Lion's Mane (Hericium erinaceus): Effects on Neurotrophic Factors and Cognitive Function

Introduction

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Lion’s Mane (Hericium erinaceus), also known as Yamabushitake in Japanese, is an edible medicinal mushroom traditionally used in Chinese and Japanese folk medicine to improve cognitive function and overall health [1]. This mushroom belongs to the Hericiaceae family and grows on dead or dying hardwood trees in temperate zones of North America, Europe, and Asia [2].

Historically, H. erinaceus was used in traditional Chinese medicine for treating gastrointestinal diseases and as a general tonic, but in the last two decades the scientific community has focused attention on its potential neuroprotective and cognitive-enhancing properties [3]. Interest in this mushroom increased significantly after the discovery of its ability to stimulate the synthesis of neurotrophic factors, which are critical for the growth, differentiation, and survival of neurons [4].

Bioactive Compounds

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Erinacines and Hericenones

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The main bioactive compounds in H. erinaceus that attract researchers’ attention are:

Erinacines — cyathane-type diterpenoids extracted primarily from the mushroom mycelium. To date, erinacines A-K have been identified, with erinacine A being the most studied compound [5]. Erinacines are low-molecular-weight compounds (molecular mass ~400-500 Da) capable of crossing the blood-brain barrier [6].

Hericenones — aromatic compounds extracted from the mushroom fruiting bodies. Hericenones A-H have been identified, also demonstrating neurotrophic activity, but to a lesser extent than erinacines [7].

Polysaccharides — including β-glucans (β-1,3-glucans and β-1,6-glucans), which possess immunomodulatory and neuroprotective properties [8]. Polysaccharides from H. erinaceus stimulate macrophage activity and increase the number of CD4+ cells and NK cells [9].

Biosynthesis Mechanisms and Compound Distribution

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CRITICAL INFORMATION: A recent study by Doar et al. (2025), published in Fungal Biology and Biotechnology, demonstrated fundamental differences in erinacine biosynthesis between mycelium and fruiting body [10]. Key findings:

1. Fruiting body produces virtually no erinacines — expression of eri genes (responsible for erinacine biosynthesis) was significantly suppressed in the fruiting body compared to mycelium, especially in the early stages of the biosynthetic pathway [10].

2. Mycelium is the primary source of erinacines — erinacine biosynthesis was substantially higher in mycelium both in gene expression and compound concentration [10].

3. Substrate critically affects erinacine profile — complex nutrient medium produced mycelium with significantly higher erinacine C content, while minimal medium led to higher erinacine Q content, indicating a shift in the biosynthetic pathway depending on substrate composition [10].

This data is critical for consumers: most commercial supplements from H. erinaceus fruiting bodies do not contain significant amounts of erinacines, which are considered the main compounds responsible for neurotrophic effects.

Bioavailability and Absorption

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A study of the absolute bioavailability of erinacine S showed that after oral administration of H. erinaceus mycelium extract (equivalent to 50 mg/kg erinacine S), bioavailability was 15.13% [11]. The primary site of absorption is the stomach, and the primary route of excretion is feces [11].

Erinacines and hericenones are low-molecular-weight compounds potentially capable of crossing the blood-brain barrier [6]. In bioassays using mouse astroglial cells, the volume of NGF secreted into the medium in the presence of erinacines was higher than with hericenones [12]. Intake with fatty food increases erinacine bioavailability [12].

Nerve Growth Factor (NGF) and BDNF

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Stimulation Mechanism

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Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) are members of the neurotrophin family, critically important for the growth, differentiation, and survival of neurons [13]. Decreased levels of NGF and BDNF are associated with neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease [14].

Erinacines and hericenones stimulate NGF synthesis in astrocytes and other glial cells through activation of signaling pathways, including the mTOR (mammalian target of rapamycin) pathway and TrkA (tropomyosin receptor kinase A) [15]. A systematic review included results from five randomized controlled trials (RCT), three pilot controlled trials, and fifteen laboratory studies, providing extensive evidence of the link between the neurotrophin protein family (NGF and BDNF) and diterpenoids (erinacines A, B, and C) extracted from H. erinaceus mycelium [16].

In vitro vs in vivo Data

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In vitro studies:

• Erinacines A-I demonstrate stimulation of NGF secretion in astroglial cell cultures at concentrations of 0.1-10 μg/mL [17].
• Hericenones C-H also stimulate NGF, but to a lesser extent [7].
• H. erinaceus polysaccharides increase expression of NGF and BDNF genes in neuronal cells [18].

