Research

Erinacine A: what the research shows

A review of the published human and preclinical literature on erinacine A-enriched Hericium erinaceus mycelium. What the trials found, and what they did not.

What erinacine A is

A diterpenoid produced by the mycelium of Hericium erinaceus, the lion's mane mushroom. Erinacines were first identified in the 1990s as stimulators of nerve growth factor synthesis. Erinacine A is the most studied of the group.

Why mycelium, not fruiting body

Hericenones come from the fruiting body. Erinacines come from the mycelium. They are different molecules. Culinary fruiting bodies contain little to no erinacine A, which is why a lion's mane you cook with is not a source of it.

Why liquid culture, not grain

Standardized erinacine A requires submerged liquid fermentation followed by HPLC verification. Grain-grown mycelial biomass is largely the substrate the fungus was grown on. If a product cannot show a lab sheet for its erinacine A content, there is no way to know what is in it.

The clinical trials

Li 2020 — 49 weeks, double-blind, placebo-controlled

Frontiers in Aging Neuroscience 12:155 · NCT04065061

Population. Adults over 50 with a diagnosis of probable mild Alzheimer's disease.

Material and dose. Grape King Bio liquid-culture mycelium, freeze-dried, standardized to 5 mg/g erinacine A. Three 350 mg capsules daily: 1,050 mg mycelium, 5.25 mg erinacine A per day.

What was reported. The placebo group declined significantly on the CASI. The active group improved significantly on the MMSE. Instrumental activities of daily living differed significantly between the two groups. Contrast sensitivity was significantly better in the active group. On serum markers, the significant changes appeared in the placebo group: falls in calcium, albumin, APOE4, hemoglobin and BDNF, and rises in alpha1-antichymotrypsin and amyloid-beta 1-40. The active group showed no significant change from baseline on those markers.

Safety. Four participants withdrew for abdominal discomfort, nausea and skin rash. Overall adverse-event incidence was 8.2% over 49 weeks.

Limitations. This was a pilot study. The authors describe the result as suggesting the material "may be important in achieving neurocognitive benefits." The marker pattern is best read as an absence of decline in the active group rather than a reversal in it. The finding has not been independently replicated.

Chan 2022 — 8 months, double-blind, placebo-controlled

Journal of Functional Foods 97:105220 · NCT03632512

Population. 80 adults aged 50 to 79 with symmetric sensorineural hearing loss, recruited from a hospital ear, nose and throat department.

Material and dose. Same production method and standardization as Li 2020. Eight honey boluses daily, each containing 250 mg freeze-dried mycelium: 2,000 mg mycelium, 10 mg erinacine A per day.

What was reported. Across all participants, there was no significant difference between groups on any hearing measure, or on BDNF or NGF. In the subgroup aged 65 and over, significant differences appeared in high-frequency hearing thresholds in both ears, all-frequency threshold in the left ear, speech recognition threshold in both ears, and serum NGF.

Safety. Hematology and biochemistry stayed within reference ranges, with no significant differences between groups.

Limitations. The primary analysis was null. The positive findings are a subgroup result. 21 of 80 participants, 26%, were lost to follow-up. The placebo was maize starch rather than a matched mushroom material, so participants who noticed a difference in taste could have been unblinded.

The healthy-adult trial

Cernelič Bizjak 2024 · Journal of Functional Foods 115:106120

Population. 33 healthy adults over 55, excluding chronic disease, neurodegenerative disease, brain injury and stroke.

Material and dose. An erinacine A-enriched preparation at 3.44 mg erinacine A per day for 8 weeks. The material was supplied by MycoMedica, Slovenia, and grown on a substrate with part of the harvest extracted and recombined. It is not Grape King mycelium and not the material in NeuraLegend Core.

What was reported. A cognitive-speed difference and a BDNF difference between groups, along with changes in gut microbiota composition.

