EPI dogs have a secondary condition called SID (small intestinal dysbiosis) formerly called SIBO. SID is an imbalance in the gut flora…not enough bacteria and not enough variety of bacteria. Another secondary condition in EPI dogs that often occurs is insufficient B12 which will need to be supplemented or else the dog will never fully flourish. A dog with EPI, although eating copious amounts of food, is constantly hungry becoming undernourished and can literally waste away. Without proper treatment, the EPI dog can suffer greatly and even die a painful death from malnourishment, starvation or organ failure.

 With EPI, organs, the immune system, nervous system and all other body systems may become compromised to one degree or another.   A lack of nutrients sometimes even results in temperament changes which may express themselves in fear and/or aggression.

 It is a devastating, frustrating disease that is all too often misdiagnosed. Symptoms usually do not appear until anywhere between 80% and 95% of the exocrine pancreas acinar cells are destroyed. What makes this disease even harder to diagnose is that not all dogs display any or all of the symptoms all of the time. Any breed can have EPI, not just GSDs… see EPI…not just for German Shepherds.

The EPI diagnostic test is a simple TLI blood test. Once proper treatment is implemented it is amazing how well most EPI dogs respond and go on to live a good long quality life.

Common Symptoms 

The most common symptoms are:

  • Gradual wasting away despite a voracious appetite
  • Eliminating much more frequently, sometimes every hour or two
  • Stools are greasy voluminous yellowish cow-plops, but sometimes grayish
  • Eating their own stools, or other inappropriate substances
  • Increased rumbling sounds from the abdomen
  • Increased passing amounts of flatulence
  • Some dogs do not show any typical signs
  • Some experience intermittent watery diarrhea or vomiting
  • Some dogs even display personality changes such as fearfulness or sudden aggression

 Visuals of EPI Symptoms

Sloppy cow-patty-like EPI feces

EPI dog before and after treatment

Detecting EPI

  • EPI can manifest anytime in a dog’s life – – from a young pup to an elderly dog, with the severity and symptoms of the disease varying somewhat with each dog.  Sometimes the dog has the disease but symptoms do not appear at all, until exacerbated or triggered through a stressful physical or emotional situation.
  • Always confirm EPI with a trypsin-like immunoreactivity (cTLI) blood test (8-12 hour “food” fast). As of Sept 2023 normal range is now under review and the new values that should be considered are as follows for dogs:
  • 0 to 2.5 µg/L Diagnostic for EPI
    2.6 to 7.5 µg/L Subnormal cTLI concentration, highly suggestive of EPI. Assess response to pancreatic enzyme replacement therapy to confirm diagnosis.
    7.6 to 10.0 µg/L Subnormal cTLI concentration, EPI cannot be excluded. If signs are consistent with EPI, consider assessing response to pancreatic enzyme replacement therapy to confirm diagnosis.
    10.1 to 50.0 µg/L Result is within the reference interval.
    >50.0 µg/L The clinical significance of a cTLI concentration >50.0 µg/L is uncertain. If you have also run a cPLI and this is within the reference interval pancreatitis is unlikely.
  • Whenever there is persistent gastrointestinal upsets and weight loss, it is advisable & economical to do a cTLI blood test.

The Treatment

Successfully managing EPI, (Exocrine Pancreatic Insufficiency) is all about finding the right balance of:

  • Enzymes
  • Diet
  • Prebiotics, Prebiotics & Probiotics, or Antibiotics (if needed for SID/SIBO)
  • B12 (if needed for low or low-normal B12)

Effectively Managing the Treatment


  • The most effective enzymes are the porcine-based powdered enzymes called pancreatin. Enzyme pills are less effective and plant-based enzymes are not strong enough. Effective “average” USP Units for enzyme potency in powdered pancreatin used for EPI is:

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)

  • The best dose recommendation to start with when using powdered enzymes is 1 level teaspoon of powdered enzymes per 1 cup of dry kibble, ¾ level teaspoon of powdered enzymes per 1 cup of wet (or raw) food. Not per meal! This dose may vary slightly from one dog to another. Adjust accordingly.
  • Always add 1/4+ cup of room-temp liquid (water or broth) per cup of food and let sit for 20 minutes (incubate).

