Lion’s Mane – Hericium erinaceus

Japanese NameYamabushitake
Chinese NameHou Tou Gu (Monkey Head Mushroom)
English NameLion’s Mane Mushroom/Bearded Tooth Mushroom

This delicious mushroom has been referred to as ‘Nature’s Nutrient for the Neurons’ on account of its ability to stimulate the production of nerve growth factor (NGF)1,2. NGF plays an essential role in the differentiation and survival of several cell populations in the central and peripheral nervous system and lower than normal levels of NGF have been linked to early stages of both Alzheimer’s disease and dementia3-8.
Although therapeutic interest has largely focussed on its importance for neurological function, NGF plays a much wider role in maintaining homoeostasis in the body9,10. It is known to have insulinotropic, angiogenic, and antioxidant properties and reduced plasma levels of NGF have been associated with cardiovascular diseases and metabolic syndromes, including type 2 diabetes11,12. It has been shown to accelerate wound healing and there is evidence that it could be useful in the treatment of skin and corneal ulcers13. Animal studies have shown NGF to have a profound effect on airway inflammation and asthma-related symptoms with increased NGF levels observed in bronchoalveolar lavage fluid and serum from patients with asthma14.
NGF also has a dynamic relationship with the immune system. Generation of NGF is increased after brain injury, in part due to cytokines produced by immune cells.At the same time immune cells express receptors for NGF, which is involved in immune modulation15.
Two families of compounds from H. erinaceus have been identified as being active in the stimulation of NGF production: the aromatic hericenones (isolated from the fruiting body) and the diterpenoid erinacines (isolated from the mycelium). Critically these molecules are small enough to pass through the blood-brain barrier. There is also evidence that they can increase myelination1,16-18.
In China the mycelium is used to make H. erinaceus pills to treat gastric and duodenal ulcers, chronic gastritis, gastric and oesophageal cancer.

DEMENTIA – In controlled studies H. erinaceus supplementation showed beneficial effects in patients with mild dementia. In one study six out of seven patients showed improvement in functional capacity (understanding, communication, memory etc.) while all seven showed improved Functional Independence Scores (eating, dressing, walking etc.), after consuming 5g H. erinaceus fruiting body daily in soup for six months1.
In another study, 30 patients aged 50-80 with mild dementia were randomised into treatment and control groups. H. erinaceus was given as tablets at 3g/day for 16 weeks and produced significant increases in cognitive function in the treatment group. However, four weeks after the conclusion of the trial, cognitive function scores decreased indicating a need for continued supplementation17.

MSH. erinaceus fruiting body extract has been shown to improve the myelination process in mature myelinating fibres with possible benefits for MS patients18,19. NGF has also been shown to have a protective effect on axons and myelin by suppressing the immune-mediated inflammatory processes responsible for chronic brain destruction in neurodegenerative disorders such as MS by switching the immune response to an anti-inflammatory, suppressive mode in a brain-specific environment13.

NEUROPATHY – NGF plays a role in pain sensitivity and low NGF levels have been linked to sensory neuropathy in both in vivo and in vitro studies10. Enhanced NGF production has been shown to protect sensory function in diabetic rats and NGF reduction has been shown to cause cardiac sensory neuropathy21,22.
Clinical studies with recombinant human NGF indicate benefit in patients with diabetic polyneuropathy23 and NGF has also been reported to reduce pain in patients with HIV associated sensory neuropathy24,25. However, ability to promote regeneration of sensory neurons has yet to be demonstrated26,27.

NERVE DAMAGE – Rats given aqueous extract of H. erinaceus fruiting bodies showed faster recovery from nerve injury, suggesting potential for application of H. erinaceus in the early stages of nerve regeneration28-31.

ANXIETY / DEPRESSION – One study reports reduction in anxiety and depression from consumption of 2g/day (taken in cookies) and patients often report increased feelings of wellbeing when taking H. erinaceus, possibly due to the kappa opiod receptor agonist activity of the erinacines32,33.

MENOPAUSAL SYNDROME – Many patients report reduction in symptoms related to menopause and perimenopause, including sleep disturbance, anxiety and hot flushes (hot flashes) from consumption of H. erinaceus 3-5g/day d.w. although this is as yet unsupported by clinical research.

MRSA – Extracts of both fruiting body and mycelium exhibit anti-MRSA activity with erinacines identified as active compounds. In clinical tests in Japan MRSA is reported to have been cleared in a number of patients whose diet was supplemented with H. erinaceus34.

