because they do not predict the ultimate completeness or maintenance of response.

The reticulocyte count is a useful measure of hematological response because an increase is apparent within 48 hours of B₁₂ administration and reaches a peak at 5 to 8 days.

The concentration of B₁₂ in the serum or plasma reflects both the B₁₂ intake and stores. The lower limit is considered to be approximately 120 to 180 pmol/L (170 to 250 pg/mL) for adults but varies with the method used and the laboratory conducting the analysis. As deficiency develops, serum values may be maintained at the expense of B₁₂ in the tissues. Thus, a serum B₁₂ value above the cutoff point does not necessarily indicate adequate B₁₂ status (see the section “Vitamin B₁₂ Deficiency”) but a low value may represent a long-term abnormality (Beck, 1991) or prolonged low intake.

The range that represents expected variability (2 standard deviations) for serum MMA is 73 to 271 nmol/L (Pennypacker et al., 1992). The concentration of MMA in the serum rises when the supply of B₁₂ is low. Elevation of MMA may also be caused by renal failure or intravascular volume depletion (Stabler et al., 1988), but Lindenbaum and coworkers (1994) reported that moderate renal dysfunction in the absence of renal failure does not affect MMA values as strongly as does inadequate B₁₂ status. MMA values tend to rise in the elderly (Joosten et al., 1996); in most cases this appears to reflect inadequate B₁₂ intake or absorption. Lindenbaum and coworkers (1988) reported that elevated serum MMA concentrations are present in many patients with neuropsychiatric disorders caused by B₁₂ deficiency. Pennypacker and colleagues (1992) found that intramuscular injections of B₁₂ reduced the elevated MMA values in their elderly subjects. The reduction of elevated MMA values with B₁₂ therapy has also been reported in other studies (Joosten et al., 1993; Naurath et al., 1995; Norman and Morrison, 1993). Increased activity of anaerobic flora in the intestinal tract may increase serum MMA values; treatment with antibiotics decreases the serum MMA concentration in this situation (Lindenbaum et al., 1990). Because the presence of elevated concentrations of MMA in serum represents a metabolic change that is highly specific to B₁₂ deficiency, the serum MMA concentration is a preferred indicator