Chapter 101 Medicinal Mushrooms
Medicinal mushrooms have a very long history of use in Asia, Europe, and Russia, but have only become an important category of natural medicine in North America over the last decade or so. Worldwide, mushrooms are one of the fastest growing categories of medicinal supplements, with 1.2 million tons of medicinal mushrooms produced in 1981, 7 million tons in 1999, and 9.9 million tons in 2004. However, the U.S. market is only a small fraction of this volume.1 There have been several journals, books, and reviews written about mushrooms over the last decade in the United States.
Mushroom is not a taxonomic category, but a commonly used name. The definition of mushroom is: “a macrofungus with a distinctive fruiting body, which can be either hypogeous (below ground) or epigeous (above ground), large enough to be seen with the naked eye and to be picked by hand.”2 Taxonomically, mushrooms are mainly basidiomycetes with several species of ascomycetes. Mushrooms are neither plants nor animals, but are in a separate fungi kingdom. There are 14,000 to 22,000 known species of mushrooms, with an estimated 140,000 species worldwide. This shows that they are potentially a very large untapped resource, with an estimated 7000 species that have benefitted mankind.3 Even among the known species, there are a very small number of thoroughly investigated mushrooms. The fact that there is a large amount of documented ethnomedicinal uses and strong bioactivity of researched species gives us the impression that we should expect many more natural medicinal substances from mushrooms in the future.
There are several constituents of interest in medicinal mushrooms, with approximately 400 substances isolated from Ganoderma (Reishi) alone. The most studied constituents are polysaccharides, triterpenoids, nucleosides, ergosterol, fatty acids, protein/peptides, and trace elements. Of these, the most studied are various branched polysaccharides and triterpenoids. Most likely because of the large array of activity found from a variety of constituents, many health care practitioners consider medicinal mushrooms to be multiple medicinal supplements, akin to multiple vitamins and minerals.
Polysaccharides (in particular β-D-glucans) and polysaccharide protein complexes have immunomodulating effects on the body. Not new to the realms of natural healing, polysaccharides have been shown to stimulate nonspecific immune system function as well as exert antitumor activity through the stimulation of the host’s defense mechanism.4–6 These β-glucans have been termed “biological response modifiers,” due to the large array of functions attributed to them. Although the mechanisms behind the various polysaccharides have been only partially worked out, there are many theories with no complete consensus.
Both clinical and animal studies have shown that the β-glucans can activate certain aspects of the immune system. The β-glucans found in medicinal mushrooms have the ability to stimulate macrophages,7 natural killer cells,8 T cells,9 and the production of immune system cytokines. Mushroom polysaccharides may also be able to increase dendritic cell function.10 There is evidence that β-glucans function by binding to membrane complement receptor type 3 (CR3, α-Mβ2 integrin, or CD11b/CD18) on immune effector cells. The intercellular events that occur after glucan-receptor binds have not been fully worked out. The shape, size, degree of branching, and association with protein or peptide groups significantly affect the biological activity observed.
Much of the theoretical research is done in vitro, with no clear understanding of how these extremely large molecules are absorbed into the bloodstream and arrive at the receptor sites. The concept of pinocytosis, or “cell drinking” has been suggested as a mechanism of absorption that leaves whole or partial molecules intact.
Some subscribe to an alternative theory of signals being generated by the various polysaccharides and protein complexes from their location in the intestinal tract. It is thought that these signals are what really activate the receptor sites in the immune system.
Triterpenoids contain a lanostane skeleton often with steroidal-like shapes. The smaller molecular weights have shown biological activity, such as antitumor, immunomodulating, hepatoprotective, antiviral, and antioxidant effects.11 There are many varieties of triterpenoids, with Reishi having over 120 alone.12,13
Mushrooms are the only nonanimal source of vitamin D. When exposed to ultra violet light, mushrooms were shown to convert ergosterol into vitamin D2. The amount of vitamin D found in these mushrooms is high enough to support vegans through the winter months. High vitamin D2 mushrooms are now available in United States, but shelf life studies and more research are still needed in this area.14–16
Many of the medicinal mushrooms contain antioxidants such as ascorbic acid, carotenoids, ergothioneine, phenolic compound, superoxide dismutases, and tocopherols.17 Medicinal mushrooms with antioxidant effects include: Agaricus blazei,18 Chaga19–21 Flammulina velutipes,22 Maitake,23 Reishi,24,25 and Shiitake.26,27
Because of the natural environment of most mushrooms, it is not surprising that they have strong activity against bacteria and fungi. It is interesting that only compounds from microscopic fungi have been marketed as antibiotics, when there is a large array of compounds from most medicinal mushrooms. Several constituents have shown broad-spectrum activity. Some, including sesquiterpenoid hydroquinones from Ganoderma sp. have shown activity against multiresistant bacterial strains such as methicillin-resistant Staphylococcus aureus28–30 Oxalic acid as found in Shiitake, as well as ethanolic mycelial extract, have shown antimicrobial action.31,32 A review summary of Aphyllophorales is provided by Zjawiony.33
In contrast to bacterial and fungal infection, allopathic medicine has little for viral infections. There is great promise from both whole extracts of mushrooms, as well as from isolated compounds. This can be observed with direct contact of the viruses and indirect antiviral effect resulting from immunologic activity of the polysaccharides and other compounds.34 Several triterpenes of Reishi and water extract of Chaga have activity against HIV-1.35,36 Extract of Chaga also shows antiviral action against influenza A and B.37 Ergosterol found in several mushrooms also has an antiviral action.38 Many other mushrooms, including water extract Shiitake mycelium and protein-bound polysaccharides (polysaccharide-K [PSK] and polysaccharide-peptide [PSP]) from Coriolus and D-fraction from Maitake, show multiple antiviral function.39–44
Some mushrooms have long folklore associated with their use on cancer, including Chaga, which was used in the sixteenth and seventeenth century in Eastern Europe to treat cancer,45 and Reishi (Ling Zhi), which was used in China over 2000 years ago. Several extracts of whole mushrooms, as well as isolated compounds including triterpenes, ergosterol, and polysaccharides, have shown well-documented antitumor action. Most of the medicinal mushrooms reviewed here have shown various actions in this area.