To soften the food so the enzymes can be better distributed among more food particles.

To help avoid possible mouth sores from the caustic attributes of the powdered enzymes.

  • Although incubation is not necessary for all EPI dogs, many EPI dogs do much better once this extra step is taken.
  • Mix enzymes with room temperature or slightly warm ingredients. Mixing the enzymes with cold food or liquid will temporarily inactivate the enzymes. Using hot (above 130 degrees F) food or liquid will destroy the enzymes. Microwaving or cooking with the enzymes must be avoided.
  • In countries outside the USA, if powdered pancreatin is not readily available, CREON an enteric-coated capsule used for cystic fibrosis patients, may be used successfully after some trial and error. Start by giving CREON 10 (or 12) approximately five minutes prior to a meal. Do not incubate. If poor digestion still occurs, start increasing the dose by increments of five. Dosage may vary greatly from one dog to another. Some EPI dogs do well on one CREON 10 (12) with each meal, some need two CREON 10 (12), or one CREON 25. With CREON it depends on the individual dog which dose and administration technique of CREON will work most effectively.
  • Once an EPI dog is stable for a month or so, “try” reducing the amount of enzymes being used to the lowest dose possible but at a dose that will still allow the dog to properly digest food. This is determined by continued firm stools, minimal volume and elimination frequency equal to that of a normal dog.
  • As some dogs age, enzymes supplementation may need to be increased, again, this depends on the individual dog.


This is the trickiest part of managing EPI.

  • Most EPI dogs respond best to low-fiber (grain-free) diet. With most dogs, but not all, commercial (over the counter) brand name grain-free foods with less than 4% fiber work as well or better than the prescription diets… unless there is EPI + a concurrent condition such as a food allergy/sensitivity, IBD, etc. However, not all EPI dogs respond equally well to all low fiber dog foods. Finding the right food may be trial and error. Some do better on very high-protein/low carb food, others do better with foods with minimal grain. If grain is needed try rice.
    In the beginning, feed 150%
    of what the dog normally would require until the body replenishes the weight that was lost.
  • Do not restrict fat intake, unless, once again, there is a possible concurrent condition that requires fat restriction. Dogs appear to resume their health quicker when fat % is not restricted as long as they are receiving the proper type and dose of enzymes, and, if needed, B12 and antibiotics.
  • Feed smaller portions but more often when first trying to stabilize the dog. Feeding 3 to 4 small meals a day- -at least 2 hours apart to allow for digestion- -is suggested.
  • If acid reflux/regurgitation is a problem, try adding 1 teaspoon of canned pure pumpkin to meals, or slippery elm loose powder, psyllium, or if need be, try Omeprazole. Worst case scenario, use short-term steroids. However, also check to see if a declining B12 level is the culprit. Always work with your vet when administering meds.
  • For itchy skin or a dry coat, if tolerable, try adding EFS (Essential Fatty Acids) suggested at 180mg per 10lbs per day, or on alternate days give ½ to 1 teaspoon of cold pressed (virgin) coconut oil.

Because of the very nature of EPI (pre-diagnosis/treatment) undigested food/ bacteria imbalance/not enough different bacterial strains/ excessive fermentation causes SID/SIBO in all EPI dogs. Goal is to get SID under good management.

