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Without intrinsic factor, the small intestine cannot efficiently absorb dietary B12 through the normal receptor-mediated pathway

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A 2025 JAMA Neurology trial (n=1,500) demonstrated a 15-20% reduction in Hamilton Depression Rating Scale (HDRS) scores in deficient adults (serum B12 200 pg/mL and methylmalonic acid (MMA) 0.4 mol/L), with higher doses compensating for poor absorption or severe symptoms like megaloblastic anemia and neuropathy

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J Virol 81:66906699 Reddy MS, Chen F, Shadle G, Jackson L, Aljoe H, Dixon RA (2005) Targeted down-regulation of cytochrome P450 enzymes for forage quality improvement in alfalfa ( Medicago sativa L.)