Lion’s Mane and Nerve Growth Factor: Tracing the Claim to Its Source

“Lion’s Mane stimulates nerve growth factor” is one of the most repeated claims in the mushroom world. It is usually stated as a settled fact about what the mushroom does in people. This article follows the claim back to the laboratory papers it comes from, looks at what each one actually tested, and explains why the picture is less tidy than the slogan.

What nerve growth factor is

Nerve growth factor, or NGF, is a protein that helps certain nerve cells grow and survive. It was discovered in the 1950s by Rita Levi-Montalcini and Stanley Cohen, who shared a Nobel Prize for the work in 1986. NGF is a large molecule that doesn’t pass easily from the blood into the brain, so researchers have long been interested in smaller compounds that might prompt cells to make more of their own. That search is the background to the Lion’s Mane story.

The papers, one by one

Kawagishi et al., 1991 (Japan). Hirokazu Kawagishi and colleagues isolated three new compounds from the fruiting body of Lion’s Mane (Hericium erinaceus) and named them hericenones C, D and E. When the purified compounds were added to mouse astroglial cells, a type of support cell from the brain, grown in culture, the researchers reported that the cells released more NGF into the surrounding liquid. In 1994 the same group reported a second family of compounds, the erinacines, from the mycelium, and described them as stronger stimulators in the same kind of test. See Hericenones Explained and Erinacines Explained.

These were chemistry papers. They established that the compounds exist, worked out their structures, and showed an effect when purified material was placed directly onto mouse cells. They did not involve whole mushroom, digestion, animals or people.

Mori et al., 2008 (Japan). Seventeen years later, a different group tested alcohol extracts of four edible mushrooms on a human cell line called 1321N1. Only the Lion’s Mane extract increased the activity of the NGF gene, and it did so more strongly at higher concentrations. But when the researchers tested purified hericenones C, D and E on the same cells, the compounds did not increase NGF gene activity. The authors concluded that the extract contains something that stimulates NGF production in these cells, and that the active compounds are not hericenones. In a short second experiment, mice fed dried Lion’s Mane powder for seven days showed more NGF gene activity in the hippocampus, a brain region involved in memory.

This paper is often cited in support of the NGF claim, and it does support part of it. It also contradicts the commonest version, in which hericenones are named as the reason. Several of its authors also appear on the 2009 human trial described in Lion’s Mane Research: What Does the Evidence Actually Show?

Martínez-Mármol et al., 2023 (Australia and South Korea). This study, led from the Queensland Brain Institute, attracted wide press coverage. The researchers tested Lion’s Mane compounds on nerve cells taken from the hippocampus of rats and grown in culture. Two compounds, known as NDPIH and hericene A, promoted the growth of long projections from these cells. Male mice fed a crude Lion’s Mane extract or hericene A then performed better on a memory test based on recognising a new object. The authors proposed that the compounds act through a signalling pathway shared by several growth factors, not through NGF alone.

It is a detailed piece of laboratory work, and it moved the conversation on from NGF to a wider family of growth factors. It was carried out in cultured cells and in male mice. Headlines saying Lion’s Mane had been “found to boost memory” left out the word mice.

Reading the three papers together

• The named compound keeps changing. Hericenones in 1991, “not hericenones” in 2008, hericene A and NDPIH in 2023. That is normal in science, but it means the confident naming of one active compound on a product page is not supported.
• Different cells give different answers. Mouse astroglial cells, a human cell line and rat nerve cells are three separate test systems. An effect in one did not carry over to another.
• Direct contact is not digestion. In every cell experiment the compound was placed straight onto the cells. Nothing was swallowed, absorbed or broken down. See What Is Bioavailability?
• Fruiting body and mycelium differ. Erinacines come mainly from the mycelium, so findings about them say little about fruiting body products. See Lion’s Mane Fruiting Body vs Mycelium.
• Nobody has measured it in people. The human trials of Lion’s Mane measured scores on thinking and memory tests. None measured NGF in the brain, which can’t be done in living volunteers.

A chain of inference

The claim as usually made joins several steps together: a compound raises NGF in cultured cells, so the mushroom raises NGF in the body, so it raises NGF in the brain, so it changes how the brain works. The laboratory papers address the first step, with mixed results. The mouse experiments touch on the second and third. The last step has not been shown. See Correlation, Mechanism and Causation in Mushroom Research.

What we can reasonably conclude

Lion’s Mane contains unusual compounds, and extracts of it have changed growth-factor activity in cultured cells and in mice in several independent laboratories. That makes it a reasonable subject for further research. It does not show that Lion’s Mane products raise nerve growth factor in people, and no health claims are authorised for Lion’s Mane in the UK.

What remains uncertain

• Which compounds in Lion’s Mane are responsible for the effects seen in cells.
• Whether those compounds reach the brain in people after being swallowed, and in what amounts.
• Whether any change in growth factors would lead to a difference a person could notice.

Our approach

We make our Lion’s Mane tincture from UK-grown fruiting bodies and describe it by what it is and how it’s made, not by what it might do. For the wider picture, see The Complete Guide to Lion’s Mane.

References

1. Kawagishi H, Ando M, Sakamoto H, et al. Hericenones C, D and E, stimulators of nerve growth factor (NGF)-synthesis, from the mushroom Hericium erinaceum. Tetrahedron Letters. 1991;32(35):4561–4564.
2. Kawagishi H, Shimada A, Shirai R, et al. Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum. Tetrahedron Letters. 1994;35(10):1569–1572.
3. Mori K, Obara Y, Hirota M, et al. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biological and Pharmaceutical Bulletin. 2008;31(9):1727–1732.
4. Martínez-Mármol R, Chai Y, Conroy JN, et al. Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. Journal of Neurochemistry. 2023;165(6):791–808.

Study titles are reproduced as published and are not claims made by Spore & Bloom.