op. The progression of neurological manifestations is variable but generally gradual. Whether neurological complications are reversible after treatment depends on their duration. The neurological complications of B₁₂ deficiency occur at a later stage of depletion than do the indicators considered below and were, therefore, not used for estimating the requirement for B₁₂. Moreover, neurological complications are not currently amenable to easy quantitation nor are they specific to B₁₂ deficiency.

B₁₂ deficiency is also frequently associated with various gastrointestinal complaints, including sore tongue, appetite loss, flatulence, and constipation. Some of these complaints may be related to the underlying gastric disorder in pernicious anemia.

Search of the literature revealed numerous indicators that could be considered as the basis for deriving an Estimated Average Requirement (EAR) for vitamin B₁₂ for adults. These include but are not limited to hematological values such as erythrocyte count, hemoglobin concentration or hematocrit, and mean cell volume (MCV), blood values such as plasma B₁₂, and the metabolite methylmalonic acid (MMA).

Measurements used to indicate a hematological response that could be considered as indicative of B₁₂ sufficiency have consisted of either a minimal but significant increase in hemoglobin, hematocrit, and erythrocyte count; a decrease in MCV; or an optimal rise in reticulocyte number.

In the earliest studies, MCV was a calculated value that was derived from relatively imprecise erythrocyte counts. Although MCV is now directly measured and precise, the response time of this measurement to changes in dietary intake is slow because of the 120-day longevity of erythrocytes. Consequently, the MCV is of limited usefulness. The erythrocyte count, hemoglobin, and hematocrit values are all robust measurements of response. Again, however, the response time is slow before an improvement in B₁₂ status leads to a return to normal values. Partial responses are of limited value