GASTRIC ULCERS – One of the traditional indications for H. erinaceus, it appears likely that the antibacterial action of the erinacines and hericenones contribute to its benefit in this regard, with Helicobacter pylori now known to be a major cause of gastric ulcers and chronic gastritis35-37.
A rat study on the effects of H. erinaceus aqueous extract on alcohol-induced ulcers showed a significant reduction of the ulcer area, as well as protection against gastric mucosa injury, while an in vitro study found that H. erinaceus extract was active against nine clinical strains of H. pylori with a 0.02% concentration having a 50% bactericidal activity38,39.

CLINICAL SUMMARY
Main Therapeutic Application – Dementia, Alzheimer’s disease, MS, nerve damage, menopausal synrome.
Key Component – Hericenones and erinacines.
Dose – Clinical trials support the use of dried fruiting body at a dose of 3-5g/day for increasing NGF production while animal studies on the use of H. erinaceus for gastric ulcers produced the best results with a daily intake of 500mg/kg, which equates to the dosage prescribed in the Chinese Phamacopoeia of 25-50g/day40. It is likely that similar doses would be required in cases of MRSA.
High in vitro NGF promoting activity of mycelial extracts and the fermentation broth also indicates potential for the use of mycelial biomass products41,42.
Caution – Asthma and other allergic conditions. Erinacine E is a potent agonist of the kappa opioid receptor with potential hallucinogenic properties33.

