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Mushrooms - The Fungal Pharmacy

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<strong>Mushrooms</strong>:<br />

Our <strong>Fungal</strong> <strong>Pharmacy</strong><br />

Sara Thyr, ND


Fungi Characteristics<br />

• 100,000 described species<br />

• Mycologists estimate may be more than 1.5<br />

million species<br />

• Classified in kingdom Fungi (eukaryotic)<br />

• Can grow to enormous size – 1500 acres


• Are decomposers<br />

Fungi<br />

• Absorb nutrients from their environment<br />

• Break down organic matter from dead<br />

organisms, leaves, garbage and other waste<br />

• When break down organic compounds, are<br />

released into environment where are recycled


Form vital symbiotic relationships<br />

• Most terrestrial plants have fungal partners<br />

• Live in close association with roots<br />

• Help plants obtain phosphate ions and other<br />

minerals from the soil<br />

• Lichens are symbiotic relationship of fungi<br />

and algae or cyanobacteria


How fungi get nutrients<br />

• Like animals, fungi are heterotrophs<br />

• Absorb food from environment (preformed<br />

carbon molecules)<br />

• Infiltrate a food source and secrete digestive<br />

enzymes onto it<br />

• Rapidly converts nutrients into new cell material


Structure - chitin<br />

• Cell walls contain chitin (a complex<br />

carbohydrate)<br />

• Chitin is also component of external skeletons<br />

of insects and other arthropods<br />

• Chitin is resistant to breakdown by most<br />

microorganisms


Structure


Structure<br />

• Fungi contain network of filaments<br />

• Multicellular body contains long, branched threadlike<br />

filaments called hyphae<br />

• As hyphae grow, a tangled mass or network called<br />

mycelium is formed<br />

• Spores (for those w sexual reproduction) produced on<br />

fruiting structures (sporangia - familiar part of mushroom<br />

is fruiting body)


Life cycle of fungi


Controversy in classification<br />

• Fungi are more closely related to animals than plants!<br />

• Like plants: have cell walls & vacuoles, are sessile; many inhabit the soil<br />

• Unlike plants: fungal cell walls do not contain cellulose (rather contain<br />

chitin – as in insect skeletons)<br />

• <strong>Fungal</strong> mode of nutrition differs from plants – cannot produce their own<br />

organic materials<br />

• Like animals, fungi are heterotrophs<br />

• Like animals, fungi have plate-like cristae in their mitochondria<br />

• Based on structural characters and molecular data, systematists now<br />

view fungi as more closely related to animals than to plants


5 Main <strong>Fungal</strong> Phyla


Glomeromycetes are symbionts<br />

with plant roots<br />

• Form intracellular association with roots of<br />

most trees and herbaceous plants<br />

• Assn. between hyphae of fungi and roots of<br />

plants are called mycorrhizae<br />

• Mutualistic symbiotic association – both<br />

benefit


• 32,000 species<br />

• Great impact on humans<br />

Ascomycetes<br />

• Make cheeses, bake bread, and eat (morels and truffles)<br />

• Produce antibiotics<br />

• Form mycorrhizae with tree roots<br />

• 40% join with algae or cyanobacteria to form lichens<br />

• Negative side: cause most fungal diseases of plants and<br />

animals


• Over 30,000 species<br />

Basidiomycetes<br />

• Largest and most familiar of the fungi<br />

• Many are decomposers that obtain nutrients by breaking<br />

down organic matter<br />

• Mushroom is formed as fruiting body – more formally –<br />

basidiocarp<br />

• Lower surface of the cap consists of many gills where<br />

basidiospores form


Reproduction


Ecological importance<br />

• Free-living decomposers – absorbing nutrients from organic wastes and<br />

dead organisms<br />

• Degrade cellulose and lignin, the main components of plant cell walls<br />

• Release water, CO2, and minerals – which are recycled<br />

• Without this continuous decomposition, essential nutrients would remain<br />

locked up in huge mounds of animal carcass, feces, branches, logs and<br />

leaves<br />

• <strong>The</strong> nutrients within them would not be unavailable for use by new<br />

generations of organisms<br />

• Life would eventually cease!!!


Symbiosis<br />

• Important symbiotic relationships w/ animals, plants,<br />

bacteria<br />

• 3-way symbiotic relationship w a fungus, a grass and a<br />

virus has recently been reported<br />

• In geothermal hot spots of Yellowstone<br />

• When has specific virus, fungus is heat tolerant and confers<br />

this to the grass (when virus not present, no heat<br />

tolerance)


