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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.

Serum or Plasma Vitamin B12

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.

Methylmalonic Acid

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



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