David B Miller BVSc Hons MMedVet[Med] Johannesburg Specialist Veterinary Centre, Johannesburg, South Africa
Cobalamin (vitamin B12) is an essential water-soluble vitamin and is a co-factor for many biochemical reactions. Canine and feline diets contain enough cobalamin, so dietary insufficiency does not occur. Absorption of cobalamin is complex and requires a healthy digestive system. Cobalamin is bound to dietary protein. After partial digestion in the stomach it is released and immediately binds to R-binder protein synthesised by the gastric mucousa. In the small intestine the R-binder protein is digested by pancreatic enzymes and free cobalamin now binds to intrinsic factor (IF), which is mainly secreted by the pancreas absorption occurs in the ileum. Diseases that interfere with cobalamin uptake (secondary cobalamin malabsorption) include excessive bacterial utilization of cobalamin associated with bacterial dysbiosis (bacterial overgrowth), exocrine pancreatic insufficiency (EPI), longstanding and severe intestinal disease (IBD, lymphoma) affecting the small intestine in dogs but is seen even with mild GI signs in cats. Chronic severe disease of the ileum may lead to destruction or reduced expression of the IF receptors on enterocytes causing malabsorption. Deficiency occurs when stores are depleted – thus indicating a chronic condition. Exocrine pancreatic insufficiency results in a lack of pancreatic proteases to separate cobalamin from R-protein. EPI is a major cause of hypocobalaminaemia and B12 levels MUST be checked in these cases. IF bound cobalamin is also bound by anaerobic bacteria and thus made unavailable for absorption as they compete. Thus bacterial overgrowth will cause a decrease. In these cases folate will often be increased as some bacteria synthesize folate. The estimated biological half-life of cobalamin in dogs is 50–100 days. Low serum cobalamin, reflects failing GI cobalamin absorption and a chronic condition. Veterinary laboratories are able to measure cobalamin and the test is not expensive. Primary (inherited) GI cobalamin malabsorption occurs when gene mutation causes cobalamin malabsorption. These disorders are uncommon but breed-specific and present as poor doers with anaemia and low white cell counts. Giant schnauzers, Beagles, Border Collies, Australian Shepherds, and Chinese Shar-Peis may have a genetic defect.
Deficiencies cause abnormalities in the metabolism of the haematological, neurological or gastrointestinal systems, as well as poor response to treatment for gastrointestinal disease. Clinical signs are generally non-specific and vary depending on the age of the patient, the severity of deficiency and the duration of the condition. Clinical signs are also often mixed with the other signs caused by the primary condition. In young and growing animals there is a chronic, relapsing inappetence, lethargy, and failure to thrive and gain weight and there might also be chronic diarrhoea and/or intermittent vomiting. Seizures may occur if diagnosis and treatment are delayed. In adult animal signs are usually mild until sufficiently longstanding to alter mucosal function.
Measurement and/or supplementation of serum cobalamin concentrations in animals with GI disease is important as failure to recognize a deficiency will result in delayed clinical recovery as untreated cobalamin deficiency will lead to progressive megaloblastic and megalocytic changes of the intestinal epithelium that in turn cause generalized malabsorption. Thus chronic intestinal disease of whatever cause may not be successfullly treated until cobalamin stores are replenished by parenteral administration. It is shown that low serum cobalamin concentrations are a risk factor for negative outcome in dogs with chronic enteropathies. Appetite often returns to normal within 12–24 hours, and weight gain occurs over the following weeks. A reticulocyte response will typically occurs 3–4 days post-administration, and there is often a similar burst of neutrophil production. Red blood cell and neutrophil numbers normalize in 2–3 weeks. I treat all dogs with low B12 levels BUT I treat all cats with levels from mid range downwards as cats are more prone to B12 deficiencies. Dosages for injectable cobalamin are as follows:
For cobalamin deficiency: 250 µg (per cat) SC once per week for 6 weeks, then every 1-2 months based on cobalamin levels or 250 µg SC injection weekly for 6 weeks; then one injection every 2 weeks for 6 weeks; then monthly injections for the patient’s whole life.2
For cobalamin deficiency – Injectable cyanocobalamin at 25 µg/kg, or practically, 250 – 1200 µg per dog (based on dog’s size) SC once per week for 4-6 weeks, then every 14 days for 4-6 weeks, then monthly thereafter to maintain normal serum levels. May take as long as 3-4 weeks to see a response and lifelong therapy may be required depending on the status of underlying cause.
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