Get along well w/ others<br />

• More than 200 species of ants farm fungi<br />

• 80% of plants have mycorrhizae<br />

• Many cannot grow well without their fungal partners<br />

• Improve soil by decreasing water loss and erosion<br />

• Can reclaim soils damaged by pollution<br />

• Mycorrhizae can modify toxic heavy metals, such as<br />

cadmium, so that plants cannot absorb them


Bioremediation<br />

• Some fungi can biodegrade pesticides,<br />

herbicides<br />

• Some break down coal tars and petroleum<br />

• Convert into CO2 and their basic elements<br />

• Fungi and bacteria can decontaminate farm<br />

land and clean up oil spills


Fuel Impact<br />

• Renewable fuel companies are researching fungi for fuel<br />

production<br />

• Recently a fungus was discovered than synthesizes 55<br />

hydrocarbons, perhaps to inhibit growth of other<br />

organisms<br />

• Researchers may be able to use the genes of this fungus to<br />

engineer other microorganisms to efficiently produce fuel


Fungi in Medicine<br />

• 1928 – Alexander Fleming discovered penicillin<br />

produced by the mold Penicillium notatum<br />

• Other Rx from fungi: cephalosporin ABx, statins,<br />

and cyclosporine<br />

• Claviceps purpurea infects rye and produces ergot<br />

– used to induce labor, stop uterine bleeding,<br />

treat HTN, and some migraines.


Penicillium conidiophores


Yummy!<br />

• Yeasts produce ethyl alcohol and carbon dioxide from<br />

sugars – beer and bread!!!<br />

• Roughly 200 species are edible (roughly 30 are found in<br />

supermarkets)<br />

• Cheeses such as Roquefort, Brie and Camembert not<br />

possible without species of Penicillium (the blue spots are<br />

masses of conidia)<br />

• But – watch out for the 70 poisonous species


Death cap (Amanita phalloides)


Medicinal <strong>Mushrooms</strong><br />

• Have been used in Chinese medicine for<br />

thousands of years<br />

• Western researchers are starting to catch on<br />

• Myriad mushrooms to discuss


Properties<br />

• Plant cell walls made of cellulose, beta 1-4<br />

linked glucose molecules<br />

• Fungi cell walls made of chitin, beta 1-3<br />

linked polysaccharide chain (1-3 , 1-6 b-<br />

glucan


<strong>Fungal</strong> beta glucan


Beta glucans<br />

• Yeast and oats also form beta glucans<br />

• Structure of mushroom beta glucans is more diverse<br />

• <strong>The</strong>refore have higher levels activity in immune system<br />

• Mushroom polysaccharides have immunological activity<br />

– 77.5% from mushroom fruiting body<br />

– 20.8% from mycelium<br />

– 2.0% from culture filtrate (broth)


• Proteins<br />

• Tripterpenes<br />

• Sterols<br />

• Chitin<br />

• Enzymes<br />

Active properties<br />

• Polysaccharides!! Most widespread


Proteins<br />

• Ling Zhi-8 (LZ-8) from Ganoderma lucidum (Reishi)<br />

• Fve, EA-6 and Flammulin from Flammulina velutipes (Enokitake)<br />

• Immune modulation – act on monocytes; effect T-cell activation<br />

• Ribosome inactivation<br />

• Anti-HIV – Velutin inhibits HIV reverse transcriptase<br />

• Anti-fungal<br />

• Nuclease activity<br />

• Lectins have been isolated from many mushrooms, including F.<br />

velutipes, Grifola frondosa and G. lucidum.


Triterpenes<br />

• Families of ganoderic and lucidenic acids from Ganoderma lucidum<br />

are best known, give it many therapeutic properties<br />

• Including: anti-cancer, anti-inflammatory, anti-histamine,<br />

hypotensive and sedative actions<br />

• Betulinic acid from Birch trees, taken up by Inonotus obliquus<br />

(Chaga) – anti-cancer, anti-inflammatory, and anti-viral<br />

• Antrodia camphorata – unique Taiwanese mushroom – high levels<br />

of triterpenes


Sterols<br />

• Principal sterol is ergosterol, with H. erinaceus<br />

fruiting body containing high amounts<br />

• Anti-tumor activity has been shown, as well as<br />

anti-angiogenic properties<br />

Isolation of an antitumour compound (Ergosterol) from Agaracus blazei Murill and its mechanism of action. Takaku T, Kimura Y, Okuda H. J Nutr.<br />

2001;131:1409-1413<br />

• Anti-aging activity on par with resveratrol<br />

Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene Weng Y,<br />

Xiang L, Matsuura A, Zhang Y, Huang Q, Qi J. Biorreg Med Chem. 2010;18(3):684-1002


