Understanding vitamin B12 absorption requires moving beyond the conventional model of a single absorption pathway. Current evidence demonstrates three critical points: first, intrinsic factor—the primary absorption mechanism—saturates at approximately 1.5 micrograms, creating an absolute ceiling regardless of dose. Second, passive diffusion, though typically inefficient at absorbing only 1–2% of any dose, becomes the functionally dominant route at high supplement concentrations. Third, a standard 1,000 microgram oral supplement delivers roughly 10 micrograms via passive diffusion alone, substantially exceeding the 2.4 microgram daily requirement.
These findings have immediate clinical relevance. For patients with pernicious anaemia, intrinsic factor deficiency, or gastrointestinal conditions limiting conventional B12 absorption, high-dose oral supplementation (500–1,000 micrograms) represents a non-invasive therapeutic option. While the NIH Office of Dietary Supplements recognizes this approach as an alternative to intramuscular injection, clinicians should note that injection remains first-line treatment. Individual patient factors—compliance, absorption capacity, and clinical response—should guide treatment selection.
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