An evaluation of plasma homocysteine in the assessment of vitamin B12 status of pasture-fed sheep

Abstract

AIM: To assess the diagnostic potential of concentrations of homocysteine (Hcy) in plasma in relation to those of methylmalonic acid (MMA) and vitamin B12, as predictors of responsiveness of young sheep to supplementation with vitamin B12. METHODS: Eighty-two ewes grazing ryegrass-white clover pasture were used, 39 of which had been supplemented with a Co bullet and 43 unsupplemented. Thirty days after commencement of parturition their lambs (n=53 and 59, respectively) were randomly allocated into one of two treatments, in a 2 × 2 factorial design. Half of the lambs from each group of ewes received an injection of vitamin B12, while the remainder were controls. The trial commenced 31 October 2001 (Day 0), and continued until 01 May 2002 (Day 182). All lambs were weighed, and blood samples taken from 16 identified animals from each treatment group, at approximately monthly intervals. Changes in concentrations of Hcy, vitamin B12 and MMA in plasma, and liveweight gain (LWG) of the treatment groups were evaluated during the suckling (Days 0–89) and post-weaning (Days 90–182) periods. RESULTS: Mean LWG was 40% greater in supplemented than unsupplemented lambs. The concentrations of vitamin B12 and MMA in plasma in the unsupplemented lambs were in the deficient reference ranges of <170 pmol/L and >16 µmol/L, respectively. Mean monthly concentrations of Hcy in plasma ranged from 1.5 to 4.5 µmol/L but showed no pattern of response to vitamin B12 deficiency or supplementation. CONCLUSIONS: Measurement of the concentration of Hcy in plasma as a metabolic indicator of reduced methylation capability of sheep on typical pastures in New Zealand appeared to have little value in detection of vitamin B12 responsiveness, and was less sensitive than the concentration of the vitamin itself or the indicator of adenosyl-cobalamin deficiency, MMA, in plasma. The possibility that concentrations of Hcy in plasma remain low due to re-methylation of Hcy to methionine via the alternative betaine-choline rather than the vitamin B12-dependent methyl-tetrahydrofolate metabolic pathway is rejected, but the possibility is raised that high rates of trans-sulphuration of Hcy to cysteine in the gastrointestinal tract of grazing sheep could be responsible. CLINICAL RELEVANCE: The propionate-succinate pathway appears to be the first rate-limiting pathway in vitamin B12 deficiency, and the product of disruption of this pathway, increased MMA, is the most reliable indicator of metabolic abnormality in predicting responsiveness to supplementation.