Chitin<br />

• Primary component of fungal cell walls<br />

• Effects on innate and adaptive immune responses<br />

• Ability to recruit and activate innate immune cells<br />

• Can induce cytokine and chemokine production<br />

• Anti-bacterial and antioxidant activity<br />

• However is component of allergy-triggering allergens<br />

– including those in shrimp, crab and house dust mite


Enzymes<br />

• Digestive enzymes (proteases, lipases, etc.)<br />

• Antioxidant enzymes (laccase, catalase,<br />

superoxide dismutase [SOD])<br />

• SOD is acid-labile - no bioactivity<br />

• Tyrosinase – genoprotective effect in vitro


Polysaccharides – Key to Immune<br />

activity<br />

• Most widespread and most immunologically important<br />

• Profound impact on immune system<br />

• Mediated by a number of fungal polysaccharide-specific<br />

receptors on surface of several immune cell types<br />

• Key immune cells are hard-wired to respond to the<br />

presence of fungal polysaccharides<br />

• Immune system most likely evolved under constant<br />

challenge of fungal pathogens


Immune system activation by fungal beta glucans


<strong>Fungal</strong> Polysaccharides Effect on<br />

• Increase antibody production<br />

Immune System<br />

• Increase lymphocyte activating factor (IL-1) production<br />

• Increase tumor necrosis factor production<br />

• Increase colony stimulating factor production<br />

• Increase complement C3 production<br />

• Increase IFN-gamma production<br />

• Increase IL-2 production<br />

• Reduction in the level of IL-2 needed to produce a cytotoxic response<br />

• Th1 activation


Immune response (cont.)<br />

• Macrophage activation<br />

• Neutrophil activation<br />

• Cytotoxic T-cell activation<br />

• Lymphokine activated killer cell proliferation<br />

• Enhanced maturation and tumor infiltration of dendritic cells<br />

• Th2 suppression<br />

• Reduce IL-4 production<br />

• Inhibit prostaglandin synthesis<br />

• Inhibit delayed type hypersensitivity<br />

Powell, Martin. Medicinal <strong>Mushrooms</strong>: A Clinical Guide. Mycology Press. 2010.


Shift for Chronic Health Dso.<br />

• Mushroom polysaccharides promote shift in pattern of<br />

immune response<br />

• Cancer, auto-immune disorders, allergic health conditions<br />

• Shift from pro-inflammatory, Th2 dominant to cytotoxic,<br />

Th1 dominant<br />

• Increases especially critical are in Th1 cytokines such as IL-<br />

2, IFN-y<br />

• Decrease in Th2 cytokines such as IL-4


Extraction Process<br />

• Hundreds of mushroom products on shelves<br />

• Most research done on hot water extracts<br />

• Or hot water extracts w/ alcohol extract<br />

• Know what the process is for extraction<br />

• Human GI tract cannot break down chitin


Fruiting body or Conk<br />

• Fruiting body has highest level of different polysaccharides v<br />

mycelium or culture broth<br />

• Conk – sterile fungal growth on tree trunk (Inonotus obliquus)<br />

• Triterpenes in G. lucidum higher in fruiting body<br />

• Antrodia camphorata data show triterpenes in biomass 40% of that<br />

in fruiting body<br />

• Biomass products tend to have leftover substrate, not just<br />

mycelium


Extracts<br />

• Aqueous extracts (traditional teas/decoctions) give high<br />

polysaccharide concentrations but lower levels of triterpenes<br />

• Ethanol (alcohol) extracts yield more triterpenes but fewer<br />

polysaccharides<br />

• Some companies do both processes and combine in products<br />

• Extracts preferred in cases of gut dysbiosis or impaired ability<br />

to break down whole mushroom or biomass products


Spores<br />

• Fruiting body exists to spread spores in<br />

reproduction<br />

• Rich in fatty acids, which have some<br />

therapeutic action<br />

• G. lucidum spores v fruiting body show little<br />

difference in immunological activity


Mycelium (liquid/submerged<br />

fermentation)<br />

• Liquid fermentation is used in pharm industry to produce<br />

antibiotics (also fungal enzymes)<br />

• Controlled situation for nutrients and temperature to get<br />

most of desired components<br />

• Mycelium easily harvested from liquid and processed into<br />

extracts (PSK & Lentinan)<br />

• Metabolites secreted into broth may also be harvested<br />

(Schizophyllan – from Schizophyllum commune)


Mycelial Biomass (solid state<br />

fermentation)<br />

• Mushroom culture is inoculated into sterile, grain-based substrate<br />

(brown rice)<br />

• Once substrate is exhausted and about to produce fruiting bodies,<br />

mass of mycelium and residual substrate is dried and granulated<br />

• Extract contains antibiotics, exopolysaccharides, enzymes,<br />

antioxidants (catalase, SOD) and substrate breakdown products<br />

arabinoxylans (have own therapeutic value)<br />

• Examples are Biobran, MGN-3 (shitake digested rice bran) and<br />

Avemar (yeast digested wheat germ)<br />

• Have range of bioactive molecules, but key immunomodulating<br />

beta-glucans and related polysaccharides are low


Side Effects/CI<br />

• Large-scale studies show minimal side effects<br />

• None serious (rash, redness, nausea)<br />

• Bowel changes in a few patients, resolves in 2-3 days<br />

• Avoid in patient w/ mushroom allergy<br />

• Avoid in patients on Coumadin or heparin (some have<br />

blood thinning properties)<br />

• Avoid in patients with Hx organ transplant


Ideal Medicinal <strong>Mushrooms</strong><br />

• Agaricus brasiliensis/Agaricus blazei<br />

• Armillaria mellea<br />

• Auricularia auricula<br />

• Cordyceps sinensis<br />

• Ganoderma lucidum (Reishi)<br />

• Grifola frondosa (Maitake)