In vivo studies:

• In mice receiving H. erinaceus mycelium extract enriched with erinacine A, NGF levels in the hippocampus increased by 27-43% compared to the control group [19].
• Administration of erinacine S to rats led to increased BDNF expression and activation of the BDNF-mTOR signaling pathway, which correlated with increased levels of synaptic proteins (p-GluA1, PSD95, synapsin-1) and stimulation of neurogenesis [20].
• H. erinaceus promotes oligodendrocyte maturation with increased expression of myelin basic protein, indicating potential in treating demyelinating diseases [21].

⚠️ WARNING: Although in vitro data demonstrate convincing stimulation of NGF and BDNF, extrapolation to the human organism requires caution. Concentrations effective in vitro may not be achieved in the human brain with oral administration due to limited bioavailability (15.13%) [11].

Clinical Studies

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Cognitive Function in the Elderly

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Mori et al. (2009) study [22] — landmark double-blind placebo-controlled study:

• Design: 30 participants aged 50-80 years with mild cognitive impairment (MCI), divided into two groups of 15 people each.
• Dosage: 4 tablets of 250 mg (96% H. erinaceus dry powder) three times daily (total 3 g/day) for 16 weeks.
• Results: At 8, 12, and 16 weeks, the H. erinaceus group showed significantly higher scores on the cognitive function scale (Revised Hasegawa Dementia Scale, HDS-R) compared to the placebo group.
• Limitations: Scores in the H. erinaceus group significantly decreased at 4 weeks after discontinuation, indicating a temporary rather than permanent effect.
• Safety: Laboratory tests revealed no adverse effects.

Recent 2025 study — 49-week pilot double-blind placebo-controlled study in patients with mild Alzheimer’s disease [23]:

• Dosage: H. erinaceus mycelium enriched with erinacine A (1.05 g/day).
• Results:
  • The H. erinaceus group showed significant improvement in homocysteine levels.
  • The placebo group showed a significant increase in amyloid-beta levels, while the H. erinaceus group showed no such increase, indicating a potential ability to slow neurodegenerative processes.
  • Significant improvement in Mini-Mental State Examination (MMSE) scores in the EAHE group and significant difference in Instrumental Activities of Daily Living scores between the two groups [23].

Acute Effects on Cognition and Mood

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2025 study — double-blind randomized placebo-controlled study of acute effects of standardized H. erinaceus extract in young healthy adults [24]:

• Design: Single dose of standardized extract vs. placebo.
• Results: The study demonstrated positive effects on cognition and mood with acute (single) administration.
• Significance: Indicates that H. erinaceus effects may manifest not only with long-term intake but also in the short term.

Depression and Anxiety

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Clinical studies in humans with depression and anxiety have shown some positive results, although data are limited. In one study, 30 postmenopausal women who consumed cookies containing H. erinaceus (2 g/day) for 4 weeks demonstrated reduced symptoms of irritability and anxiety compared to the placebo group [25].

Alzheimer’s Disease and Neurodegeneration

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Preclinical data:

• Erinacine A-enriched H. erinaceus mycelium reduced the number of amyloid plaques (Aβ-plaques) and total plaque burden in APPswe/PS1dE9 transgenic mice (Alzheimer’s disease model) [26].
• At the molecular level, H. erinaceus reduced β-amyloid accumulation, aberrant APP overexpression, phosphorylated Tau, and activation of NLRP3 inflammasome components [26].
• The level of insulin-degrading enzyme (IDE) in the brain cortex of APP/PS1 mice receiving H. erinaceus increased by more than 127% compared to wild-type control group, which additionally affected Aβ-plaque burden [26].

Clinical data: As mentioned above, the 49-week study in patients with mild Alzheimer’s disease demonstrated slowing of neurodegeneration progression by biomarkers (amyloid-beta, homocysteine) and cognitive tests [23].

Dosages and Forms

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⚠️ WARNING: Differences Between Forms

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Fruiting body:

• Traditional form used in food and powder supplements.
• Contains hericenones but virtually no erinacines [10].
• Clinical studies with fruiting body used doses of 0.75-5 g/day [22, 25].

Mycelium:

• Primary source of erinacines [10].
• Standardized preparations enriched with erinacine A.
• Clinical studies with mycelium used doses of 1.05-3 g/day mycelium equivalent [23].

Extracts:

• Concentrated preparations with standardization for erinacine or hericenone content.
• Dosages range from 500 mg to 3000 mg/day depending on active compound concentration [27].
• Standardization problem: Many commercial products do not specify erinacine or hericenone content, making it difficult to assess efficacy.

Recommended Dosages

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Based on clinical studies and systematic reviews [27]:

• Fruiting body powder: 0.75-3 g/day (divided into 2-3 doses).
• Mycelium enriched with erinacine A: 1-1.05 g/day.
• Extracts: Up to 3000 mg/day for adults as a practical upper limit in consumer supplements.

⚠️ WARNING: Exceeding tolerable doses of H. erinaceus typically causes mild, self-limiting symptoms, most often affecting the gastrointestinal tract, and sometimes mood or sleep [28].

