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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
The following studies provide the basis for the estimate used in Step 1. These studies do not provide ideal data on which to base an EAR, but they bracket the requirement by providing values that are obviously too low or too high to meet the needs of 50 percent of the individuals in an age group.
Studies of Patients with Pernicious Anemia. Darby and coworkers (1958) studied the effects of various intramuscular (IM) doses of B12 in 20 subjects with pernicious anemia who had not previously been treated or who were in relapse. The diagnosis of pernicious anemia had been based on the clinical history and on the findings of macrocytic anemia, megaloblastic hyperplasia of bone marrow, histamine-fast achlorhydria, and a negative radiological examination of the gastrointestinal tract. These diagnoses were not made based on results of the Schilling test, first published as a method in 1953 (Schilling, 1953). The extent of the disease differed among the subjects; 14 had neurological manifestations. Of the 18 subjects who received doses of 1 µg/day of B12 or less for 2 weeks, 5 or fewer responded satisfactorily according to the standards used for erythrocytes (Isaacs et al., 1938) and reticulocytes (Isaacs and Friedman, 1938). At B12 dosages of less than 0.5 µg/day, no patient met those standards. Dosages used for maintenance were increased to 1 to 4 µg/day for a period of months to years. MCVs greater than 100 were considered macrocytic. No reticulocyte counts or serum B12 values were reported. According to the authors’ interpretation, the data indicated that subjects achieved and maintained maximum erythropoiesis as indicated in Table 9-5. Approximately half (4 of 7) did so at a B12 intake of 1.4 µg/day IM.
TABLE 9-5 Effectiveness of Intramuscular Vitamin B12 Doses for Maintenance of Maximum Erythropoiesis
Daily B12 Dose, Intramuscular (µg)
Number of Subjects Achieving Maximum Erythropoiesis (n = 7)
Cumulative Number Achieving Maximum Erythropoiesis (n = 7)