Medicinal <strong>Mushrooms</strong><br />

• Hericium erinaceus (Lion’s Mane)<br />

• Inonotus obliquus (Chaga)<br />

• Pleurotus ostreatus (Oyster mushroom)<br />

• Trametes versicolor/Coriolus versiclor (Turkey<br />

Tail)


G. lucidum


Ganoderma lucidum (Reishi)<br />

• Swiss Army Knife of mushrooms<br />

• Hx use over 2000 years<br />

• “Ten-thousand-year mushroom”<br />

• “Mushroom of immortality”<br />

• “Herb of Spiritual Potency”<br />

• Traditional use by Taoist monks to promote centered calmness,<br />

improve meditative practices and attain a long and healthy life<br />

• Revered in Japanese culture – considered the most important of all<br />

medicinal mushrooms


G. lucidum<br />

• Polysaccharides and triterpenes provide medicinal action<br />

• Chitin contributes to hardness of Reishi<br />

• Must do decoction to extract medicinal benefits<br />

• Boil 2-15 g of chopped or powdered Reishi mushroom in 2L<br />

water, until 2/3 of water is reduced<br />

• Macerate 90 g chopped or powdered Reishi in 500 ml rice wine<br />

for 10 days<br />

American Herbal Pharmacopoeia & <strong>The</strong>rapeutic Compentdium. Reishi Mushroom. Ganoderma lucidum. Standards of<br />

Analysis, Quality Control, and <strong>The</strong>rapeutics. Ed: Roy Upton. April 2006


G. lucidum<br />

• Very high polysaccharide and triterpene –<br />

over 130 compounds have been isolated in<br />

families of ganoderic and lucidenic acids<br />

• Fruiting bodies contain 41% beta glucan<br />

• Is an adaptogen


Health Benefits seen from ganoderic and<br />

lucidenic acids:<br />

• Inhibit histamine release<br />

• Inhibit viral induction<br />

• Hepatoprotective<br />

• Antioxidant<br />

• Anti-hypertensive (ACE inhibiting)<br />

G. lucidum<br />

• Anti-tumor<br />

• Inhibit cholesterol synthesis<br />

• CNS sedation<br />

• Anti-inflammatory<br />

• Anti-microbial<br />

• Induce apoptosis<br />

• Immune modulation


G. lucidum in Cancer<br />

• Long Hx traditional Tx of cancer, credited w many cases of<br />

spontaneous remission<br />

• Triterpenes cytotoxic to many cancer cell lines<br />

• Inhibit nuclear transcription factor NF-kappaB<br />

• This particularly important v breast and prostate CA as<br />

important in hormone independent growth<br />

• Increase NK cell activity and Th1 cytokine and decrease<br />

TH2 cytokine levels in advanced lung cancer patients


G. lucidum in athletes<br />

• Hot water extracts have been shown to have<br />

anti-inflammatory effects equal to 5 mg<br />

hydrocortisone (220 mg Reishi extract)


G. lucidum in allergies<br />

• Suppression of tumor necrosis factor-alpha<br />

confers strong anti-inflammatory effects<br />

• Also suppression of IL-6, NO and PGE2 via NF-<br />

KB signaling pathway<br />

• Component in Chinese formula shown to<br />

completely block anaphylactic reactions in<br />

mouse model of peanut allergy


Reishi and Liver Dz.<br />

• Tx hepatitis – triterpene component<br />

• Prevent hepatic fibrosis via inhibiting<br />

proliferation of hepatic stellate cells


Cardiovascular benefits<br />

Polysaccharides and triterpenes are:<br />

• Hypolipidemic<br />

• Hypotensive<br />

• Anti-thrombotic<br />

• Decrease chest pain and improve ECG<br />

• Decrease SOB and cardiac palpitation<br />

• Mild ACE inhibitory activity<br />

A phase I/II study of ling zhi mushroom Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetidae) extract in patients with coronary heart disease.<br />

Gao Y, Chen G. Dai X, Ye J, Zhou S. Int J Med Mushr. 2004;6(4):30


Other health conditions<br />

• Insomnia/anxiety – spirit mushroom, mental stabilization<br />

• Rheumatoid arthritis – immune modulatory and anti-<br />

inflammatory; dec RA synovial fibroblasts (in vitro) (NFKappaB pathway)<br />

• Anti-aging – traditionally to promote longevity, shown to inhibit beta-<br />

amyloid synaptic toxicity (Alzheimer’s), broad spectrum cardiovascular,<br />

neurological and immune benefits<br />

• Blood sugar control – elevates plasma insulin, enhances tissue<br />

utilization of glucose, enhance liver metabolism of glucose


G. lucidum dose and CI<br />

• Folk use in CA: 25-300g/day fruiting body decoction<br />

• Avg. concentration of 15:1 gives 2-20g/day of extract<br />

(most practitioners use 3-6 g/day)<br />

• For other conditions 1-3 g/day are common<br />

• Triterpenes are alcohol soluble but ideal to do HWE 1st<br />

• Caution on anti-hypertensive and sedative meds; on<br />

anti-coagulant drugs


Agaricus brasiliensis/Agaricus blazei Murrill


Agaricus brasiliensis (Sun Agaric)