Safety and Side Effects

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Safety Profile

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H. erinaceus is generally recognized as safe (GRAS) and is not associated with increased liver enzymes during therapy or episodes of clinically apparent liver injury [29]. Studies of short-term H. erinaceus therapy in humans have reported minor adverse effects and scant evidence of toxicity [27].

In clinical studies of long-term therapy, mild gastrointestinal complaints (abdominal discomfort, nausea, or diarrhea) were typically reported in fewer than 10% of patients and generally did not require discontinuation [27].

Studies in rats revealed no adverse effects even at doses up to 2.3 g/pound (5 g/kg) body weight per day for 1 month [30].

⚠️ Contraindications and Precautions

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Allergy: Anyone with an allergy or sensitivity to mushrooms should avoid H. erinaceus, as cases of difficulty breathing or skin rashes after exposure have been reported [28].

Blood clotting disorders: H. erinaceus has demonstrated anticoagulant properties. If you have a blood clotting disorder and are taking anticoagulants, you should avoid H. erinaceus supplements [28].

Pregnancy and breastfeeding: There is insufficient reliable information about the safety of using H. erinaceus during pregnancy or breastfeeding. It is recommended to abstain from use [28].

Autoimmune diseases: H. erinaceus may activate the immune system, which could worsen symptoms of autoimmune diseases such as multiple sclerosis, lupus, and rheumatoid arthritis. It is recommended to avoid use in the presence of these conditions [28].

Hypersensitivity: At least one case of acute hypersensitivity reaction to oral H. erinaceus has been described [27].

Criticism and Research Limitations

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Small Sample Sizes

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Most clinical studies of H. erinaceus have small samples (15-30 participants per group) [22, 25], which limits statistical power and the ability to generalize results to a broader population.

Protocol Heterogeneity

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Studies use different:

• Forms of preparation (fruiting body vs. mycelium vs. extracts).
• Dosages (from 0.75 to 5 g/day).
• Intervention durations (from 4 to 49 weeks).
• Assessment methods (various cognitive scales).

This heterogeneity makes it difficult to compare results and conduct meta-analyses.

Conflict of Interest

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Some studies are funded by H. erinaceus supplement manufacturers, creating a potential conflict of interest. For example, studies conducted in collaboration with companies producing mushroom supplements may be biased toward positive results [31].

Lack of Long-Term Data

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Most studies have an observation period of no more than 16 weeks, with one exception at 49 weeks [23]. Long-term effects (>1 year) and safety with prolonged use remain insufficiently studied.

Unclear Active Compounds

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Although erinacines and hericenones are considered the main active compounds, the exact mechanism of action and relative contribution of different components (erinacines, hericenones, polysaccharides, other bioactive substances) to clinical effects remain not fully clear.

[UNVERIFIED] Temporary Effects

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The Mori et al. (2009) study showed that cognitive function improvement disappears 4 weeks after discontinuation [22], raising questions about the need for continuous intake to maintain effects and the mechanisms of long-term neuroprotection.

Conclusion

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Hericium erinaceus represents a promising neurotrophic compound with proven ability to stimulate NGF and BDNF synthesis in vitro and in vivo. Clinical studies demonstrate potential efficacy in improving cognitive function in people with mild cognitive impairment and in slowing neurodegenerative processes in Alzheimer’s disease.

Key Conclusions:

1. Mycelium > Fruiting body: For neurotrophic effects, preparations from mycelium enriched with erinacines are preferable to fruiting body powder [10].

2. Bioavailability is limited: Oral bioavailability of erinacines is approximately 15%, which may limit efficacy [11].

3. Effects are temporary: Cognitive function improvement may disappear after discontinuation [22].

4. Safety: Safety profile is favorable with short-term and medium-term use, but long-term data are limited [27, 29].

5. Further research needed: Large-scale randomized controlled trials with long observation periods, standardized protocols, and independent funding are required.

H. erinaceus is not a “miracle cure” for cognitive enhancement, but represents a promising component of a comprehensive approach to maintaining brain health, especially in elderly people with early signs of cognitive decline. Consultation with a physician is mandatory before starting intake, especially for people with mushroom allergies, blood clotting disorders, or autoimmune diseases.

