Kempf J, Hersberger M, Melliger RH, Reusch CE, Kook PH. Effects of 6 Weeks of Parenteral Cobalamin Supplementation on Clinical and Biochemical Variables in Cats with Gastrointestinal Disease. J Vet Intern Med. 2017 Nov;31(6):1664-1672.
Cobalamin (vitamin B12) has been discussed extensively in this blog in the past as a major player in the diagnosis and therapy of intestinal disease in cats. Absorption of cobalamin is a complex process that requires normal pancreatic and intestinal function. Cobalamin stores are subject to extensive enterohepatic recirculation, leading to rapid depletion when significant intestinal (especially ileal) disease is present. This has led to the use of serum cobalamin levels as a diagnostic aide in cats with suspected GI disease, as well as the use of parenteral cobalamin supplementation to manage clinical signs.
While cobalamin levels are a useful tool, they do not always reflect clinical deficiency. In human medicine the assessment of homocysteine and methylmalonic acid (MMA) levels are used to determine if there are physiologic effects of cobalamin deficiency present. These chemicals are usually metabolized by cobalamin dependant pathways, and so become elevated when cobalamin levels are low. Homocysteine has been shown to be a less reliable indicator of B12 deficiency than MMA in cats, and has significant pre-analytic difficulties in assessment.
The purpose of this study was to determine if a standard protocol of cobalamin supplementation was able to normalize cobalamin and MMA levels, and clinical signs in cats with gastrointestinal disease. The study was designed as a prospective non-placebo controlled interventional trial. Cats received 250ug of cobalamin intramuscularly once weekly for 6 weeks, then a final dose 30 days after that.
Cats presenting to a teaching hospital were eligible for the study if GI signs existed and serum cobalamin was below the reference range (<224 pmol/L). Cobalamin was measured in 543 cats, of whom 201 were below the reference range. Of these, 48 were enrolled in the study and 20 completed it with a full dataset. Median age was 14 years and a variety of breeds were represented. Most cats presented with weight loss, other signs included vomiting, diarrhea, lethargy, and anorexia. Cats in the study received treatment with a variety of medications including corticosteroids, probiotics, chlorambucil, antibiotics, and methimazole.
Samples of serum and urine were collected before the first cobalamin injection and immediately frozen for later MMA assessment. Serum and urine samples were also collected before the 6th injection and 4 and 10 weeks after the 6th injection for measurement of serum cobalamin concentrations and frozen for MMA assessment. Clinical disease activity scores were assessed at each time point as well.
Clinical disease scores decreased significantly during cobalamin supplementation. Median cobalamin increased from 111pmol/L to 2332.5 pmol/L over the course of supplementation. Serum MMA levels decreased from 372umol/L to 1.62umol/L. By 4 weeks after the last cobalamin dose, cobalamin had fallen to 610pmol/L, and by 10 weeks 180.5pmol/L. At 4 weeks, serum MMA concentration was 5.34umol/L and by 10 weeks 189umol/L. By the time of the last cobalamin dose, 12 cats still had elevated MMA levels.
Urine MMA levels were also assessed. While there was a similar trend in urine MMA compared to serum MMA, this was not statistically significant.
The authors conclude that, in cats with GI disease, a 6 week course of B12 supplementation is likely insufficient to normalize levels in the long term.
This study had several limitations, including small sample size and the variety of comorbidities and types of intestinal diseases present. While attaining larger sample sizes and stratification into specific disease states would be difficult, it would be desirable in further research. Work should also be done into determining how cobalamin status changes when underlying disease states are treated.
Despite some limitations, this paper successfully demonstrated that cats with GI disease respond favorable to B12 supplementation, and that they likely require longer term cobalamin supplementation than 6 weeks. Measurement of serum MMA levels is a reasonable choice for assessment of cobalamin deficiency. (MRK)