This strong inverse correlation between age / overall health and risk of developing severe symptoms from Covid-19 infection is the clearest indication we could have of the importance of supporting our immune health at this time.

While there is a lot we can do to support our immunity with good food, adequate exercise and sufficient sleep, supplements known to have a positive effect on our immune system also have a role to play, particularly if the immune system is already compromised by age or pre-existing health conditions.

When considering the different categories of immunologically active supplements, mushrooms have a particularly strong case for a place on our shelves at this time due to their well-documented ability to modulate our immune response, both increasing levels of immune activity where these are suppressed and decreasing levels of immune activation and cytokine production where these are elevated 1.

A number of epidemiological and clinical studies have confirmed the ability of mushrooms and mushroom-derived supplements to increase the effectiveness of both our innate and adaptive immune responses to a range of pathogens including viruses 2.

Polysaccharide extracts from different mushrooms, including Cordyceps (Ophiocordyceps sinensis / Cordyceps militaris), Coriolus (Trametes versicolor), Shiitake (Lentinula edodes) and Maitake (Grifola frondosa) have all been shown to exert an inhibitory effect on influenza virus in vivo.

Clinical studies have also shown benefit for extracts from: Zhu Ling (Polyporus umbellatus), Sun Agaric (Agaricus subrufescens), Reishi (Ganoderma lucidum) and Cordyceps in the treatment of Hepatitis B 3-6.

In patients with recurrent genital herpes supplementation with Coriolus extract resulted in increased immunity and fewer sick days and in clinical trials Coriolus, Reishi and combined mushroom polysaccharide extracts have all shown benefit in increasing clearance of high-risk HPV strains 7-9.

In addition enhanced protective immune response was seen from giving mushroom extracts alongside influenza vaccine in one in vivo study and FVe, a protein from Enokitake (Flammulina velutipes) was seen to significantly increase the anti-tumour protection given by vaccination against HPV-16 in another 10,11.

As well as supporting an effective immune response to viral infection several mushrooms contain compounds with direct anti-viral activity and two in particular stand out for their benefits in relation to the current pandemic.

Cordycepin (3’-deoxyadenosine) from Cordyceps species has been shown to inhibit viral replication in a number of studies 12. It also shows strong anti-inflammatory activity and has been shown to actively protect the lungs from acute injury due to the type of inflammatory immune response seen in more serious Covid-19 infections 13.

Triterpenes from Reishi also have strong anti-inflammatory activity and have been shown to inhibit viral replication and viral binding 14. Both triterpenes and proteins from Reishi have also been shown to inhibit angiotensin-converting enzyme activity, blocking conversion of ACE-1 to ACE-2 the form of the enzyme through which Covid-19 enters cells 15,16.

Both Cordyceps and Reishi are major components of MycoNutri IS Complex and Reishi-Cordyceps Complex making these particularly useful supplements at this time.
Of course, although mushrooms undoubtedly have an important role to play in supporting our immune system and helping protect us in case of infection, they are not a panacea.
In case of active infection, it would be appropriate to follow traditional treatment strategies for infectious diseases and shift the emphasis from ‘Supporting the Upright’ to ‘Clearing the Pathogen’ with anti-viral herbs.