  • In some cases, if EPI is detected very early on, once proper treatment (enzymes) is administered the good gut flora sometimes “may” re-populate the gut flora (bacteria) imbalance rendering further treatment not necessary. Much success is seen with Slippery Elm powder. Slippery Elm is a plant mucilage with prebiotics properties. Slippery Elm is given with breakfast and dinner. The following are the suggested doses: 1/8 tsp for dogs under 10lbs, ¼ tsp for dogs 10lbs to 30lbs, ½ tsp for dogs 30lbs to 80lbs, 3/4 tsp for dogs 80lbs to 100lbs, and 1 tsp for dog 100/+lbs. Mix in meal, add 1 to 2 tablespoons of water, mix and serve meal as you normally would. Incubating not necessary. Note: sometimes less Slippery Elm powder works better. Do not give if the pet has an allergy to the American ElmTree.
  • However, many will still have to resort to an antibiotic regimen to get SID/SIBO under good management.
  • The best way to assess SID/SIBO is by (1) symptoms and (2) accompanying medical ailment, in this case EPI, and treat early on for best results. Folate test results such as Culturing, Counting bacterial numbers, and Duodenal juice collection all have majors flaws in their technique rendering them inaccurate indications of SID/SIBO. Recent studies have determined that it is not the number of bacteria but rather “the type of flora and/or how the host and flora interact that are more important than numbers.”  Also recently discovered by TAMU researchers is that EPI dogs not only do not have enough bacteria n their gut flora, but they also do not have enough bacterial variety.
  • If the dog displays any repeated signs of yellowish-coloring to the stools, loose stools, gelatinous stool coating, upchucking, vomiting with bile, flatulence, lack of appetite, stomach noises, low or low normal B12 then treat for possible secondary SID/SIBO. Previously we automatically treated with antibiotics, however, we now suggest to first try addressing with a “prebiotic” , many of us use Slippery Elm powder
    Sometimes using a prebiotic, or even a prebiotic with a probiotic, is enough to get the SID under good control. If not, then we suggest using a course of Tylan (Tylosin Tartrate).
    Tylosin is preferred, Metronidazole is no longer used and it is advised not to use for any chronic gastrointestinal disturbance. Sometimes Amoxycillin is used if the Tylosin doesn’t work or doesn’t work well enough alone. Tylosin appears to work best for the majority of EPI dogs with SID/SIBO.
  • The current recommended Tylosin dosage has recently been changed to “25mg/kg BID with food for 6 weeks”, it is still advised to administer twice daily [every 12 hours] with food:
    30 lbs – 1/8 tsp                      60lb – 1/4 tsp
    90 lb – 3/8 tsp                      120 lb – 1/2 tsp
    A response to the antibiotics should be seen within 7 to 10 days- -if improvement is seen during this time period, indicating that SID/SIBO is present, the antibiotics should be continued for a total 6 weeks, or at the very least a minimum of 4 weeks.
  • Although not clinically proven … what has been observed by diligent pet owners is that some are able to completely remove a SID/SIBO-prone dog from antibiotics through a methodical process of slowly reducing the antibiotic dose after the 45 day dose administration while also 1/2 way through the Tylosin/Tylan dose administration to slowly introduce an increased inclusion of a safe, stable, and “agreeable” pre+probiotics to help re-populate the individual dog’s intestinal gut flora.
  • Prebiotics are non-digestible food components (dietary fiber) that are being fermented by intestinal bacteria. Slippery Elm is a prebiotic. This can lead to more normalization of the intestinal microbiota. In a recent study the use of fructooligosaccharides (FOS) in the diet showed a lasting advantageous effect. This syndrome is also a potential target for probiotic therapy but one must be careful when administering probiotics. Too much FOS can cause the opposite effect. Per Dr. Jorg Steiner of Texas A&M University “…unrealistic expectations have been replaced with well-defined requirements for probiotics and controlled studies of their beneficial effects.  A probiotic must be efficacious. In order to be efficacious, the bacteria must reach the intestinal lumen. This requires that the bacterial species being used in the formulation are both acid- and bile-acid resistant. Also, the bacterial species of the probiotic preparation should adhere to the intestinal mucosa to prolong the time of interaction”.
  • When possible use a 3rd party laboratory… one such lab is to verify product “claims”.

