What we left out.
The ingredients with the best story in this category tend to have the weakest human proof. Here is what that means, and why three famous mushrooms are not in the bottle.
Beat the
benchmark,
not the
baseline.
Most supplement studies report that the people who took the ingredient improved compared to their own starting point. That proves almost nothing.
The placebo group usually improves too, because people get better at cognitive tests simply by taking them a second time. It is called the practice effect, and it is large enough to produce a flattering chart on its own. The only result that counts is a between-group difference, where the ingredient group beat the placebo group.
It is the same distinction a portfolio manager lives by. Showing that your number went up is not performance. The index went up too. Performance is what you did relative to the benchmark.
Applied to a supplement aisle, that one filter removes most of it.
01 Lion's mane Not included
Marketed for memory, focus and nerve growth. The exciting nerve growth factor mechanism comes from petri dishes and mice. The human cognitive trials are few and small, the between-group results are mixed or null, and the most-cited trial has an abstract claiming a cognitive benefit that its own results section does not support statistically.
Mechanism: Mori et al., Biological & Pharmaceutical Bulletin 31(9), 2008 — nerve growth factor expression in cultured human astrocytoma cells; Brandalise et al., Evidence-Based Complementary and Alternative Medicine 2017, article 3864340 — recognition memory in wild-type mice. Human trials: Mori et al., Phytotherapy Research 23(3), 2009 — 30 adults aged 50 to 80 with mild cognitive impairment over 16 weeks, the most-cited of them; Grozier et al., International Journal of Exercise Science 15(2), 2022 — 24 healthy young adults over four weeks, no effect on cognition.
02 Cordyceps Not included
Marketed for energy and clean stimulation. No human randomised trial shows cordyceps improves memory, attention or executive function against placebo. The best-powered cognition trial found no effect. Its real human evidence is in aerobic endurance, and even there it is modest, mixed, and skewed toward older untrained participants.
Cognition: Tsuk et al., International Journal of Medicinal Mushrooms 19(8), 2017 — 96 healthy young adults, 30 days, randomised and placebo-controlled; no difference on memory, attention, executive function or processing speed. Endurance: Chen et al., Journal of Alternative and Complementary Medicine 16(5), 2010 — 20 untrained adults aged 50 to 75, ventilatory threshold improved over 12 weeks; against Parcell et al., International Journal of Sport Nutrition and Exercise Metabolism 14(2), 2004 — no effect in 22 trained cyclists over five weeks.
03 Reishi Not included
Marketed for calm, sleep and clarity. The only randomised placebo-controlled trial measuring cognition found no advantage over placebo, and no trial has tested reishi for attention or memory in healthy adults at all. An interesting botanical with a real traditional history, but the human evidence for focus does not exist yet.
Cognition: Tsuk et al., International Journal of Medicinal Mushrooms 19(8), 2017 — 96 healthy young adults, 30 days, no difference across any cognitive domain; the supplement paired reishi with cordyceps, so reishi on its own is still untested for attention or memory. Tang et al., Journal of Medicinal Food 8(1), 2005 — 132 people with neurasthenia over eight weeks, but the outcomes were fatigue and wellbeing, not cognition.
These are not scams. They are stories that outran their evidence. We like some of them fine. They are just not in a product whose whole argument is that its ingredients cleared the benchmark.