Table 1.
Cobalamin numbers that are useful in understanding cobalamin physiology, depletion, and therapy in adults
| Normal absorption | Malabsorptive disease (eg, PA) | |
|---|---|---|
| Estimated daily loss/requirement | ∼ 1 μg/day | ∼ 2 μg/day* |
| Recommended daily allowance | 2.4 μg/day† | Supplements are required |
| Average body stores of cobalamin | ∼ 2500 μg | Depends on stage of depletion |
| Ratio of stores to daily losses | 2500:1 | ∼ 1200:1‡ |
| Amount (percentage) absorbed from a single oral dose of:§ | ||
| 1 μg | 0.56 μg (56%) | 0.01 μg (1.2%) |
| 10 μg | 1.6 μg (16%) | 0.1 μg (1.2%) |
| 50 μg | 1.5 μg (3%) | 0.6 μg (1.2%) |
| 500 μg | 9.7 μg (2%) | 7.0 μg (1.3%) |
| 1000 μg | ∼ 13 μg (1.3%) | ∼ 12 μg (1.2%) |
| Amount (percentage) retained from a single injection of:‖ | ||
| 10 μg | 9.7 μg (97%) | Same as normal |
| 100 μg | 55 μg (55%) | Same as normal |
| 1000 μg | 150 μg (15%) | Same as normal |
The data are summarized from the literature, especially from Chanarin1 and Berlin et al.16 However, individual variation is wide, both in normal persons and patients with malabsorption.
Daily losses presumably nearly double because of impaired reabsorption of biliary cobalamin in PA and other IF-related disorders (1.4 μg cobalamin is excreted in bile daily, of which half is presumably reabsorbed). The near-doubling of daily losses helps explain why deficiency progresses relatively more rapidly in PA than in disorders where IF-mediated reabsorption is preserved (eg, dietary insufficiency and, presumably, food-bound cobalamin malabsorption).
IF-mediated absorption is only 50% to 60% of a small dose (ie, a normal meal). Thus, 2.4 μg should provide the daily 1-μg requirement but fails if the IF system does not function.
This estimate applies at the onset of the malabsorptive process. As stores become depleted, daily losses also decrease, but these changes, including the ratios, have not been quantitated.
Based largely on data from Berlin et al.16 Note: (1) the reduced absorption rates in normal persons as oral doses escalate, (2) the constant 1.2% rate of nonspecific, IF-free cobalamin diffusion across the gut (clearly evident in patients with PA), and (3) the convergence of amounts of cobalamin absorbed by normal and malabsorbing persons the more oral doses exceed the capacity of IF.
Mean data compiled from Chanarin1 and others. Variation among individuals is wide, however.