Lion's Mane

Where the story comes from

Hericium erinaceus looks like a white mop, is called yamabushitake in Japan and has been eaten as an edible mushroom in East Asia for centuries. The research history begins in 1991 in Japan: the natural product chemist Kawagishi isolates 3 molecules from the fruiting body, names them hericenones C, D and E, and shows that they stimulate the production of nerve growth factor in cell culture.

NGF is a protein that keeps certain nerve cells alive, above all the cholinergic neurons that are lost early in Alzheimer's disease. Hence the reflex: if a mushroom upregulates NGF, perhaps it protects against dementia. In 1994 the same group finds a second class of compounds in the mycelium, the network of threads from which the mushroom grows — the erinacines, considerably more potent in cell culture. The fruiting body has hericenones, the mycelium has erinacines.

The active ingredient is not established

In 2008 a group at Tohoku University repeated the cell experiment on human astrocytoma cells. Mushroom extract added, NGF goes up — that was confirmed. Then they tested the pure hericenones C, D and E individually, and they had no effect. The authors state, in essence: the active substances are not the hericenones.

This does not call the mechanism into question, but its attribution: the extract does something in the dish, what exactly is open. Of all things, the molecule on which the labeling of many packages is based did not work in the very test on which that labeling rests.

What has been shown in animals

Mice with mushroom powder in their feed had more NGF messenger in the hippocampus after 7 days. Mice that are injected with amyloid in the brain lose less memory on mushroom feed. And erinacine A from the mycelium demonstrably reaches the brain in rats, with a peak after 8 hours.

This matters particularly because NGF itself does not cross the blood-brain barrier: Alzheimer's researchers had to pump it directly into patients' brain ventricles or implant genetically modified cells into the forebrain. A mushroom that gets the brain to make NGF itself would be elegant. Evidence that NGF rises in the human brain, or even just in the blood, is however missing entirely.

The question of the package

Hericenones are found in the fruiting body, erinacines in the mycelium. The Taiwanese Alzheimer's study used standardized mycelium with 5 milligrams of erinacine A per gram, the Japanese studies fruiting body powder. Many packages, by contrast, say only: extract — without stating from which part and how much of what.

Mycelium is often grown on grain and then everything is ground together. Without a certificate of analysis, the buyer does not know whether they are rebuilding the preparation from Taiwan, the one from Japan, or one that does not appear in any study.

What the studies show

Mori 2009, mild cognitive impairment, Japan

30 participants between 50 and 80 years of age, 15 per group, 16 weeks of 4 tablets of fruiting body powder 3 times daily, around 3 grams daily. From week 8 the mushroom group was significantly better on a Japanese dementia scale, and the gap grew until week 16; 4 weeks after stopping, the scores fell again. The first author works in the mushroom laboratory of Hokuto Corporation.

Saitsu 2019, healthy people over 50, Japan

31 evaluable participants over 50 without a diagnosis, 12 weeks, 3.2 grams of fruiting body powder daily, randomized and double-blind. Of 3 tests, only one was significant, the Mini-Mental State Examination; no difference in memory for pictures and for word pairs. The Mini-Mental test is coarse, designed for dementia screening; nothing can be found on the funding.

Li 2020, mild Alzheimer's dementia, Taiwan

The longest study: 49 weeks double-blind, 49 randomized, 41 completed, with mycelium containing 5 milligrams of erinacine A per gram, 3 capsules daily. The placebo group declined on the screening test, the mushroom group improved on the Mini-Mental test, with a difference in everyday function in favor of the mushroom. 6 of the 10 authors are employed by Grape King Bio. 4 participants dropped out because of abdominal discomfort, nausea and skin rash.

Docherty 2023, young healthy people, United Kingdom

41 adults between 18 and 45 years of age, 1.8 grams. 60 minutes after a single dose they were faster on the Stroop test, p equal to 0.005. After 28 days only a trend toward less perceived stress, p equal to 0.051, plus null findings and some slightly negative results. The authors themselves call the work a pilot study.

Grozier 2022, students, USA

24 students, 10 grams daily baked into muffins, 4 weeks, single-blind. No effect, on any of the measured variables. 10 grams is more than three times the Japanese dose. Whether baking broke down the active compounds, nobody knows.

Nagano 2010, mood, Japan

30 women, 4 weeks, 4 cookies with mushroom powder daily. The depression score was lower after intake than before. Significant versus placebo were only 2 sub-items of a symptom questionnaire: palpitations and numbness.

What is missing in humans

The decisive measurement is missing. No human study has shown that lion's mane increases NGF in the blood or in the brain of humans. The neurogenesis story rests on cell culture and animals, and even there the active ingredient has not been identified.

The human basis is thin and skewed: 6 controlled studies, around 200 participants in total, the two most positive each from a manufacturer's own house. In the best-known one, the effect disappeared 4 weeks after stopping — an effect that goes with the last tablet is not nerve growth. The two studies in healthy people without a manufacturer at the helm turn out weaker. And on dementia there is exactly one study, in mild Alzheimer's dementia, in which the mushroom group declined less over almost a year. That needs to be repeated by someone who does not sell the mushroom.

Status, approval and legal

Lion's mane is sold as a food or food supplement. As a medicine it is not approved anywhere, so there is no standardization of its composition under medicines law. The study preparations differed considerably — standardized mycelium in Taiwan, fruiting body powder in Japan, whole mushrooms in muffins in the USA. A package that says only extract lacks this information.

Safety

Little is to be expected from an edible mushroom, and little has been reported. In the studies, abdominal discomfort, nausea and one case of skin rash occurred; in the Taiwanese study, 4 participants dropped out because of this. The American liver database LiverTox classifies lion's mane as an unlikely cause of liver injury and lists at least one case of an acute hypersensitivity reaction. Interactions with medicines have not been studied.

Sources

• Kawagishi et al., Tetrahedron Letters 1991
• Kawagishi et al., Tetrahedron Letters 1994
• Mori et al., Biol Pharm Bull 2008
• Mori et al., Phytother Res 2009
• Saitsu et al., Biomed Res 2019
• Li et al., Front Aging Neurosci 2020
• Docherty et al., Nutrients 2023
• Grozier et al., Int J Exerc Sci 2022