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SERUM VITAMIN B12 (CYANOCOBALAMIN/COBALAMIN) AND FOLATE FOR EVALUATING INTESTINAL FUNCTION

SERUM VITAMIN B12 (CYANOCOBALAMIN/COBALAMIN) AND FOLATE FOR EVALUATING INTESTINAL FUNCTION

In dogs and cats with unexplained weight loss or chronic small intestinal diarrhoea, serum vitamin B12 and folate concentrations may be useful to evaluate intestinal absorptive function. But don’t forget, that many factors can affect their concentrations, thus those tests are not specific and definitive diagnosis cannot be made based on them only.

Exposure to light may falsely decrease cobalamin concentration and haemolysis may falsely increase folate concentration.

SERUM VITAMIN B12

Cobalamin is released from dietary protein by pepsin and gastric acid in the stomach and then binds to R protein. This complex passes into the small intestine, where it is digested by pancreatic proteases. Anew released cobalamin binds to the intrinsic factor (produced by gastric mucosa in dogs and pancreas in dogs and cats) and the complex is finally absorbed in the distal small intestine, mainly ileum.

Main causes for decreased cobalamin concentrations:

  • Small intestinal bacterial overgrowth (SIBO): intestinal bacteria bind cobalamin, preventing its absorption.
  • Exocrine pancreatic insufficiency (EPI): lack of pancreatic proteases which would release B12 from the R proteins or decreased intrinsic factor production (especially in cats – they lack gastric intrinsic factor). EPI can also secondary lead to SIBO.
  • Diseases damaging ileal mucosa: decreased absorption of cobalamin. Underlying diseases can be many types of inflammatory bowel disease and neoplasia (alimentary lymphoma).

Congenital cobalamin malabsorption has been documented in border collies, giant schnauzers, Australian shepherds, beagles and shar peis.

Cobalamin is required as a cofactor for DNA and protein synthesis and all tissues need it for optimal function, thus, cobalamin deficiency can lead to more severe clinical signs. If a deficiency is documented, parenteral supplementation with cobalamin is recommended for the optimal response to treatment of the underlying GI disease.

Increased levels of cobalamin are relatively uncommon but may occur with high dietary intake or parenteral supplementation.

SERUM FOLATE

Folate is ingested in the form of folate polyglutamate, which is deconjugated to monoglutamate in the proximal small intestine by folate deconjugase enzyme. Monoglutamate is than absorbed by specific folate carriers in the proximal intestine, especially jejunum. Folate is also produced by many different enteric bacteria.

The main cause of decreased serum folate is proximal small intestinal disease, which reduces its absorption. Potential underlying causes are inflammatory bowel disease, infiltrative neoplasia, gluten enteropathy in Irish setters … Overuse of antibiotics can lead to the sterilization of the intestine and decreased serum folate.

Potential causes for increased folate concentrations include excess parenteral supplementation or high dietary intake and SIBO (folate production by bacteria). Greater folate absorption occurs at lower intestinal pH, which can be caused by excessive gastric acid secretion or decreased bicarbonate secretion (also seen with EPI).

INTERPRETATION OF VITAMIN B12 AND FOLATE CONCENTRATIONS

The results of the analysis are relevant only if the pancreatic function is normal and the condition is sufficiently chronic for body reserves of vitamin B12 and folate to have been depleted. A decrease in vitamin B12 with or without increased folate is suggestive of EPI, and TLI testing is indicated. Prolonged anorexia or vitamin supplements can each in a different way affect serum concentrations.

The combination of decreased vitamin B12 and increased folate concentrations with normal pancreatic exocrine function suggests SIBO, as many bacterial species synthesise folate and others bind cobalamin. SIBO is usually a sign of underlying intestinal disease rather than an independent diagnosis (may result secondary to EPI or many intestinal diseases that cause defects in the mucus barrier or decreased peristalsis), idiopathic cases of bacterial overgrowth are more appropriately described as antibiotic responsive diarrhoea (ARD). SIBO is rare condition in cats, low concentration of cobalamin is most frequently associated with small intestinal disease.

A decrease in the concentration of both, vitamin B12 and folate suggests severe, chronic disease involving the entire small intestine (generalized malabsorption). Both decreased values have also been reported in cats with EPI in addition to intestinal disease.

Decreased vitamin B12 concentration with normal folate and normal pancreatic function suggests distal small intestinal disease, whereas decreased folate with normal vitamin B12 suggests proximal small intestinal disease.

No disease should cause the rise of both – vitamin B12 and folate. In this case, B-complex vitamin supplementation before sampling is most likely.

LITERATURE:

Thrall M. A., Weiser G., Allison R. W., Campbell T. W.: Veterinary Hematology and Clinical Chemistry, 2nd Ed. Wiley-Blackwell, 2012

Hall E. J., Simpson J. W., Williams D. A.: BSAVA Manual of Canine and Feline Gastroenterology, 2nd Ed. BSAVA, 2005