References
He T, Zhao R, Lu Y, Li W, Hou X, Sun Y, Dong M, Chen L. Dual-Directional Immunomodulatory Effects of Corbrin Capsule on Autoimmune Thyroid Diseases. Evid Based Complement Alternat Med. 2016;2016:1360386. Epub 2016 Sep 18.
1. Powell M. Medicinal Mushrooms – A Clinical Guide 2nd Ed. Mycology Press. 2014.
2. Yan Sc et al. Clinical and experimental research on Polyporus umbellatus polysaccharide in the treatment of chronic viral hepatitis. Zhongguo Zhong Xi Yi Jie He Zazhi. 1988;8(3):141–143.
3. Liu J, McIntosh H, Lin H. Chinese medicinal herbs for chronic hepatitis B: a systematic review.Liver. 2001;21(4):280–286.
4. Gao YH, Zhou SF, Chen GL, Dai XH, Ye JX, Gao H. A phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) extract in patients with chronic Hepatitis В. Int J Med Mushrooms. 2002;4(4):321–328.
5. Hsu CH, Hwang KC, Chiang YH, Chou P. The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B. J Altern Complement Med. 2008;14(3):299–301.
6. Kono R, Nakajima A (Eds). Treatment of recurrent genital herpes with PSK. Kawana T. Proceedings of the International Symposium on Pharmacological and Clinical Approaches to Herpes Viruses and Virus Chemotherapy. Oiso, Japan, Sept. 10-13, 1984. Amsterdam : Excerpta Medica, 1985. pp. 271–272.
7. Donatini B. Control of oral human papillomavirus (HPV) by medicinal mushrooms, Trametes versicolor and Ganoderma lucidum: a preliminary clinical trial. Int J Med Mushrooms. 2014;16(5):497-8.
8. Couto JS, da Silva DP. Coriolus versicolor supplementation in HPV patients. [Poster]. 20th European Congress of Obstetrics and Gynaecology. March 7th, 2008.
9. Ichinohe T et al. Induction of cross-protective immunity against influenza A virus H5N1 by an intranasal vaccine with extracts of mushroom mycelia. J Med Virol. 2010 Jan;82(1):128-37.
10. Ding Y, Seow SV, Huang CH, Liew LM, Lim YC, Kuo IC, Chua KY. Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour-associated antigen enhanced antitumour immunity. Immunology. 2009;128(1Suppl):e881–894.
11. Qin P, Li XK, Yang H, Wang ZY, Lu DX. Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi. Molecules. 2019 Jun; 24(12): 2231.
12. Lei J, Wei Y, Song P, Li Y, Zhang T, Feng Q, Xu G. Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol. 2018 Jan 5;818:110-114.
13. Xia Q et al. A comprehensive review of the structure elucidation and biological activity of triterpenoids from Ganoderma spp. Molecules. 2014 Oct 30;19(11):17478-535.
14. Morigawa A, Kitabatake K, Fujimotot Y, Ikekawa N. Angiotensin Converting Enzyme-Inhibitory Triterpenes from Ganoderma lucidim. Chem. Pharm. Bull. 1986. 34;7:3025-3028.
15. Ansor NM, Abdullah N, Aminudin N. Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma lucidum (Curtis) P. Karst. BMC Complement Altern Med. 2013; 13: 256.

Whereas traditionally only the fruiting body, or in some cases the sclerotium (underground hyphal mass - ie. Polyporus umbellatus and Poria cocos) or conk (sterile fungal growth on the trunk of the tree - ie. Inonotus obliquus - Chaga), was harvested and either been consumed whole in food, as with Lentinula edodes (Shiitake) and Grifola frondosa (Maitake), or as teas made from aqueous decoctions of the fruiting body, as with Ganoderma lucidum (Reishi) and I. obliquus, nowadays many commercial mushroom products are produced from the mycelium of the mushroom grown either by liquid fermentation or as a mycelial biomass.

The following overview summarizes the features of the different dosage forms available.

Fruiting Body/Conk/Sclerotium

The traditional dosage form of medicinal mushrooms, the fruiting body, typically contains a higher level and number of different polysaccharides than the mycelium or culture broth with an increase in concentration with fruiting body growth until an optimum size is reached (approx. 17g for L. edodes and 180g for G. frondosa)6,7, 51.

In addition, concentrations of components such as triterpenes (G. lucidum) and other phenolic compounds (I. obliquus) tend to be higher in the fruiting body, where their bitter taste and natural anti-microbial properties act to discourage unwanted predators. Data from Antrodia camphorata suggests the level of triterpenes in the mycelium is 40% of that in the fruiting body and for many mycelial biomass products the relative discrepancy is likely to be greater owing to the presence of residual substrate in the mycelial biomass. For this reason G. lucidum mycelial biomass products tend to lack the characteristic bitter flavour of the triterpenes found largely in the fruiting body.

Extracts

For mushrooms where triterpenoid and other phenolic components are therapeutically important such as A. camphorata, G. lucidum and I. obliquus products derived from the fruiting body/conk are usual with, given their indigestible nature, extracts often used in agreement with traditional practice.

Extracts are also used to deliver high concentrations of polysaccharides or other active components. They are usually made from either the fruiting body or the mycelium through one of two main methods:

Aqueous (hot-water) extraction (traditional teas/decoctions) gives high polysaccharide concentrations but low levels of poorly water-soluble triterpenes. Crude polysaccharide extracts typically have around 30% polysaccharides with further purification possible.

Ethanolic (alcohol) extraction (traditional tinctures) delivers higher levels of triterpenes but fewer polysaccharides (ethanol precipitates the polysaccharides out of solution).

As well as offering higher concentrations of polysaccharides and other clinically important compounds, extracts may be preferred in cases of gut dysbiosis, from antibiotic use or otherwise, with resultant impaired ability to break down whole mushroom or mycelial biomass products (also in cases of colostomy).

For some mushrooms such as G. lucidum, aqueous extracts and ethanolic extracts can be combined to deliver high concentrations of both polysaccharides and triterpenes. Some practitioners such as Nanba have also reported good results from combining high concentration polysaccharide (beta-glucan) extracts with whole mushroom fruiting body52.

