Relationship of urinary methylmalonic acid to vitamin B-12 concentrations and hematologic changes in rats fed vitamin B-12-deficient diets
Brink, J.J.; Beck, R.A.; Miller, J.S.; Thenen, S.W.
Journal of Nutrition 110(7): 1338-1346
1980
ISSN/ISBN: 0022-3166 PMID: 7381597 Document Number: 157445
Urinary methylmalonic acid in vitamin B-12-deprived rats was studied. Rats on vitamin B-12-deficient purified diets for 10 months after weaning began to excrete methylmalonic acid above control values at 6 weeks. Growth retardation relative to control rats on vitamin B-12-supplemented diets was observed 3 weeks after deprivation and increased with time until 39 weeks when control rats were on average 29% heavier than deficient rats. Concentrations of vitamin B-12 in liver of rats on the deficient diet declined exponentially from weaning with a half-life of 13.6 weeks. Methylmalonate began to appear in urine when the liver vitamin B-12 concentration was nearly 84% of the initial value. Plasma vitamin B-12 concentrations also declined exponentially to undetectable values (below 0.05 ng/ml) after 27 weeks, having a half-life almost identical to that of liver vitamin B-12. Brain vitamin B-12 increased threefold above the weanling value in the initial 9 weeks and then declined exponentially, with a half-life of 10.3 weeks. Nuclear hypersegmentation of neutrophils characteristic of megaloblastic granulopoiesis was observed in bone marrow and peripheral blood of deficient rats having haematocrits less than 40% after 33 weeks of dietary treatment.