Limitations. n=33 pilot. The cognitive-speed result reached significance only after adjustment for baseline score, age, sex and a gut marker. The authors attribute part of the BDNF difference to a decline in the placebo group and note possible seasonal variation. The placebo was corn starch rather than a matched mushroom material.

What the research does not show

  • No trial has established that erinacine A treats, prevents or reverses any disease.
  • Neither of the two larger trials has been independently replicated.
  • Both of those trials used starch placebos rather than matched mushroom material, which weakens blinding.
  • The trials that used the material in NeuraLegend Core were conducted in clinical populations. The trial conducted in healthy adults used a different material.
  • The preclinical work below is in animals and cell models. It is hypothesis-generating, not clinical evidence.

Preclinical findings

  • Erinacine A increased nerve growth factor content in the locus coeruleus and hippocampus of rats after oral dosing (Shimbo 2005).
  • Erinacines were originally isolated as NGF-synthesis stimulators from Hericium erinaceus mycelium (Kawagishi 1994, 1996).
  • Oral Hericium erinaceus mycelium reduced cochlear impairment in senescence-accelerated SAMP8 mice, with raised neurotrophic expression in spiral ganglion neurons and reduced outer hair cell damage (Hwang 2020).
  • Erinacine A-enriched mycelium modulated BDNF/PI3K/Akt/GSK-3beta signalling in a mouse model (Chiu 2018).
  • Hericium erinaceus mycelium promoted oligodendrocyte maturation with increased myelin basic protein (Huang 2021).

How this relates to ErinaPrime

ErinaPrime is a freeze-dried, liquid-culture Hericium erinaceus mycelium from Grape King Bio, standardized to 1% erinacine A. Both Li 2020 and Chan 2022 used the same manufacturer, the same submerged liquid-culture process, and the same lyophilized mycelium, standardized to 0.5%. ErinaPrime is standardized to 1%, twice that concentration.

At one capsule, ErinaPrime delivers 5 mg erinacine A per day, comparable to the Li 2020 dose. At two capsules, it delivers 10 mg per day, the Chan 2022 dose.

References

  • Cernelič Bizjak M, et al. Effect of erinacine A-enriched Hericium erinaceus supplementation on cognition: a randomized, double-blind, placebo-controlled pilot study. J Funct Foods 2024;115:106120.
  • Chan Y-C, et al. Effects of erinacine A-enriched Hericium erinaceus on elderly hearing-impaired patients: a double-blind, randomized, placebo-controlled clinical trial. J Funct Foods 2022;97:105220.
  • Chiu C-H, et al. Erinacine A-enriched Hericium erinaceus mycelium produces antidepressant-like effects through modulating BDNF/PI3K/Akt/GSK-3beta signaling in mice. Int J Mol Sci 2018;19(2):341.
  • Huang H-T, et al. Hericium erinaceus mycelium and its small bioactive compounds promote oligodendrocyte maturation with an increase in myelin basic protein. Sci Rep 2021;11:1.
  • Hwang J-H, et al. Hericium erinaceus mycelium prevents cochlear impairment in senescence-accelerated mice. 2020.
  • Kawagishi H, et al. Erinacines E, F and G, stimulators of nerve growth factor synthesis, from the mycelia of Hericium erinaceum. Tetrahedron Lett 1996;37(41):7399-7402.
  • Li I-C, et al. Prevention of early Alzheimer's disease by erinacine A-enriched Hericium erinaceus mycelia pilot double-blind placebo-controlled study. Front Aging Neurosci 2020;12:155.
  • Shimbo M, Kawagishi H, Yokogoshi H. Erinacine A increases catecholamine and nerve growth factor content in the central nervous system of rats. Nutr Res 2005;25(6):617-623.

These statements have not been evaluated by the Food and Drug Administration. NeuraLegend products are dietary supplements and are not intended to diagnose, treat, cure, or prevent any disease. This page reviews published research on an ingredient. It is not a product claim.