Spores and Spore Oil

The fruiting body exists to spread the spores of the mushroom and generates them in amazing quantities with a single fruiting body of Ganoderma applanatum (the artist’s conk) being estimated to produce up to 1 billion over its life at rates of up to 36,000 per second53.

While all mushrooms produce spores only the spores from Ganoderma lucidum have so far been investigated for their clinical potential with polysaccharides, triterpenes and sterols all contributing to their therapeutic activity54-57.

For increased bio-availability the hard outer shell of the spores (sporoderm) has to be ruptured using ultrasound or low temperature milling to produce shell-broken spore powder with a typical triterpene content of 2%. The oil can then extracted from the shell-broken spores to produce reishi spore oil, which can have a triterpene content of up to 30%.

Mycelium (liquid/submerged fermentation)

Liquid fermentation is the same technology used in the pharmaceutical industry to produce antibiotics and also to produce other industrial products such as fungal enzymes. The mushroom mycelium is cultured in a closed vessel with a liquid substrate containing all the essential nutrients for growth and growth parameters such as nutrient composition and temperature carefully controlled to optimise concentration of the desired components.

Because the substrate is a liquid the mycelium can easily be harvested and then either used as a therapeutic component itself or in most cases further processed to yield various extracts (eg. PSK). In addition, the extracellular metabolites secreted into the growth medium (broth) may also be harvested for their therapeutic properties (eg. Schizophyllan, an extracellular polysaccharide from Schizophyllum commune).

Mycelial Biomass

In mycelial biomass production the mushroom culture is inoculated into a sterile, grain-based substrate, often brown rice, and left to fully colonize the substrate. At the point at which it has exhausted the capacity of the substrate to support further growth and is about to produce fruiting bodies (primordia stage) the resultant mass of mycelium and residual substrate is dried and granulated to make a powder, which is then usually tabletted or encapsulated.

As well as mushroom mycelium and some residual grain, mycelial biomass products contain the full range of metabolites secreted into the substrate by the mycelium (especially antimicrobial compounds and exopolysaccharides), together with a wide variety of enzymes, including digestive enzymes (proteases, lipases etc.) and antioxidant enzymes (laccase, catalase and superoxide dismutase). They also contain substrate breakdown products such as arabinoxylans with therapeutic properties in their own right. Indeed, in supplements such as Biobran™, also known asMGN-3™(shiitake digested rice bran) and Avemar™ (yeast digested wheatgerm) the enzymatically transformed substrate itself is seen as the therapeutic entity and Stamets reports crude arabinoxylan content of mushroom mycelial biomass cultivated on short grain brown rice by his company, Fungi
Perfecti, as ranging from 7.8% in Agaricus subrufescens to 24% in Ophiocordceps sinensis.

While mushroom mycelial biomass products contain a wide range of bioactive molecules, levels of the key immunomodulating beta-glucans and related heteropolysaccharides are low. Stamets reports beta-glucan levels in the above form of mycelial biomass ranging from 1.23% in Hericium erinaceus to 2.96% in Inonotus obliquus with A. subrufescens 1.83%, Grifola frondosa 2.51% and Ganoderma lucidum 2.19%7.

Combination Products

There is some evidence that combinations of mushrooms can have a greater effect on the immune system of both humans and mice than single mushrooms and that blends of mushrooms extracts have greater cytotoxicity against cancer cells than single extracts in vitro58, 59.

Sawai et al report greater immunological activity with higher levels of macrophage activation and INF-y induction by a mixture of mushroom polysaccharide extracts than by the single extracts60. Stamets also reports a blend of seven mushrooms (mycelial biomass) as having enhanced NK cell activation in human spleen cells when compared to the individual mushrooms61.

Several commercial mushroom products are produced from multiple mushroom species including Active Hexose Correlated Compound (AHCC - an extract from the mycelia of several species of basidiomycete) that has shown efficacy in clinical trials62,63.

References

6. Higher Basidiomycota as a source of antitumour and immunostimulating polysaccharides (Review). Reshetnikov SV, Tan KK. Int J Med Mushr. 2001;3(4):361-394.
7. Potentiation of cell-mediated host defense using fruitbodies and mycelia of medicinal mushrooms. Stamets P. Int J Med Mushr. 2003;5:179-191.

51. Changes in immunomodulating activities and content of antitumour polysaccharides during the growth of two medicinal mushrooms, Lentinus edodes (Berk.) Sing, and Grifola frondosa (Dicks.: Fr.). Gray SF. Minato KI, Mizuno M, Kawakami S, Tatsuoka S, Denpo Y, Tokimoto K, Tsuchida H. Int J Med Mush. 2001;3(1):1-8.