A. brasiliensis in Cancer<br />

• Quickly becoming very popular medicinal mushroom<br />

• Polysaccharide extracts have strong activity against lung and ovarian<br />

cancer, Ehrlich ascites cancer and sarcoma<br />

• Synergistic benefits with chemo- and radiotherapy<br />

• Decreased cachexia and promoted weight gain while reducing tumor size<br />

(rat cachexia model)<br />

• Reduced chemotherapy related side effects in human volunteers (2008<br />

study) including appetite loss, alopecia, emotional stability and general<br />

weakness<br />

• Most research is positive, a few studies have shown no effect


A. brasiliensis/Agaricus blazei Murrill<br />

• Anti-infective and Anti-tumor properties<br />

• Prevents side effects of chemo and radiation<br />

• Type of extract important in immune system effect<br />

• liquid mushroom drink (AbM, H. erinaceus, G. frondosa)<br />

Effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer G. Hetland, E. Johnson, T.<br />

Lyberg, S. Bernardshaw, A. M. A. Tryggestad & B. Grinde Scand J Immunol. 2008 Oct;68(4):363-70. doi: 10.1111/j.1365-<br />

3083.2008.02156.x


A. brasiliensis & other conditions<br />

• Diabetes – decreases cholesterol and glucose levels<br />

• Allergies – reduces Th2 mediated allergic rxn (AndoSan)<br />

• Hepatoprotective – Tx hep B, reduced liver enzymes (20g<br />

bid x 3 months)<br />

• Fruiting body extract are in most studies<br />

• Usual dose 3 g/day polysaccharide extract (some studies<br />

show effect of culture broth and biomass)


Armillaria mellea (Honey Mushroom)


Armillaria mellea<br />

• High levels of polysaccharides<br />

• Anti-aging<br />

• Immune modulating<br />

• Antibiotics have been isolated (activity v Staph, Strep,<br />

Enterococcus, yeast and other fungi)<br />

• Neurological – Meniere’s syndrome, vertigo, epilepsy,<br />

neurasthenia, and HTN<br />

• Not readily available commercially


Auricularia auricula (Judas’ Ear/ Wood Ear)


A. auricula<br />

• Grows widely throughout US, Asia and<br />

Europe<br />

• Found easily fresh and dried in Asian markets<br />

• As with other jelly fungi, has high levels of<br />

polysaccharides<br />

• Functional food for elderly – developed as an<br />

additive for bread


Auricularia auricula (Judas’ Ear)<br />

• Anti-inflammatory – calms irritated mucous membranes<br />

• Antioxidant – both phenols and polysaccharides<br />

• Anti-thrombotic – inhibits platelet aggregation (in vivo and<br />

in vitro)<br />

• Anti-cholesterol – lowers total cholesterol, triglycerides<br />

and LDL (rat study)<br />

• Cardio protective – enhance SOD and decreases lipid<br />

peroxidation


A. auricula<br />

• Polysaccharides are key component<br />

• Dose: 2-3 g/day of HWE polysaccharides<br />

• Caution: patients on anti-coagulant Rx;<br />

patients trying to conceive (anti-fertility<br />

action)


Cordyceps sinensis


Cordyceps sinensis<br />

• Also called “caterpillar fungus”<br />

• Got world-wide attention in 1993 when Chinese runners broke nine world<br />

records – coach said were taking Cordyceps-based tonic<br />

• Increases energy levels and endurance<br />

• Mountain climbers use to reduce altitude sickness (oxygenates blood)<br />

• Has become one of the top-selling sports supplements among elite<br />

athletes<br />

• Used in elderly in China as “super-ginseng”<br />

• Cs-4 is cultivated strain<br />

Stengler, Mark, ND. <strong>The</strong> Health Benefits of Medicinal <strong>Mushrooms</strong>. 2005


Cordyceps sinensis<br />

• Can interrupt RNA/DNA synthesis – use as<br />

reverse transcriptase inhibitor, Tx HIV and<br />

hepatitis (AZT/Retrovir, Videx and Epivir)<br />

• Anti-aging – Cs-4 shown to increase oxygen<br />

uptake, aerobic capacity and resistance to<br />

fatigue


Cordyceps and fertility<br />

• Sexual Function – increases male sex hormones,<br />

sperm quality and quantity (in vitro affects<br />

signal transduction pathway of steroidogenesis)<br />

• Fertility – benefits female fertility and success<br />

of IVF (also increases libido)


