• Lee Carroll

Introducing... Lion's Mane!



In my last post I introduced an interesting medicinal fungus, Cordyceps. In a similar vein, today we will have a look at another visually distinctive fungal specimen with unique medicinal value: Lion’s Mane.


Lion’s Mane, Hericium erinaceus, is a fungus that feeds on the wood of certain dead/decaying trees (a saprotrophic fungus) [1]. There are many species in the Hericium genus, some still being discovered, from all over the world. They are all considered rare in nature but are an easily identifiable genus thanks to the striking white, beard-like formation of the fruiting body, and all members appear comparably useful [2]. Hericium spp. make for both a cherished edible (with a lobster-like texture, a delicate veal/chicken-like flavour, and a slightly fruity aroma reminiscent of coconut and lemongrass) as well as a powerful health ally.

With such a distinctive icicle-like morphology, there are many names commonly applied to this fungus, including bearded tooth, satyr’s beard, bearded hedgehog, bear’s head, and pom-pom mushroom. Hericium is itself Latin for hedgehog. The Chinese term is hóu tóu gū (monkey head mushroom), in Japan it is called yamabushitake (mountain priest mushroom), and in Korea it is known as norugongdengi-beoseot (deertail mushroom).



Traditionally the main application for medicinal use from East Asian traditions was for the treatment of chronic gastritis, gastric ulceration, and cancers of the oesophagus & stomach, as well as leukemia. Lion’s Mane was also valued for a variety of other ailments, including neurasthenia and general debility, as an antiseptic, immunostimulant, growth stimulant, and vulnerary. Interestingly, Lion’s Mane, when dissected, is visually reminiscent of a brain! Indeed, the current clinical focus is with neurological health.


Medicinal Application

Like all mushrooms, Lion’s Mane communicates beneficial and highly specific immunological messages due to its array of complex polysaccharides which are higher in the fruiting body than in the mycelium [3].


Lion’s Mane contains many other unique bioactive compounds that are still being elucidated. These come in primarily two categories: hericenones and erinacines. Hericenones are only produced in the fruiting body, (eleven hericenones (A-K) are identified thus far), and many of these enhance nerve growth factor (NGF) production. Erinacine A & B, both of which also promote NGF production, are also found in the fruiting body [4].

The mycelium does not contain hericenones but does contain many more biologically active erinacines (15 identified thus far, A-K, P-S), making for an unusually strong case to incorporate mycelial extracts alongside the fruiting body in this particular medicinal mushroom case [5, 4]. Currently we have evidence that the erinacines cross the blood-brain-barrier for direct interaction with the central nervous system, however other constituents are also suspected to have this capacity [6].



The neurotrophic and neuroprotective activity of Lion’s Mane puts it into a sharp focus as a potential treatment for neurological disorders, which is where much of the contemporary focus on Lion’s Mane is based. What do the clinical trials have to say??


In the early 2000s, a pilot study [10] of seven adults with mild dementia had promising results. The subjects ingested 5 g of fruiting body daily as part of the diet and after six months, all but one subject reported scores that indicated improved functional capacity (understanding, communication, memory, etc.), and all subjects experienced improved functional independence (capacity to eat, dress, walk, etc). Interestingly 3 bedridden patients were able to get up for meals after the administration. There was no placebo in this tiny study, but it set the scene for ongoing exploration. Since then two high-quality studies have looked at 3 g fruiting body daily for prevention/alleviation of cognitive impairment. Both found significant improvements in cognitive function of over 50-year-olds, one in a healthy population (3 months) [11], and the other in a mildly cognitively impaired population (4 months) [12]. In the latter, it only took two months for the improvements to reach statistical significance, and after ceasing Lion’s Mane intake, the cognitive function scores decreased again. We can infer from this that acute improvements to cognition are possible, however chronic use is required for long-term effects in this regard (just like beneficial effects of a healthy diet: regularity is the key)!


Just this year a high-quality pilot study [13] was published investigating an erinacine A-enriched extract from H. erinaceus mycelium in the treatment of patients with mild Alzheimer's Disease (AD). As mentioned, erinacine A is in the fruiting body, so the results here can best be applied to a combined mycelium and fruit body extract. This almost year-long intervention allowed the authors to conclude that Lion’s Mane exerts valuable protective neurocognitive benefits in patients with mild AD.


There is limited evidence yet, but one pilot study even indicates potential for symptoms of schizophrenia [14]. Ten subjects with refractory schizophrenia (disease unaffected by antipsychotic medication) took a standardised extract from Lion’s Mane fruiting body and demonstrated improved symptoms.