Sources

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[1] PMC (2024). Benefits, side effects, and uses of Hericium erinaceus as a supplement: a systematic review. https://pmc.ncbi.nlm.nih.gov/articles/PMC12434001/

[2] PMC (2025). Lion’s Mane Mushroom (Hericium erinaceus): A Neuroprotective Fungus with Antioxidant, Anti-Inflammatory, and Antimicrobial Potential—A Narrative Review. https://pmc.ncbi.nlm.nih.gov/articles/PMC12030463/

[3] Restorative Medicine. Lion’s mane (Hericium erinaceus). https://restorativemedicine.org/library/monographs/lions-mane/

[4] PMC (2018). Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines. https://pmc.ncbi.nlm.nih.gov/articles/PMC5987239/

[5] Frontiers (2025). Unveiling the role of erinacines in the neuroprotective effects of Hericium erinaceus: a systematic review in preclinical models. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1582081/full

[6] PMC (2021). Hericium erinaceus mycelium and its small bioactive compounds promote oligodendrocyte maturation with an increase in myelin basic protein. https://www.nature.com/articles/s41598-021-85972-2

[7] Journal of Natural Products (2024). Uncovering Hericenones from the Fruiting Bodies of Hericium erinaceus through Interdisciplinary Collaboration. https://pubs.acs.org/doi/10.1021/acs.jnatprod.4c01018

[8] PMC (2018). Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines. https://pmc.ncbi.nlm.nih.gov/articles/PMC5987239/

[9] PMC (2025). Lion’s Mane Mushroom: A Neuroprotective Fungus. https://pmc.ncbi.nlm.nih.gov/articles/PMC12030463/

[10] Doar et al. (2025). Influences of substrate and tissue type on erinacine production and biosynthetic gene expression in Hericium erinaceus. Fungal Biology and Biotechnology. https://fungalbiolbiotech.biomedcentral.com/articles/10.1186/s40694-025-00194-9

[11] PMC (2019). Absolute Bioavailability, Tissue Distribution, and Excretion of Erinacine S in Hericium erinaceus Mycelia. https://pmc.ncbi.nlm.nih.gov/articles/PMC6514545/

[12] Restorative Medicine. Lion’s mane bioavailability. https://restorativemedicine.org/library/monographs/lions-mane/

[13] Cambridge Core (2024). Hericium erinaceus: A possible future therapeutic treatment for the prevention and delayed progression of Alzheimer’s disease? https://www.cambridge.org/core/journals/nutrition-research-reviews/article/hericium-erinaceus-a-possible-future-therapeutic-treatment-for-the-prevention-and-delayed-progression-of-alzheimers-disease-a-narrative-review/4520BA4AD6E32081BE96D90266DF98DA

[14] PMC (2023). Hericium erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond. https://pmc.ncbi.nlm.nih.gov/articles/PMC10218917/

[15] PMC (2018). Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines. https://pmc.ncbi.nlm.nih.gov/articles/PMC5987239/

[16] PMC (2024). Benefits, side effects, and uses of Hericium erinaceus as a supplement: a systematic review. https://pmc.ncbi.nlm.nih.gov/articles/PMC12434001/

[17] Frontiers (2025). Unveiling the role of erinacines in neuroprotective effects. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1582081/full

[18] ScienceDirect (2024). Bioactive substances in Hericium erinaceus and their biological properties: a review. https://www.sciencedirect.com/science/article/pii/S2213453024000715

[19] PMC (2016). Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1dE9 transgenic mice. https://pmc.ncbi.nlm.nih.gov/articles/PMC4924315/

[20] PMC (2018). Neurohealth Properties of Hericium erinaceus Mycelia. https://pmc.ncbi.nlm.nih.gov/articles/PMC5987239/

[21] Nature (2021). Hericium erinaceus mycelium promotes oligodendrocyte maturation. https://www.nature.com/articles/s41598-021-85972-2

[22] Mori et al. (2009). Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. PubMed. https://pubmed.ncbi.nlm.nih.gov/18844328/

[23] Frontiers (2020). Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study. https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00155/full

[24] Frontiers (2025). Acute effects of a standardised extract of Hericium erinaceus on cognition and mood in healthy younger adults. https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1405796/full

[25] ResearchGate. Outcomes of clinical trials of H. erinaceus. https://www.researchgate.net/figure/Outcomes-of-clinical-trials-of-H-erinaceus_tbl3_321969743

[26] Journal of Biomedical Science (2016). Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies. https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-016-0266-z

[27] PMC (2024). Benefits, side effects, and uses of Hericium erinaceus as a supplement: a systematic review. https://pmc.ncbi.nlm.nih.gov/articles/PMC12434001/

[28] Drugs.com. Lion’s Mane Mushroom Uses, Benefits & Dosage. https://www.drugs.com/npp/lion-s-mane-mushroom.html

[29] NCBI Bookshelf. Lion’s Mane - LiverTox. https://www.ncbi.nlm.nih.gov/books/NBK599740/

[30] Healthline. 9 Health Benefits of Lion’s Mane Mushroom (Plus Side Effects). https://www.healthline.com/nutrition/lions-mane-mushroom

[31] Mushroom Clinical Trials. Lions Mane (Hericium erinaceus). https://mushroomclinicaltrials.com/lions-mane-hericium-erinaceus/

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