Cordyceps sinensis<br />

• Stimulates 17β-estradiol production, through<br />

increased StAR (steroidogenic acute<br />

regulatory protein) and aromatase expression<br />

• Potential for management of<br />

postmenopausal osteoporosis


Cordyceps sinensis<br />

• Diabetes – Inc. insulin and sensitivity of cells to it (1 study<br />

95% of pt. on 3g/day C. sinensis biomass saw improved blood sugar, compared to 54% of those Tx with<br />

other methods.<br />

• Hepatoprotective – Tx alcohol-induced liver steatosis; 14 pts – 70% dec. in<br />

AST, 63% dec. in ALT and 64% dec in GGT over 3 month period (biomass)<br />

• Kidney protective – Tx chronic nephritis, kidney failure,<br />

chronic pyelonephritis, and protects v chemicals that<br />

are toxic to kidneys, increase in creatinine clearance &<br />

reduction in BUN


Cordyceps sinensis<br />

• Cardiovascular – arrhythmias, ischemic heart disease, and chronic<br />

heart failure,<br />

• Lipids – lowers cholesterol, LDL and VLDL and increases HDL<br />

• Animal studies show Cordyceps can dilate coronary arteries and<br />

increase blood flow to the heart<br />

• Respiratory – shown to be beneficial for asthma and COPD<br />

• Cancer – cordycepin (nucleoside derivative) induces apoptosis,<br />

inhibits NF-kB and increases Th1 promoting cytokines


Cordyceps sinensis<br />

• Dosage – 800-2400 mg of hot water/ethanol<br />

extract from fermented mycelia of Cordyceps<br />

sinensis, strain Cs-4, w/ min 14% polysaccharide,<br />

6% cordycepic acid, and 0.15% adenosine (Take<br />

1-3 400mg caps bid on empty stomach)<br />

• Safety – very safe; avoid in organ transplant<br />

patients using immunosuppressive agents


Grifola frondosa (Maitake)


Grifola frondosa (Maitake)<br />

• Valued in Japan as both food and medicine<br />

• Maitake in Japanese means “dancing mushroom”<br />

• Long used as an adaptogen<br />

• 1984 – maitake fraction discovered that stimulates<br />

macrophages<br />

• MaitakeGold 404 – enhance damaging activity of NK cells<br />

against cancer cells and change the NK precursor cells into<br />

activated NK cells


Grifola frondosa in Cancer<br />

• U Mass at Amherst found significant inhibitory activity v<br />

human cervical cancer and T4 leukemic cells<br />

• Improves chemotherapy by 12-28%<br />

• Nanba et al reported MD-fraction w/ fruiting body powder in<br />

CA patients who’d d/c’d chemo dt side effects: improvement<br />

in 7 of 12 liver CA pts, 11 of 16 breast CA pts, and 5 of 8 lung<br />

CA pts<br />

Can Maitake MD-fraction aid cancer patients? Kodama N, Komuta K, Nanba H. Alt Med Rev. 2002;(7)3:236-9


Grifola frondosa (Maitake)<br />

• Reduces Chemo Side Effects – reduced adverse<br />

rxn such as hair loss, pain, and nausea as well as<br />

diminished pain from end stage cancer<br />

• Diabetes – some animal studies; also small human study showed BG lowering<br />

• Cholesterol – high dose, mostly animal studies<br />

• Hypertension


Grifola frondosa (Maitake)<br />

• Dosage – 300-2400 mg hot water extract daily,<br />

w/ min of 20% polysaccharide (beta-glucan). 1-4<br />

(400 mg) capsules bid, empty stomach.<br />

• D-fraction/MD-fraction oral dose 35-150mg/day<br />

• Safety- very safe; avoid in organ transplant<br />

patients using immunosuppressive agents


Hericium erinaceus (Lion’s Mane)


Hericium erinaceus (Lion’s Mane)


Hericium erinaceus (Lion’s Mane)<br />

• “Nature’s nutrient for Neurons” dt stimulation of nerve growth<br />

factor (NGF)<br />

• Low levels of NGF linked to early Alzheimers and dementia<br />

• Dementia – improvement in mild dementia in 6 of 7 pts (consumed 5<br />

g/day H. erinaceus fruiting body in soup)<br />

• A randomized study – 30 pts (age 50-80 w/ mild dementia) 3 g/day<br />

tablets – increased cognitive function in Tx group<br />

Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive<br />

impairment: a double-blind, placebo controlled clinical trial. Mori, K. et al. Phytother Res. 2009;23(3)


H. erinaceus (Lion’s Mane)<br />

• MS – improved myelination in vitro; NGF suppresses<br />

immune-mediated inflammation<br />

• Neuropathy – low NGF linked to sensory neuropathy<br />

• Nerve damage – quicker recovery from nerve injury (rats)<br />

• MRSA – pts in Japan cleared of MRSA via H. erinaceus in<br />

diet<br />

• Gastritis – ABx and protects mucosa (human and rat studies)