The same author reported a case study of an 86-year-old male with recurrent depressive disorder [15]. Treated with the same extract as in the schizophrenia study, he experienced remarkable neurocognitive improvements after six months. In the following year, a pilot study successfully alleviated the symptoms of depression and anxiety, and improved sleep quality in a cohort of otherwise healthy students [16]. Recently, 77 overweight/obese adults also verified these results [17], with a mixed mycelium and fruiting body extract, at 3.6 g daily for 2 months. The authors speculate that alterations in brain-derived neurotropic factor (BDNF)-signalling might play a role here. Low doses may well be adequate for the alleviation of depression, as 2 g of fruiting body daily in the diet was enough to elicit a significant reduction in scores for depression and indefinite complaints index (but not for sleep quality or menopausal indices) in a randomised double-blind placebo-controlled trial of thirty menopausal women [18]. It is possible that 2 g dose was not enough to affect sleep quality compared to the study that used 3.6 g and found success in this area, however sleep quality is affected by complex mechanisms and cohorts underlying health may indicate whether Lion’s Mane is effective for improving sleep or not (menopausal versus overweight condition). Actually, there is no evidence I am aware of that Lion’s Mane is useful for managing symptoms of menopause though this indication is often casually presented.


A study from the 1990s (of 250 subjects with diabetic polyneuropathy) found that dosing with recombinant human NGF for 6 months significantly improved nerve function [8]. While we do not have human studies of Lion’s Mane examining this effect yet, we do have plenty of experimental data indicative of promise in this regard. One fine example of this is a rat study that clearly demonstrates Lion’s Mane promotes peripheral nerve regeneration after nerve injury [9].



Beyond neuroprotective and anti-inflammatory activity, erinacine A and other cyathane diterpenes (related chemicals, many of which are present in Lion’s Mane), display significant antitumor effects in animal studies, apparently acting via direct modulation of the actin cytoskeleton. This is basically a filamentous structure inside cells with many complex roles vital to cellular function. Cancer cells can use actin to resist the cytotoxic responses of NK cells [21]. Erinacine A and friends perturb the actin cytoskeleton in tumour cells rendering them vulnerable to immune attack [22]. The various anticancer potentials of Lion’s Mane are beyond the scope of this brief overview, however it is worth reiterating that one of the primary traditional uses for Lion’s Mane was to treat stomach cancers along with other inflammatory conditions of the mucous membranes in the gastrointestinal tract. While we do not have scientific literature at human trial level to discuss this activity, it will undoubtedly be explored soon, as we have plenty of preclinical evidence to indicate worthiness of study. Not all this research is centred around the terpene components either, as the specific polysaccharides from Lion’s Mane also appear potent. For example, in vitro analysis of precancerous human gastric cells treated with Lion’s Mane polysaccharides finds they induce apoptosis [23].


NGF production complements this immunological activity, by supporting improved wound healing [24], which is no doubt relevant to its effectiveness in healing ulceration of the mucous membranes. This is not only in a gastroprotective context, but includes effectiveness in corneal ulceration, glaucoma and other ocular diseases, for example [7].

Preclinical research goes on to suggest an impressive capacity to regulate metabolic activity, with animal studies demonstrating improved body composition and fat/cholesterol metabolism in models of metabolic syndrome and obesity [25, 26]. There is so much more to say which is beyond the scope of this light introduction. I shall watch where the research leads on this unique medicinal fungus with great interest!


Safety, Quality and Dosing

While many in the genus appear to be valuable, the most significant body of work supports H. erinaceus so I recommend this species specifically for medicinal effect. Usually I do not encourage the use of mycelial extracts as the fruiting body (in most cases) is the only part of the fungus humans used traditionally. However, in the case of Lion’s Mane, research has demonstrated that there are active compounds (specific erinacines) in the mycelium that are not found in the fruiting body (and visa versa).



Studies show that 3-5 g per day is appropriate for the nervous system benefits as discussed. The Chinese Pharmacopoeia recommends 25-50 g daily [27], which is much larger than contemporary studies investigate, but I imagine this is relevant for that traditional gastric mucosa healing application. While this dose does not appear necessary for neurological effects, it is illustrative of how safe high intake is, and modern research supports this [28, 29].

I recommend Lion’s Mane particularly to those with any neurological degeneration and/or chronic neuroinflammation, including cognitive decline, depression, peripheral neuropathy, multiple sclerosis, etc. Also think of Lion’s Mane where there is poor mucous membrane integrity or ulceration. It is particularly valuable where impaired immunological signalling impacts on neurological, metabolic and gastric health.


If you would like a more in-depth and clinically-focussed take on this miraculous monkey-head of a mushroom, see my Lion’s Mane Monograph [COMING SOON!].


References

[1] Mori K, Obara Y, Hirota M, et al. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biol Pharm Bull. 2008 Sep;31(9):1727-32.

[2] Hallenberg, N., Nilsson, R. H., & Robledo, G. Species complexes in Hericium (Russulales, Agaricomycota) and a new species - Hericium rajchenbergii - from southern South America. Mycological Progress. 2012;12(2), 413–420.

[3] He X, Wang X, Fang J, et al. Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review. Int J Biol Macromol. 2017 Apr;97:228-237.

[4] Chong PS, Fung ML, Wong KH, et al. Therapeutic Potential of Hericium erinaceus for Depressive Disorder. Int J Mol Sci. 2019 Dec 25;21(1). pii: E163.

[5] Li IC, Lee LY, Tzeng TT, et al. Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines. Behav Neurol. 2018 May 21;2018:5802634.

