Understanding vitamin B12 absorption requires knowledge of two distinct physiological mechanisms that operate under different constraints. The primary pathway, mediated by intrinsic factor, is highly efficient but severely limited—it saturates at approximately 1.5 micrograms regardless of dose size. This ceiling explains why patients cannot simply increase intrinsic factor-dependent absorption through larger oral doses. The secondary mechanism, passive diffusion, operates without such constraints, absorbing 1-2% of any B12 amount consumed throughout the entire digestive tract. This means a 1,000 microgram supplement delivers roughly 10 micrograms via diffusion alone—sufficient to meet daily requirements even when the primary pathway is compromised. Clinicians should recognize that high-dose supplements function not through improved efficiency, but through activation of compensatory absorption mechanisms. This distinction informs patient selection, dosing strategies, and expectations for therapeutic outcomes. Read the full article on GMJ Newsroom.
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