grade the R proteins, releasing B12 to bind with intrinsic factor. The resulting complex of intrinsic factor and B12 attaches to specific receptors in the ileal mucosa; after internalization of the complex, B12 enters the enterocyte. Approximately 3 to 4 hours later, B12 enters the circulation. All circulating B12 is bound to the plasma binding proteins—transcobalamin I, II, or III (TCI, TCII, or TCIII). Although TCI binds approximately 80 percent of the B12 carried in the blood, TCII is the form that delivers B12 to the tissues through specific receptors for TCII (Hall and Finkler, 1966; Seetharam and Alpers, 1982). The liver takes up approximately 50 percent of the B12 and the remainder is transported to other tissues.
If there is a lack of intrinsic factor (as is the case in the condition called pernicious anemia), malabsorption of B12 results; if this is untreated, potentially irreversible neurological damage and life-threatening anemia develop.
The average B12 content of liver tissue is approximately 1.0 µg/g of tissue in healthy adults (Kato et al., 1959; Stahlberg et al., 1967). Estimates of the average total-body B12 pool in adults range from 0.6 (Adams et al., 1972) to 3.9 mg (Grasbeck et al., 1958), but most estimates are between 2 and 3 mg (Adams, 1962; Adams et al., 1970; Heinrich, 1964; Reizenstein et al., 1966). The highest estimate found for an individual’s total body B12 store was 11.1 mg (Grasbeck et al., 1958). Excretion of B12 is proportional to stores (see “Excretion”).
Studies to measure the actual absorption of B12 involve wholebody counting of radiolabeled B12, counting of radiolabeled B12 in the stool, or both. No data are available on whether B12 absorption varies with B12 status, but fractional absorption decreases as the oral dose is increased (Chanarin, 1979). Total absorption increases with increasing intake. Adams and colleagues (1971) measured fractional absorption of radiolabeled cyanocobalamin and reported that nearly 50 percent was retained at a 1-µg dose, 20 percent at a 5-µg dose, and just over 5 percent at a 25-µg dose. The second of two doses of B12 given 4 to 6 hours apart is absorbed as well as the first (Heyssel et al., 1966). When large doses of crystalline B12 are ingested, up to approximately 1 percent of the dose may be absorbed by mass action even in the absence of intrinsic factor (Berlin et al., 1968; Doscherholmen and Hagen, 1957).