52. Maitake extracts and their therapeutic potential - A review. Mayell M. Alt Med Rev, 2001;6(1).
53. Mushroom. Money NP. 2012 Oxford University Press, USA.
54. Antitumour activity of the sporoderm-broken germinating spores of Ganoderma lucidum. Liu X, Yuan JP, Chung CK, Chen XJ. Cancer Lett. 2002;182(2):155-61.
55. Sterols and triterpenoids from the spores of Ganoderma lucidum. Zhang CR, Yang SP, Yue JM. Nat Prod Res. 2008;22(13):1137-42.
56. Chemical constituents of the spores of Ganoderma lucidum. Zhang XQ, Pang GL, Cheng Y, Wang Y, Ye WC. Zhong Yao Cai. 2008;31(1):41-4.
57. Comparative studies on the immunomodulatory and antitumour activities of the different parts of fruiting body of Ganoderma lucidum and Ganoderma spores. Yue GG, Fung KP, Leung PC, Lau CB. Phytother Res. 2008;22(10):1282-91.
58. Cytotoxicity of Blended Versus Single Medicinal Mushroom Extracts on Human Cancer Cell Lines: Contribution of Polyphenol and Polysaccharide Content. Durgo K et al. Int J Med Mushr. 2013;15(5):435-448.
59. Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by the combination of Coriolus versicolor and Ganoderma lucidum. Hsieh TC, Wu JM. Int J Mol Med. 2013 Jul;32(1):251-7.

60. Extraction of conformationally stable (1-6)-branched (1-3)-glucans from premixed edible mushroom powders by cold-alkaline solution. Sawai, M., Adachi, Y., Kanai, M., Matsui, S. and Yadomae, T. Int J Med Mushr. 2002;4:3.
61. Potentiation of cell-mediated host defense using fruitbodies and mycelia of medicinal mushrooms. P.Stamets. Int J Med Mushr. 2003;5:179-191.
62. Immunomodulatory and anticancer effects of active hemicellulose compound (AHCC). Ghoneum M, Wimbley M, Salem F, McKlain A, Attalah N, Gill G. Int J Immunotherapy. 1995;1,1:23-28.
63. An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration. Ulbricht C et al. J Diet Suppl. 2013 Sep;10(3):264-308.v

Products that not becoming organic are:

• Antrodia (organic raw material not available)
• Mesima (correct species not available with organic certification)
• Red Yeast Rice Complex (organic Red Yeast Rice and Coenzyme Q10 not available)
• Reishi-Curcumin Complex (organic non-mushroom raw materials not available)

Due to the increased cost of the organic extracts (coupled with last year's fall in the value of sterling) there have had to be some price increases but these have been kept to the minimum possible in keeping with MycoNutri's dual commitment to quality and affordability (the powder prices have stayed the same but the quantity is now 200g) and in most cases will be more than offset by the increased efficacy of the new products.

The one product where a significant price increase is unavoidable is Reishi and because this is such an important mushroom MycoNutri have decided to continue offering a non-organic product alongside the new organic version.

There is also still a non-organic Cordyceps as the new organic Cordyceps militaris extract has a lower cordycepin concentration than the non-organic one.

There have also been changes to the formulations of three of the products:

• Lion’s Mane – Now includes a concentrated dual extract with high levels of diterpenes alongside the fruiting body and mycelial biomass to enhance the concentration of these key components.
• IS Complex – Vitamin C rich freeze-dried organic Acerola has replaced the non-organic food-state vitamin C and polyphenol-rich organic Matcha green tea has replaced the non-organic green tea extract.
• Reishi-Cordyceps Complex – Now includes Ashwagandha KSM-66 extract with 5% withanolides alongside the Corydyceps and Reishi dual-extract to further reinforce the Energy/Lung/Kidney/Adrenal/Immune/Mind supporting properties of this powderful combination.

Where there is an organic MycoNutri version available we have decided to discontinue the organic mycelial biomass products we have offered previously as these are not as strong as the MycoNutri versions and therefore less beneficial.

We are committed to supporting our customers with the best mushroom supplements available and welcome comments and suggestions which can be addressed to: info@mushroomnutrition.com

Here you will find all you favourite mushroom supplements in a more user-friendly, easy to navigate format, together with monographs from the second edition of Martin's book: Medicinal Mushrooms - A Clinical Guide.

If anything is not working the way you want please let us know and we will try to fix it as soon as possible.

Over the coming months we plan to expand the range of mushroom supplements we carry and also to post regular news updates so please sign-up via the link on the front page if you would like to be kept informed.