Those interested in taking mushroom nutrition supplements are often faced with a bewildering variety of product forms produced through different growing and manufacturing processesWhereas 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