Fungal Pharmacy

December 2, 2017 | Author: Antoni Gandia | Category: Fungus, Plants, Immune System, T Helper Cell, Chemotherapy
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Mushrooms: Our Fungal Pharmacy Sara Thyr, ND

Fungi Characteristics • 100,000 described species

• Mycologists estimate may be more than 1.5 million species

• Classified in kingdom Fungi (eukaryotic) • Can grow to enormous size – 1500 acres

Fungi • Are decomposers • Absorb nutrients from their environment • Break down organic matter from dead organisms, leaves, garbage and other waste • When break down organic compounds, are released into environment where are recycled

Form vital symbiotic relationships • Most terrestrial plants have fungal partners • Live in close association with roots • Help plants obtain phosphate ions and other minerals from the soil • Lichens are symbiotic relationship of fungi and algae or cyanobacteria

How fungi get nutrients • Like animals, fungi are heterotrophs • Absorb food from environment (preformed carbon molecules) • Infiltrate a food source and secrete digestive enzymes onto it • Rapidly converts nutrients into new cell material

Structure - chitin • Cell walls contain chitin (a complex carbohydrate) • Chitin is also component of external skeletons of insects and other arthropods • Chitin is resistant to breakdown by most microorganisms


Structure • Fungi contain network of filaments • Multicellular body contains long, branched threadlike

filaments called hyphae • As hyphae grow, a tangled mass or network called mycelium is formed

• Spores (for those w sexual reproduction) produced on fruiting structures (sporangia - familiar part of mushroom is fruiting body)

Life cycle of fungi

Controversy in classification • Fungi are more closely related to animals than plants! • Like plants: have cell walls & vacuoles, are sessile; many inhabit the soil • Unlike plants: fungal cell walls do not contain cellulose (rather contain chitin – as in insect skeletons) • Fungal mode of nutrition differs from plants – cannot produce their own organic materials • Like animals, fungi are heterotrophs • Like animals, fungi have plate-like cristae in their mitochondria • Based on structural characters and molecular data, systematists now view fungi as more closely related to animals than to plants

5 Main Fungal Phyla

Glomeromycetes are symbionts with plant roots

• Form intracellular association with roots of most trees and herbaceous plants

• Assn. between hyphae of fungi and roots of plants are called mycorrhizae • Mutualistic symbiotic association – both benefit

Ascomycetes • 32,000 species • Great impact on humans

• Make cheeses, bake bread, and eat (morels and truffles) • Produce antibiotics • Form mycorrhizae with tree roots

• 40% join with algae or cyanobacteria to form lichens • Negative side: cause most fungal diseases of plants and animals

Basidiomycetes • Over 30,000 species • Largest and most familiar of the fungi

• Many are decomposers that obtain nutrients by breaking down organic matter • Mushroom is formed as fruiting body – more formally –

basidiocarp • Lower surface of the cap consists of many gills where basidiospores form


Ecological importance • Free-living decomposers – absorbing nutrients from organic wastes and dead organisms • Degrade cellulose and lignin, the main components of plant cell walls • Release water, CO2, and minerals – which are recycled • Without this continuous decomposition, essential nutrients would remain locked up in huge mounds of animal carcass, feces, branches, logs and

leaves • The nutrients within them would not be unavailable for use by new generations of organisms • Life would eventually cease!!!

Symbiosis • Important symbiotic relationships w/ animals, plants, bacteria

• 3-way symbiotic relationship w a fungus, a grass and a virus has recently been reported • In geothermal hot spots of Yellowstone

• When has specific virus, fungus is heat tolerant and confers this to the grass (when virus not present, no heat tolerance)

Get along well w/ others • More than 200 species of ants farm fungi • 80% of plants have mycorrhizae • Many cannot grow well without their fungal partners

• Improve soil by decreasing water loss and erosion • Can reclaim soils damaged by pollution • Mycorrhizae can modify toxic heavy metals, such as cadmium, so that plants cannot absorb them

Bioremediation • Some fungi can biodegrade pesticides, herbicides • Some break down coal tars and petroleum • Convert into CO2 and their basic elements • Fungi and bacteria can decontaminate farm land and clean up oil spills