H. erinaceus Dosage/Food Ideas<br />

• 3-5 g/day dried fruiting body to increase NGF<br />

• Chinese Pharmacopoeia 25-50g/day – studies<br />

on gastric ulcers would be equal at 500mg/kg<br />

• Consider long-term using in foods – soups, etc<br />

• Caution: asthma/allergies; potential<br />

hallucinogenic properties


Inonotus obliquus (Chaga)


Inonotus obliquus (Chaga)


Inonotus obliquus (Chaga)<br />

• Found in forests of Eastern Europe and Russia, mostly on<br />

white birch (Betula pubescens – tree of life and fertility in<br />

local myths)<br />

• Traditional use was a tea – used to Tx inoperable breast<br />

cancer, hip, gastric, parotid, pulmonary, stomach, skin,<br />

rectal and Hodgkin's disease<br />

• Betulinic acid (a triterpene) is key component (also high in<br />

bark of birch trees<br />

Powell, Medicinal <strong>Mushrooms</strong>: A Clinical Guide, 2010.


I. obliquus: Betulinic acid<br />

• Induces mitochondrial apoptosis in some<br />

cancer cell lines<br />

• Inhibits the enzyme topoisomerase (affects<br />

DNA replication)<br />

• Anti-retroviral<br />

• Anti-parasitic & anti-inflammatory


I. obliquus: Betulinic acid & Cancer<br />

• In vitro studies show activity against cancer<br />

cells: human melanoma, malignant brain<br />

tumors, ovarian cancer, head and neck<br />

squamous cell tumors<br />

• In vivo (rodent) studies confirm anti-cancer<br />

activity and no systemic toxicity<br />

Betulinic acid, a natural compound with potent anticancer effects. Mullauer<br />

et al. Anticancer Drugs. 2010.


Inonotus obliquus (Chaga)<br />

Antioxidant


Inonotus obliquus (Chaga)<br />

• Dose – Aqueous extract (prepared by<br />

decocting, as used traditionally) show anti-<br />

cancer effect<br />

• 2-5 g/day<br />

• Anti-oxidant activity – Phenolic extract


Lentinus edodes (Shiitake)


Lentinus edodes (Shiitake)<br />

• Gourmet food in the West, and important<br />

ingredient in Asian cuisine, w/ annual<br />

production (2 million tons) 2 nd only to<br />

common button mushroom<br />

• Excellent nutritional profile w/ high levels of B<br />

vitamins and pro-vitamin D2


Lentinus edodes (Shiitake)<br />

• LEM – a crude mycelial extract w/<br />

immunomodulating activity - glycoproteins,<br />

nucleic acid derivatives, vitamin B compounds<br />

& ergosterol<br />

• Lentinan – polysaccharide - is licensed in<br />

Japan to Tx gastric CA


Lentinus edodes (Shiitake)<br />

• Other compounds found in L. edodes:<br />

• Eritadenine – cholesterol lowering<br />

• Lentin – anti-fungal, inhibits reverse<br />

transcriptase (HIV, leukemia)


Lentinus edodes (Shiitake): Cancer<br />

• Advanced gastric cancer (review of 5 clinical<br />

trials, 650 patients)<br />

• Lentinan at 2 mg/week in addition to chemo<br />

increased survival and decreases chemo side<br />

effects<br />

• Usually given via injxn, but oral bioavail. too.


Lentinus edodes (Shiitake): Cholesterol<br />

• Eritadenine – accelerates excretion of<br />

ingested cholesterol<br />

• Initially levels thought too low in whole<br />

shiitakes, but new research shows higher<br />

levels, may help when pts show statin<br />

intolerance


Lentinus edodes (Shiitake): Hepatitis B<br />

• LEM (extracted polysaccharides)<br />

hepatoprotective<br />

• Study of 40 pts w/ chronic Hep B<br />

• 6 g/day for 4 months<br />

• Improved liver function<br />

• 17 pts became seronegative for Hbe antigen<br />

Yap et al, <strong>The</strong> medicinal benefits of Lentinan (B-1, 3-d glucan) from Lentinus edodes<br />

(Shiitake mushroom) through oral administration. Int J Med Mushr. 2005.


Lentinus edodes (Shiitake)<br />

• HIV – LEM increased T-cell count in HIV pts<br />

from 125o/mm3 to 2550/mm3 after 60 days<br />

• Candida – in vitro studies show highest anti-<br />

candida action among mushroom species


Lentinus edodes (Shiitake)<br />

• Active constituents – polysaccharides<br />

• Dosage – 800-3000 mg of hot water extract daily, w/ min<br />

10-20% polysaccharide (beta-glucan)<br />

• 1-5 capsules daily, morning and evening, on empty<br />

stomach<br />

• Safety – extracts lentinan and LEM are very safe. Rare<br />

sensitivity reports dermatitis. Caution in pts w/ sensitive<br />

skin.