Although several of the mushrooms can stimulate the immune system, some can suppress immune function. Interestingly, sometimes both stimulatory and inhibitory functions can be found in the same mushroom. Reishi was shown to inhibit histamine release.46,47 Isolates of Chaga, including ergosterol, hispolon, and hispidin, have been found in many mushrooms to have antiallergic action.48,49,49a
Several mushrooms have strong action of regulating cholesterol. Reishi50,51 and Agaricus blazei52,53 were shown to decrease cholesterol levels. Shiitake mushroom contains an anticholesterol compound called eritadenine.54 Oyster mushroom has a naturally occurring statin drug known as lovastatin (brand name: Mevacor, Altoprev).55 Many studies have shown that consumption of several of these mushrooms can control cholesterol.30,56
With the increase of both type 1 and type 2 diabetes around the world, more effective treatments are needed. Several medicinal mushrooms can lower elevated blood sugars. Polysaccharide from Maitake,57–59 Ganoderan A and B from Reishi,59–62 glucan-protein complex from Coriolus,63 as well as whole extract and constituents from Chaga,64 A. blazei,65–67 and Cordyceps68–70 all have blood sugar regulating effects. The mechanism has not been worked out for most mushrooms, but Maitake action was shown to be an α-glucosidase inhibitor.71
Several ganoderic acids from Reishi have been shown to have stronger antiinflammatory action than acetylsalicylic acid.72 The ergosterol found in many mushrooms was shown to inhibit cyclooxygenase 1 and 2 activity.23
Ganoderic acids, some glucans, and other compounds from Reishi showed liver protection both in vitro and vivo.73–75 Reishi was also shown to have activity against hepatitis B.76 Other mushrooms, especially Coriolus, showed strong protective action for the liver.
Used as a medicine in China for over two thousand years, Reishi is described in the Shen Nong’s Classic and Pen T’sao Kang Mu. Reishi was so important for the upper class of China that it was a major symbol of health and longevity for the Emperor in the Forbidden City. Having hundreds of β-glucans and triterpenes, Reishi has a wide range of uses. Research showed that it can be used therapeutically for cancer,85,86 immune system issues,87,88 cardiovascular system and respiratory problems, as well as urinary tract symptoms. It is antibacterial,89 antiviral,90,91 antifungal,92 an angiotensin-converting enzyme inhibitor,93 inhibits blood platelet aggregation, is protective to the liver,94,95 and protects the body from radiation.96 Reishi lowers blood cholesterol and other blood lipids,51 reduces allergies and asthma, while reducing autoimmune issues. It is antioxidant, hypoglycemic, antifibrotic, and increases the body’s vitality. Reishi calms the mind, reduces circular arguments, and aids in insomnia.
Cordyceps is a parasitic fungus that grows out of insects. It has a long history of use in China and Tibet, but has also been used by indigenous peoples around the world.97 Cordyceps is specific for the respiratory tract, working as a bronchial dilator. Heavily used by athletes, Cordyceps aids in both getting more oxygen into the cells and increasing endurance.98 Cordyceps is used mostly for relief from bronchial inflammation and as an expectorant. It is well known to relieve exhaustion, night sweats, sexual impotency, and acts as a sedative. It benefits the kidneys, lungs, and gonadal function. It is specific for uterine fibroids. Cordyceps will stimulate immune function (due to CS-1) by activating T cells and B cells, while increasing interleukin-1 (but not 2) and γ-interferon. It has also been shown to increase erythroid progenitor cells and erythroid colony forming units in bone marrow. Sedative and even hypnotic activity can be attributed to the amino acid content. Reduction of cholesterol and plasma triglycerides has been observed, as well as increased spermatogenesis. Improvement in arrhythmia, in chronic kidney problems, liver function after hepatitis B, and good success with treating tinnitus, have all been observed.99 It has been used against cancer,100,101 as an antidepressant,102 to promote cellular health,103,104 to regulate blood lipids,105–107 for the inhibition of infection and reverse transcriptase activity of HIV,108,108a to increase both male and female fertility, and as an aphrodisiac.109
This mushroom and its isolates are some of the most studied of all medicinal mushrooms. In particular, the glucan-protein complex of PSK (Kresin, PSP) is used in cancer therapy to counteract the immune depressing action of common chemotherapy. Approved in 1980 by the Japanese equivalent to the U.S. Food and Drug Administration for concurrent use with chemotherapy, it is covered by all health care plans in Japan.110 Both the isolate and the mushroom were shown to increase survival time of cancer patients.111 In large studies, it was also shown to be useful in stomach cancer, colorectal cancer,112 small cell carcinoma,111 and non-small cell lung carcinoma.113 PSK was shown to enhance activity of the chemotherapeutic drugs doxorubicin and etoposide.114,115 U.S. cancer doctors have acknowledged that both PSK and whole mushroom extract show promise for chemoprevention due to multiple effects on the malignant process and reducing side effects of oral dosage.116 These studies, published in Lancet, found the results to be significant.117–119 The sales for these unique all-natural compounds have reached several hundred million dollars a year in Japan and China, making them the most widely used products in those countries by people facing serious immune challenges.120