Fuel Impact • Renewable fuel companies are researching fungi for fuel production • Recently a fungus was discovered than synthesizes 55

hydrocarbons, perhaps to inhibit growth of other organisms • Researchers may be able to use the genes of this fungus to

engineer other microorganisms to efficiently produce fuel

Fungi in Medicine • 1928 – Alexander Fleming discovered penicillin produced by the mold Penicillium notatum

• Other Rx from fungi: cephalosporin ABx, statins, and cyclosporine

• Claviceps purpurea infects rye and produces ergot – used to induce labor, stop uterine bleeding, treat HTN, and some migraines.

Penicillium conidiophores

Yummy! • Yeasts produce ethyl alcohol and carbon dioxide from sugars – beer and bread!!!

• Roughly 200 species are edible (roughly 30 are found in supermarkets) • Cheeses such as Roquefort, Brie and Camembert not

possible without species of Penicillium (the blue spots are masses of conidia) • But – watch out for the 70 poisonous species

Death cap (Amanita phalloides)

Medicinal Mushrooms • Have been used in Chinese medicine for thousands of years • Western researchers are starting to catch on • Myriad mushrooms to discuss

Properties • Plant cell walls made of cellulose, beta 1-4

linked glucose molecules • Fungi cell walls made of chitin, beta 1-3

linked polysaccharide chain (1-3 , 1-6 bglucan

Fungal beta glucan

Beta glucans • Yeast and oats also form beta glucans • Structure of mushroom beta glucans is more diverse • Therefore have higher levels activity in immune system • Mushroom polysaccharides have immunological activity – 77.5% from mushroom fruiting body – 20.8% from mycelium – 2.0% from culture filtrate (broth)

Active properties • Proteins • Tripterpenes • Sterols • Chitin • Enzymes • Polysaccharides!! Most widespread

Proteins • Ling Zhi-8 (LZ-8) from Ganoderma lucidum (Reishi) • Fve, EA-6 and Flammulin from Flammulina velutipes (Enokitake) • Immune modulation – act on monocytes; effect T-cell activation • Ribosome inactivation • Anti-HIV – Velutin inhibits HIV reverse transcriptase • Anti-fungal • Nuclease activity • Lectins have been isolated from many mushrooms, including F. velutipes, Grifola frondosa and G. lucidum.

Triterpenes • Families of ganoderic and lucidenic acids from Ganoderma lucidum are best known, give it many therapeutic properties

• Including: anti-cancer, anti-inflammatory, anti-histamine, hypotensive and sedative actions • Betulinic acid from Birch trees, taken up by Inonotus obliquus

(Chaga) – anti-cancer, anti-inflammatory, and anti-viral • Antrodia camphorata – unique Taiwanese mushroom – high levels of triterpenes

Sterols • Principal sterol is ergosterol, with H. erinaceus fruiting body containing high amounts • Anti-tumor activity has been shown, as well as anti-angiogenic properties Isolation of an antitumour compound (Ergosterol) from Agaracus blazei Murill and its mechanism of action. Takaku T, Kimura Y, Okuda H. J Nutr. 2001;131:1409-1413

• Anti-aging activity on par with resveratrol Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene Weng Y, Xiang L, Matsuura A, Zhang Y, Huang Q, Qi J. Biorreg Med Chem. 2010;18(3):684-1002

Chitin • Primary component of fungal cell walls • Effects on innate and adaptive immune responses • Ability to recruit and activate innate immune cells

• Can induce cytokine and chemokine production • Anti-bacterial and antioxidant activity • However is component of allergy-triggering allergens – including those in shrimp, crab and house dust mite

Enzymes • Digestive enzymes (proteases, lipases, etc.) • Antioxidant enzymes (laccase, catalase, superoxide dismutase [SOD]) • SOD is acid-labile - no bioactivity • Tyrosinase – genoprotective effect in vitro

Polysaccharides – Key to Immune activity

• Most widespread and most immunologically important • Profound impact on immune system

