Assessment of vitamin B12 status
Measurement of plasma concentrations of vitamin B12 is the method of choice, and several simple and reliable radioligand binding assays have been developed. A serum concentration of vitamin B12 below 110 pmol/l is associated with megaloblastic bone marrow, incipient anemia, and myelin damage. Below 150 pmol/l there are early bone marrow changes, abnormalities of the deoxyuridine monophosphate (dUMP) suppression test and methylmalonic aciduria after a valine load.
The absorption of vitamin B12 can be determined by the Schilling test. An oral dose of [57Co] or [58Co]-vitamin B12 is given with a parenteral flushing dose of 1 mg of non-radioactive vitamin to saturate body reserves, and the urinary excretion of radioactivity is followed as an index of absorption of the oral mate-rial. Normal subjects excrete 16–45% of the radioac-tivity over 24 h, whereas patients lacking the intrinsic factor excrete less than 5%.
The test can be repeated, giving the intrinsic factor orally together with the radioactive vitamin B12; if the impaired absorption was due to a simple lack of intrinsic factor, and not to anti-intrinsic factor anti-bodies in the saliva or gastric juice, then a normal amount of the radioactive material should be absorbed and excreted.
Methylmalonyl-CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl-CoA arising in the catabolism of isoleu-cine, cholesterol, and (rare) fatty acids with an odd number of carbon atoms. Normally, it undergoes vitamin B12-dependent rearrangement to succinyl-CoA, catalyzed by methylmalonyl-CoA mutase. Vitamin B12 deficiency leads to an accumulation of methylmalonyl-CoA, which is hydrolyzed to methyl-malonic acid, which is excreted in the urine. Urinary excretion of methylmalonic acid, especially after a loading dose of valine, provides a means of assessing vitamin B12 nutritional status.