of B12 status. However, data were not sufficient to use MMA as the criterion on which to base the EAR in this report. Serum MMA values from older studies may not be comparable with those obtained recently because of improvements of methods over time (Beck, 1991; Green and Kinsella, 1995). More importantly, no studies were found that examined directly the relationship of B12 intake and MMA concentrations.
Serum total homocysteine concentration is commonly elevated in elderly persons whose folate status is normal but who have a clinical response to treatment with B12 (Stabler et al., 1996). Because a lack of folate, vitamin B6, or both also results in an elevated serum and plasma homocysteine concentration, this indicator has poor specificity and does not provide a useful basis for deriving an EAR.
Although most patients with untreated B12 deficiency excrete an increased amount of formiminoglutamic acid (FIGLU) in the urine after an oral loading dose of histidine, FIGLU excretion is also almost invariably increased in folate deficiency as well. The test, therefore, lacks specificity for the diagnosis of either vitamin deficiency. Concentrations of propionate, the metabolic precursor of methylmalonate, also rise with B12 deficiency. Propionate may be converted to 2-methylcitrate, serum and cerebrospinal fluid concentrations of which also rise in B12 deficiency (Allen et al., 1993). However, the measurement of either propionate or methyl citrate offers no advantages over serum MMA for the detection of B12 deficiency.
Among the three plasma B12 binding proteins, transcobalamin II (TCII) is responsible for receptor-mediated uptake of B12 into cells. However, only a small fraction of the plasma B12 (10 to 20 percent) is present as the TCII-B12 complex. This fraction, termed holoTCII, may provide a good indication of B12 status, and methods have been described to measure this fraction (Herzlich and Herbert, 1988; Vu et al., 1993). These methods are currently considered to be insufficiently robust for routine clinical use.