[6] Limanaqi F, Biagioni F, Busceti CL, et al. Potential Antidepressant Effects of Scutellaria baicalensis, Hericium erinaceus and Rhodiola rosea. Antioxidants. 2020 Mar;9(234).

[7] Rocco ML, Soligo M, Manni L, Aloe L. Nerve Growth Factor: Early Studies and Recent Clinical Trials. Curr Neuropharmacol. 2018;16(10):1455-1465.

[8] Apfel SC, Kessler JA, Adornato BT, et al. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology. 1998 Sep;51(3):695-702.

[9] Wong KH, Kanagasabapathy G, Naidu M, et al. Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration. Chin J Integr Med. 2016 Oct;22(10):759-67.

[10] Kawagishi H, Zhuang C, Shnidman E. The anti-Dementia effect of Lion’s Mane mushroom and its clinical application. Townsend Letter for Doctors and Patients, 2004.

[11] Saitsu Y, Nishide A, Kikushima K, et al. Improvement of cognitive functions by oral intake of Hericium erinaceus. Biomed Res. 2019;40(4):125-131.

[12] Mori K, Inatomi S, Ouchi K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009 Mar;23(3):367-72.

[13] Li IC, Chang HH, Lin CH, 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 Jun 3;12:155.

[14] Inananga K, Matsuki T, Hoaki Y, et al. Improvement of refractory schizophrenia on using Amyloban®3399 extracted from Hericium erinaceum. Pers Med Universe. 2014;3:49–53.

[15] Inanaga, K. Marked improvement of neurocognitive impairment after treatment with compounds from Hericium erinaceum: A case study of recurrent depressive disorder. Pers Med Universe. 2014;3:46–48.

[16] Okamura H, Anno N, Tsuda A, et al. The effects of Hericium erinaceus (Amyloban® 3399) on sleep quality and subjective well-being among female undergraduate students: a pilot study. Personalized Medicine Universe. 2015 Jul 1;4:76-8.

[17] Vigna L, Morelli F, Agnelli GM, et al. Hericium erinaceus Improves Mood and Sleep Disorders in Patients Affected by Overweight or Obesity: Could Circulating Pro-BDNF and BDNF Be Potential Biomarkers? Evid Based Complement Alternat Med. 2019 Apr 18;2019:7861297.

[18] Nagano M, Shimizu K, Kondo R, et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res. 2010 Aug;31(4):231-7.

[19] Chiu CH, Chyau CC, Chen CC, et al. Erinacine A-Enriched Hericium Erinaceus Mycelium Produces Antidepressant-Like Effects Through Modulating BDNF/PI3K/Akt/GSK-3β Signaling in Mice. Int J Mol Sci. 2018 Jan 24;19(2):341.

[20] Lee KF, Tung SY, Teng CC, et al. Post-Treatment with Erinacine A, a Derived Diterpenoid of H. erinaceus, Attenuates Neurotoxicity in MPTP Model of Parkinson's Disease. Antioxidants (Basel). 2020 Feb 4;9(2):137.

[21] Al Absi A, Wurzer H, Guerin C, et al. Actin Cytoskeleton Remodeling Drives Breast Cancer Cell Escape from Natural Killer-Mediated Cytotoxicity. Cancer Res. 2018 Oct 1;78(19):5631-5643.

[22] Bailly C, Gao JM. Erinacine A and related cyathane diterpenoids: Molecular diversity and mechanisms underlying their neuroprotection and anticancer activities. Pharmacol Res. 2020 Sep;159:104953.

[23] Wang M, Zhang Y, Xiao X, et al. A Polysaccharide Isolated from Mycelia of the Lion's Mane Medicinal Mushroom Hericium erinaceus (Agaricomycetes) Induced Apoptosis in Precancerous Human Gastric Cells. Int J Med Mushrooms. 2017;19(12):1053-1060.

[24] Abdulla MA, Fard AA, Sabaratnam V, et al. Potential activity of aqueous extract of culinary-medicinal Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) in accelerating wound healing in rats. Int J Med Mushr. 2011 Jan;13(1):33-9.

[25] Hiraki E, Furuta S, Kuwahara R, et al. Anti-obesity activity of Yamabushitake (Hericium erinaceus) powder in ovariectomized mice, and its potentially active compounds. J Nat Med. 2017 Jul;71(3):482-491.

[26] Tsai YC, Lin YC2, Huang CC, et al. Hericium erinaceus Mycelium and Its Isolated Compound, Erinacine A, Ameliorate High-Fat High-Sucrose Diet-Induced Metabolic Dysfunction and Spatial Learning Deficits in Aging Mice. J Med Food. 2019 May;22(5):469-478.

[27] Chinese Pharmacopoeia, 2010. Beijing: Chinese Medicine Science and Technology Publishing House

[28] Li W, Zhou W, Lee DS, et al. Hericirine, a novel anti-inflammatory alkaloid from Hericium erinaceum. Tetrahedron letters. 2014 Jul 23;55(30):4086-90.

[29] Lee LY, Li IC, Chen WP, et al. Thirteen-Week Oral Toxicity Evaluation of Erinacine A-Enriched Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Mycelia in Sprague-Dawley Rats. Int J Med Mushrooms. 2019;21(4):401-411.

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