B12 (Cobalamin Deficiency)
Cobalamin deficiency occurs in approximately 82% of all EPI dogs.

  • Treatment is required for low and low-normal B12 levels with either serum vitamin B12 weekly, bi-weekly, monthly), or oral B12 (daily, couple days weekly). Both applications use the same dose amount. Generic cobalamin preparations are recommended at 1mg/ml, i.e. 1000µg/ml. Do not use B12 multivitamin or B12 complex as these are not sufficient and will also sting the dog. The conservative serum dose regimen is one dose weekly for six weeks, then one dose every two weeks for six weeks, then dose monthly. Re-measure serum cobalamin concentrations one month after last administration. The newer, less conservative serum regimen is dose weekly for 6 weeks, then one dose after 30 days and re-test 30 days after the last dose. In either case, if the cobalamin test results are normal…CONTINUE dosing until levels are above mid- range, then determine how often B12 needs to be administered on-going for the life of the dog to maintain above mid-range levels.
  • Current B12 dosage for EPI dogs (revised by TAMU Sept 2022)
    Protocol: daily administration for a total of 12 weeks and re-check serum cobalamin concentration one week after finishing supplementation.
    Dose: 250 µg in cats and 250 – 2000 µg in dogs, depending on the size of the patient: Below 22lbs = 250 µg
    22lbs to 100lbs = 1000 µg
    Above 100lbs = 2000 µg
    Protocol: daily administration for a total of 12 weeks and re-check serum cobalamin concentration one week after finishing supplementation.
  • Previous B12 (serum or pill) dosage for EPI dogs:
    dogs up to 5 kg (10 lb) = 250 µg
    dogs, 5-15kg (10-30 lb) = 400 µg
    dogs, 15-30 kg (30-65 lb) = 800 µg
    dogs, 30-45 kg (65-100 lb) = 1200 µg
    dogs above 45 kg (100 lb) = 1500 µg
    Protocol: daily administration for a total of 12 weeks and re-check serum cobalamin concentration one week after finishing supplementation.


    With some dogs, especially the smaller breeds, there sometimes appears to be some difficulty maintaining B12 levels even with weekly injections. In these cases, although no controlled study has been done yet, when re-tested these dogs manage to “improve & hold” their B12 levels if supplemented (in-between weekly injections) with B12 pills that contain the intrinsic factor. The favored product nowadays is Wonder Laboratories Pet Factor B12 or Trinfac-B Intrinsic Factor. Both are the same and uses methylcobalamin B12. Or some will use Metagenics Intrinsi B12/Folate (more expensive). Supposedly Intrinsic Factor was suspected to be species specific, however, many dogs do not do well until they use oral B12 with non-species specific Intrinsic Factor included.. Another possibility with difficult cases is to try hydroxocobalamin B12 vs. cyanocobalamin B12.

Since cobalamin is a water-soluble vitamin, excess cobalamin is excreted through the kidneys. Over-supplementation has never been reported to date. However, if there is a concurrent kidney health concern, please work with your vet before administering B12.

Additional Health Conditions with EPI

  • SID (small intestinal dysbiosis) formerly referred to as SIBO (small intestinal bacterial overgrowth) is present in all dogs with EPI
  • COBALAMIN(B12) and folate depletion. Treat with appropriate (high dose) B12 capsules or injections. 


Once a dog is positively identified EPI with a cTLI test (see Sept 2023 revision on TLI values), it is recommended to remove the dog from all breeding programs.

If possible, with puppies only, treat, stabilize then re-test again with cTLI procedure to confirm it is EPI not something else.

Unfortunately, sometimes before a dog displays symptoms, a breeding has already taken place.

Sometimes, EPI sometimes does not show up in a line until 3 to 5 or even more generations later.

Please be a responsible steward for our canine companions, once positively identified, please communicate with others to keep track of disease and share information.