NGF and BDNF each look after different neurons, but both are large proteins that cannot be taken orally or cross the directly.Nerve growth factor (NGF) governs survival, synapse maintenance, and myelination of basal forebrain cholinergic neurons — the hardware of memory and attention. BDNF leans toward hippocampal and prefrontal synaptic plasticity. Both are large proteins that cannot be taken orally and cannot cross the directly.
2 · Small molecules make the brain produce its own NGF
Hericenones and erinacines from this mushroom are small molecules that cross the and stimulate the brain to synthesize its own NGF.Lion's mane fruiting bodies contain hericenones; mycelium contain erinacines — these are small molecules that can cross the . They do not deliver NGF directly; they stimulate the brain to synthesize its own. In vitro studies show several-fold NGF secretion increases, but there is a huge gap between in vitro concentrations and in-brain levels after oral dosing.
3 · The five-step chain from molecule to cognition
The mushroom molecules cross the and stimulate brain cells to secrete NGF, which then binds TrkA on neurons, and in theory this improves cognition.The order is easy to get backwards, so here it is straight: hericenone/erinacine crosses the → stimulates brain cells to express and secrete NGF → NGF then binds TrkA on neurons (TrkA is NGF's own receptor; the mushroom molecules do not bind it) → the signal travels retrogradely to the soma → dendritic growth, synapse formation, myelin maintenance → theoretically improves cognition. Each step has experimental support, but the chain is only as strong as its weakest link — in humans, steps 1 (brain concentration) and 5 (cognitive measurement) are weakest.
4 · Human evidence: early candidate, not a miracle
In two small human trials the mushroom groups beat placebo on cognitive scales, but the trials used different products and doses, so it remains an early candidate.Mori 2009: 30 adults aged 50-80 with mild cognitive impairment, double-blind and placebo-controlled. The material was fruiting-body dry powder, four 250 mg tablets (1 g) three times a day — 3 g/day — for 16 weeks. Scores beat placebo at weeks 8, 12 and 16, but fell significantly again 4 weeks after stopping.
Li 2020: mild Alzheimer's, using erinacine A-enriched mycelium, three 350 mg capsules a day — about 1.05 g/day — for 49 weeks; 49 randomised, 41 completed. Between groups, only the daily-living scale IADL was significantly better than placebo; MMSE rose only within the mushroom group and did not differ significantly from placebo, and CASI showed no significant difference between the groups either. This was a pilot trial with a small sample.
Note that the two trials did not give people the same substance: one is fruiting-body powder, the other a mycelium extract, and the doses differ almost threefold. No single grams-per-day number follows from them — two jars both labelled lion's mane can contain quite different actives. Positioning: mechanistically plausible early candidate, not a proven nootropic.