REFERENCES
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2. Erinacines E, F, and G, stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum. Kawagishi H, Shimada A, Hosokawa S, Mori H, Sakamoto H, Ishiguro Y, Sakemi S, Bordner J, Kojima N, Furukawa S. Tetra Lett. 1996;37(41):7399–7402.
3. Erinacine A increases catecholamine and nerve growth factor content in the central nervous system of rats. Shimbo M, Kawagishi H, Yokogoshi H. Nutr Res. 2005;25(6):617–623.
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9. The nerve growth factor and the neuroscience chess board. Levi-Montalcini R. Prog Brain Res. 2004;146:525–527.
10. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, Ghenev PI, Aloe L. Prog Brain Res. 2004;146:279–289.
11. Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L. Int J Cardiol. 2005;102(1):169–171.
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16. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Biol Pharm Bull. 2008;31(9):1727-1732.
17. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Phytother Res. 2009;23(3):367–372.
18. The influence of Hericium erinaceus extract on myelination process in vitro. Kolotushkina EV, Moldavan MG, Voronin KY, Skibo GG. Fiziol ZH. 2003;49(1):38–45.
19. Hericium erinaceus (Bull.: Fr.) Pers. extract effect on nerve cells. Grygansky AP, Moldavan MG, Kolotushkina OV, Kirchhoff B, Skibo GG. Int J Med Mushrooms. 2001;3(2-3):152.
20. Haploinsufficiency of the nerve growth factor beta gene in a 1p13 deleted female child with an insensitivity to pain. Fitzgibbon GJ, Kingston H, Needham M, Gaunt L. Dev Med Child Neurol. 2009;51(10):833–837.
21. Protection of sensory function in diabetic rats by Neotrofin. Calcutt NA, Freshwater JD, Hauptmann N, Taylor EM, Mizisin AP. Eur J Pharmacol. 2006;534(1-3):187–193.
22. Nerve growth factor is critical for cardiac sensory innervation and rescues neuropathy in diabetic hearts. Ieda M, Kanazawa H, Ieda Y, Kimura K, Matsumura K, Tomita Y, Yagi T, Onizuka T, Shimoji K, Ogawa S, Makino S, Sano M, Fukuda K. Circulation. 2006;114(22):2351–2363.
23. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA. Neurology. 1998;51(3):695–702.
24. Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy. Schifitto G, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, Marra CM, Rubin M, Cohen BA, Tucker T, Koralnik IJ, Katzenstein D, Haidich B, Smith ME, Shriver S, Millar L, Clifford DB, McArthur JC; AIDS Clinical Trials Group Team 291. Neurology. 2001;57(7):1313–1316.
25. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. McArthur JC, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, Marra C, Rubin M, Cohen BA, Tucker T, Navia BA, Schifitto G, Katzenstein D, Rask C, Zaborski L, Smith ME, Shriver S, Millar L, Clifford DB, Karalnik IJ. Neurology. 2000;54(5): 1080–1088.
26. Regeneration of primary sensory neurons. Donnerer J. Pharmacology. 2003;67(4):169–181.
27. Nerve growth factor and diabetic neuropathy. Pittenger G, Vinik A. Exp Diabesity Res. 2003;4(4):271–285.
28. Functional recovery enhancement following injury to rodent peroneal nerve by Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae). Wong KH, Naidu M, David RP, Abdulla MA, Abdullah N, Kuppusamy UR, Vikineswary S. Int J Med Mushrooms. 2009;11(3):225–230.
29. Potential activity of aqueous extract of culinary-medicinal Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) in accelerating wound healing in rats. Abdulla MA, Fard AA, Vikineswary S, Wong KH, Kuppusamy UR, Abdullah N, Ismail S. Int J Med Mushrooms. 2011;13(1):33–39.
30. Neuroregenerative potential of Lion’s Mane mushroom, Hericium erinaceus (Bull. Fr.) Pers. (Higher Basidiomycetes), in the treatment of peripheral nerve injury (Review). Wong KH, Naidu M, David RP, Bakar R, Vikineswary S. Int J Med Mushrooms. 2012;14(5):427–446.
31. Neurotrophic properties of the Lion’s Mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Lai PL, Naidu M, Vikineswary S, Wong KH, David RP, Kuppusamy UR, Abdullah N, Malek SNA. Int J Med Mushrooms. 2013;15(6):539–554.
32. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Nagano M, Shimizu K, Kondo R, Hayashi C, Sato D, Kitagawa K, Ohnuki K. Biomed Res. 2010;31(4):231–237.
33. Erinacine E as a kappa opioid receptor agonist and its new analogs from a basidiomycete, Hericium ramosum. Saito T, Aoki F, Hirai H, Inagaki T, Matsunaga Y, Sakakibara T, Sakemi S, Suzuki Y, Watanabe S, Suga O, Sujaku T, Smogowicz AA, Truesdell SJ, Wong JW, Nagahisa A, Kojima Y, Kojima N. J Antibiot. 1998;51(11):983–990.
34. Anti-MRSA compounds of Hericium erinaceus. Kawagishi H. Int J Med Mushrooms. 2005;7(3):350.
35. A double-blind study of effectiveness of Hericium erinaceus Pers. therapy on chronic atrophic gastritis. A preliminary report. Xu CP, Liu WW, Liu FX, Chen SS, Liao FQ, Xu Z, Jiang LG, Wang CA, Lu XH. Chin Med J (Engl). 1985;98(6):455–456.
36. Cytoprotective effects of Hericium erinaceus on gastricmucosa in rats. Yu CG, Xu ZM, Zhu QK, Zhang ZH, Chen ZR, Sun CH, Zhang YF, Wang N. Chin J Gastroenterol. 1999;4(2):93–96.
37. Effect of culinary-medicinal Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae), on Ethanol-induced gastric ulcers in rats. Abdulla MA, Noor S, Wong KH, Ali HM. Int J Med Mushrooms. 2008;10(4):325–330.
38. Gastroprotective effects of Lion’s Mane mushroom Hericium erinaceus (Bull.:Fr.) Pers (Aphyllophoromycetideae) extract against ethanol-induced ulcer in rats. Wong JY, Abdulla MA, Raman J, Phan CW, Kuppusamy UR, Golbabapour S, Vikineswary S. Evid Based Complement Alternat Med. 2013;2013:492976.
39. In vitro anti-Helicobacter pylori effects of medicinal mushroom extracts, with special emphasis on the Lion’s Mane mushroom, Hericium erinaceus (Higher Basidiomycetes). Shang X, Tan Q, Liu R, Yu K, Li P, Zhao GP. Int J Med Mushrooms. 2013;15(2):165–174.
40. Chinese Pharmacopoeia. Beijing : Chinese Medicine Science and Technology Publishing House, 2010.
41. Activity of aqueous extracts of Lion’s Mane mushroom Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) on the neural cell line NG108-15. Wong KH, Vikineswary S, Abdullah N, Naidu M, Keynes R. Int J Med Mushrooms. 2007;9(1):57–65.
42. Neurotropic and trophic action of Lion’s Mane mushroom Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) extracts on nerve cells in vitro. Moldavan MG, Grygansky AP, Kolotushkina OV, Kirchhoff B, Skibo GG, Pedarzani P. Int J Med Mushrooms. 2007;9(1):15–28.