Pleurotus ostreatus (Oyster mushroom)


Pleurotus ostreatus (Oyster mushroom)


Pleurotus ostreatus (Oyster mushroom)<br />

• Well-known as culinary mushroom<br />

• Contains lovastatin (0.7-2.8% dried weight)<br />

• Cholesterol - decreased VLDL 65-80% & total lipids<br />

40% in hamsters fed high fat diet<br />

• Negates elevation in triglycerides and chol. associated<br />

w/ chronic alcohol intake<br />

• May suppress appetite, reduce lipids in diabetic pts.


Pleurotus ostreatus (Oyster mushroom)<br />

Anti-aging:<br />

• Increase activity of catalase, superoxide<br />

dismutase, & glutathione peroxidase<br />

• Helps prevent decline in levels of Vitamins C<br />

and E associated with aging


Pleurotus ostreatus (Oyster mushroom)<br />

• Dose: 2-3 g/day polysaccharide (hot water)<br />

extract<br />

• Dose for cholesterol lowering: 10-15 g/day dried<br />

fruit body<br />

• Caution in patients taking protease inhibitors<br />

such as ritonavir, indinavir (may raise statin<br />

levels)


Trametes versicolor/Coriolus<br />

versicolor (Turkey Tail)


Trametes versicolor/Coriolus<br />

versicolor (Turkey Tail)


Trametes versicolor/Coriolus<br />

versicolor (Turkey Tail)<br />

• Most well-studied mushroom extract in the<br />

world<br />

• Leading anti-cancer drug derived from this<br />

mushroom: PSK (Krestin)<br />

• PSP & PSK – polysaccharide complexes


Cancer<br />

Trametes versicolor/Coriolus<br />

versicolor (Turkey Tail)<br />

• Stomach Cancer – PSK inc. survival times at all stages<br />

• Colorectal cancer – PSK inc. 5 yr & 8 yr survival post<br />

surgery and chemotherapy<br />

• Lung cancer (stages I-III) – PSK inc. 5 yr survival 2-4x<br />

• Esophageal – PSK inc 5 yr survival post surgery, radiation<br />

and chemo; PSP significant inc in 5 yr survival and<br />

improved quality of life


Trametes versicolor/Coriolus<br />

versicolor (Turkey Tail)<br />

• Nasopharyngeal – PSK inc. 5 yr survival (but not disease<br />

free period after chemo and radiation)<br />

• Breast cancer – mixed evidence; PSK inc survival in<br />

estrogen receptor negative CA; Pts w/ HLA B40 100%<br />

survival after 10 yrs<br />

• Cervical/uterine cancers– PSK (3-6 g/day) w/ radiation<br />

improved survival and increased sensitivity of CA to<br />

radiation


T. versicolor/C. versicolor<br />

• HIV – PSK in vitro anti-HIV via several routes<br />

• Herpes – clinically reduce frequency of HSV<br />

outbreaks<br />

• Chronic Fatigue Syndrome – biomass shows<br />

immune system activation and increased NK<br />

cell activity


Trametes versicolor/Coriolus<br />

versicolor (Turkey Tail)<br />

• Key component: polysaccharides<br />

• Dose: 3 g/day (3-6 g/day for cancer)<br />

• Immune deficiency: biomass 3 g/day (for<br />

cancer 15 g/day)


References<br />

• Couto, Silva. Evaluation of Coriolus versicolor Supplementation in HPV patients. Clinical Journal of Mycology. Feb<br />

2007. Vol. 2 (2-11).<br />

• Godoy, Stephanie – research assistant<br />

• Hetland, G. E. Johnson, T. Lyberg, S. Bernardshaw, A. M. A. Tryggestad & B. Grinde Effects of the Medicinal<br />

Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer Scand J Immunol. 2008 Oct;68(4):363-70.<br />

doi: 10.1111/j.1365-3083.2008.02156.x<br />

• Kelly-Pieper, Kelly et al. Safety and tolerability of an antiasthma herbal formula (ASHMI) in adult asthmatics: a<br />

randomized, double-blinded, placebo-controlled, dose escalation phase I study. J Altern Compliment Med. 2009<br />

July: 15(7)735-743.<br />

• MycoHerb. Clinical Guide for Practitioners. (Crane Herb Company) 2008<br />

• Pop, Otakar, et al. Beta glucans in higher fungi and their health effects. Nutrition Reviews. 209. Vol. 67(11)624-631.<br />

• Powell, Martin. Medicinal <strong>Mushrooms</strong>: A Clinical Guide. 2010<br />

• Solomon. Biology 9e, 2010, Chapter 29, <strong>The</strong> Fungi.<br />

• Stengler, ND, Mark. <strong>The</strong> Health Benefits of Medicinal <strong>Mushrooms</strong>. Basic Health Publications. 2005.<br />

• Upton, Roy, Editor. American Herbal Pharmacopoeia and <strong>The</strong>rapeutic Compendium. Reishi Mushroom.<br />

Ganoderma lucidum. April 2006.


Contact<br />

Sara Thyr, ND<br />

Willowbend Natural Medicine<br />

www.DrThyr.com<br />

707-780-6033<br />

sara@DrThyr.com

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