• Mediated by a number of fungal polysaccharide-specific receptors on surface of several immune cell types • Key immune cells are hard-wired to respond to the

presence of fungal polysaccharides • Immune system most likely evolved under constant challenge of fungal pathogens

Immune system activation by fungal beta glucans

Fungal Polysaccharides Effect on Immune System • Increase antibody production • Increase lymphocyte activating factor (IL-1) production • Increase tumor necrosis factor production • Increase colony stimulating factor production • Increase complement C3 production • Increase IFN-gamma production • Increase IL-2 production • Reduction in the level of IL-2 needed to produce a cytotoxic response • Th1 activation

Immune response (cont.) •

Macrophage activation

Neutrophil activation

Cytotoxic T-cell activation

Lymphokine activated killer cell proliferation

Enhanced maturation and tumor infiltration of dendritic cells

Th2 suppression

Reduce IL-4 production

Inhibit prostaglandin synthesis

Inhibit delayed type hypersensitivity

Powell, Martin. Medicinal Mushrooms: A Clinical Guide. Mycology Press. 2010.

Shift for Chronic Health Dso. • Mushroom polysaccharides promote shift in pattern of immune response

• Cancer, auto-immune disorders, allergic health conditions • Shift from pro-inflammatory, Th2 dominant to cytotoxic, Th1 dominant

• Increases especially critical are in Th1 cytokines such as IL2, IFN-y • Decrease in Th2 cytokines such as IL-4

Extraction Process • Hundreds of mushroom products on shelves • Most research done on hot water extracts • Or hot water extracts w/ alcohol extract

• Know what the process is for extraction • Human GI tract cannot break down chitin

Fruiting body or Conk • Fruiting body has highest level of different polysaccharides v mycelium or culture broth

• Conk – sterile fungal growth on tree trunk (Inonotus obliquus) • Triterpenes in G. lucidum higher in fruiting body • Antrodia camphorata data show triterpenes in biomass 40% of that

in fruiting body • Biomass products tend to have leftover substrate, not just mycelium

Extracts • Aqueous extracts (traditional teas/decoctions) give high polysaccharide concentrations but lower levels of triterpenes

• Ethanol (alcohol) extracts yield more triterpenes but fewer polysaccharides • Some companies do both processes and combine in products • Extracts preferred in cases of gut dysbiosis or impaired ability to break down whole mushroom or biomass products

Spores • Fruiting body exists to spread spores in reproduction • Rich in fatty acids, which have some therapeutic action • G. lucidum spores v fruiting body show little difference in immunological activity

Mycelium (liquid/submerged fermentation) • Liquid fermentation is used in pharm industry to produce antibiotics (also fungal enzymes)

• Controlled situation for nutrients and temperature to get most of desired components • Mycelium easily harvested from liquid and processed into

extracts (PSK & Lentinan) • Metabolites secreted into broth may also be harvested (Schizophyllan – from Schizophyllum commune)

Mycelial Biomass (solid state fermentation) • Mushroom culture is inoculated into sterile, grain-based substrate

(brown rice) • Once substrate is exhausted and about to produce fruiting bodies, mass of mycelium and residual substrate is dried and granulated

• Extract contains antibiotics, exopolysaccharides, enzymes, antioxidants (catalase, SOD) and substrate breakdown products arabinoxylans (have own therapeutic value) • Examples are Biobran, MGN-3 (shitake digested rice bran) and Avemar (yeast digested wheat germ) • Have range of bioactive molecules, but key immunomodulating beta-glucans and related polysaccharides are low

Side Effects/CI • Large-scale studies show minimal side effects • None serious (rash, redness, nausea) • Bowel changes in a few patients, resolves in 2-3 days

• Avoid in patient w/ mushroom allergy • Avoid in patients on Coumadin or heparin (some have blood thinning properties) • Avoid in patients with Hx organ transplant

Ideal Medicinal Mushrooms • Agaricus brasiliensis/Agaricus blazei • Armillaria mellea

• Auricularia auricula • Cordyceps sinensis

• Ganoderma lucidum (Reishi) • Grifola frondosa (Maitake)

Medicinal Mushrooms • Hericium erinaceus (Lion’s Mane) • