Vitamin B12 Supplementation for Chronic Enteropathies or Exocrine Pancreatic Insufficiency in Dogs and Cats

Vitamin B12 Supplementation for dogs or cats with EPI or chronic enteropathy

Dogs and cats with exocrine pancreatic insufficiency (EPI) and/or chronic enteropathies (CE) frequently suffer from secondary vitamin B12 (cobalamin) deficiencies.

Let’s have a refresher of these diseases and vitamin B12, and then discuss recent findings.

Signs of EPI or CE

EPI is not a CE.

A hallmark sign of EPI is voluminous yellowish or grayish soft “cow patty” stools that is accompanied by a voracious appetite, diarrhea and extreme thinness. Dogs and cats diagnosed with EPI must take digestive enzymes for life.

CE is characterized by chronic vomiting and diarrhea, along with additional signs such as loss of appetite, weight loss and other clinical symptoms.

Purpose of Vitamin B12

Vitamin B12 helps with cognitive and nerve function, red blood cell production, the digestive tract, and energy.

Signs of Vitamin B12 Deficiency

Signs of cobalamin deficiency include: lack of energy, weakness, loss of appetite, diarrhea, weight loss, loss of muscle mass and confusion.

Mechanisms Causing the Vitamin B12 Deficiency

If you are not a fan of biology, please feel free to skip this section.

EPI is the result of an insufficient production of digestive enzymes by the exocrine pancreas. The exocrine pancreas also synthesizes and secretes the intrinsic factor (a protein) in dogs and cats. The intrinsic factor helps transport cobalamin (vitamin B12) throughout the body.

Under the strict definition of EPI, the intrinsic factor should not be affected by the condition because it is not a digestive enzyme. However, recent studies suggest that the intrinsic factor may be “impaired”.

EPI has an accompanying secondary condition called small intestinal dysbiosis (SID), which is located in the upper portion of the small intestine such as the duodenum. SID may contribute to cobalamin depletion.

EPI should be ruled out with the Trypsin-Like Immunoreactivity (TLI) test before diagnosing a CE.

All CEs are a bit more enigmatic compared to EPI. So, why would dogs or cats with a CE – but not EPI – have a vitamin B12 deficiency? Research suggests that dogs with CE have decreased expression of the cubam receptor, which is a multi-ligand receptor that specializes in absorption of vitamin B12 in the distal ileum.

Vitamin B12 Supplementation

For years and still to this day, the common protocol is to bypass the intestinal system altogether and inject Vitamin B12 directly into the bloodstream intravenously, subcutaneously or intramuscularly. Injections are usually completed by a veterinary clinic on a weekly basis. This, of course, eats up time and money.

Over the past five years or so, research has shown that daily oral supplementation to be just as effective as parenteral.

Of course, nothing is that simple.

Case in point, vitamin B12 is a water-soluble vitamin, which means the excess is excreted through the kidneys and toxicity should not occur. However, we want to make sure the body is effectively absorbing the vitamin supplement.

For instance, EPI4Dogs has years of trial and error experience with vitamin B12 supplementation. The organization finds that dogs that suffer from EPI do best with oral methylcobalamin.

Remember, the organization suggests “methylcobalamin”. Injectables and some oral supplements are cyanocobalamin.

The difference is cyanocobalamin is synthetic while methylcobalamin is natural B12.

In addition, EPI4Dogs suggests that intrinsic factor should be mixed into the oral methylcobalamin for dogs with EPI.

Please remember that intrinsic factor appears to be impaired in dogs and cats with EPI – not in dogs and cats with CE. So, dogs and cats with CE probably would not benefit from its addition.

First Round of Treatment Is a Test

So, can a veterinarian start vitamin B12 supplementation prior to diagnostic testing? While having a baseline is preferable, starting cobalamin without the test is not a problem. Particularly if the companion dog or cat will be able to thrive sooner and faster.

The test after first round of cobalamin treatment is arguably more important than baseline.

According to Texas A&M University’s Gastrointestinal Laboratory (TAMU), oral cobalamin treatment should be given daily for approximately three months. Then, supplementation is stopped for four weeks before testing. The EPI4Dogs non-profit suggests stopping for one week prior to testing, because stopping this important vitamin for longer can be harmful.

For parenteral, TAMU recommends weekly injections for 6 weeks, then one dose a month later, and retesting one month after the last dose.

Why should supplementation be discontinued prior to the test, although preferably for a short time? Basically, we want to find out how well the body absorbed and retained the cobalamin.

If the serum cobalamin concentration is high within, or above, the reference range and the underlying disease process has resolved for the time being, cobalamin can be discontinued according the TAMU.

We do not want dogs or cats below or within mid-normal range. So, cobalamin supplementation may continue and the delivery method – injection or oral – may need to be changed.

Supplementation may be reinstituted for dogs or cats with CE. For dogs with EPI, supplementation will more than likely be lifelong.

An accompanying test, serum methylmalonic acid (MMA), can be used as a marker for cobalamin deficiency on a cellular level. When MMA is high, this indicates a cobalamin deficiency at the cellular level.


A 2022 study by Chang et al. illustrates our point that the underlying disease causing the cobalamin deficiency can affect the type of supplement and its absorption at the cellular level.

This study had two sets of dogs: dogs with CE and dogs with EPI.

Dogs in both groups were split again between injectable cyanocobalamin and oral cyanocobalamin without the intrinsic factor.

The difference was interesting between the two groups.

Dogs with CE had significant decreases in serum MMA concentrations no matter the type of supplementation. On the other hand, dogs with EPI that were given oral cobalamin had significant decreases in these same concentrations.


Cobalamin for dogs and cats can be purchased without a prescription. However, we prefer that you work with your veterinarian to check blood levels and to ensure your companion pet is on the type of supplement and dosage.


Chang, Chee-Hoon et al. “Effect of oral or injectable supplementation with cobalamin in dogs with hypocobalaminemia caused by chronic enteropathy or exocrine pancreatic insufficiency.” Journal of veterinary internal medicine vol. 36,5 (2022): 1607-1621. doi:10.1111/jvim.16528,

Cridge, Harry et al. “Exocrine pancreatic insufficiency in dogs and cats.” Journal of the American Veterinary Medical Association vol. 262,2 246-255. 9 Nov. 2023, doi:10.2460/javma.23.09.0505,

Dodds, Jean. Chronic Enteropathy in Dogs: A Review & Interesting Research, Hemopet, 6 Aug. 2023,

Dodds, Jean. “Exocrine Pancreatic Insufficiency in Dogs and Cats.” Pet Health Resource, Tumblr, 14 May 2016,

Kather, Stefanie et al. “Review of cobalamin status and disorders of cobalamin metabolism in dogs.” Journal of veterinary internal medicine vol. 34,1 (2020): 13-28. doi:10.1111/jvim.15638,

“Managing EPI.” Epi4Dogs, Accessed 4 Feb. 2024.

Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS), Texas A&M University, 29 Jan. 2024,

Toresson, L et al. “Oral Cobalamin Supplementation in Dogs with Chronic Enteropathies and Hypocobalaminemia.” Journal of veterinary internal medicine vol. 30,1 (2016): 101-7. doi:10.1111/jvim.13797,

Toresson, Linda et al. “The Intestinal Microbiome in Dogs with Chronic Enteropathies and Cobalamin Deficiency or Normocobalaminemia-A Comparative Study.” Animals: an open access journal from MDPI vol. 13,8 1378. 17 Apr. 2023, doi:10.3390/ani13081378,

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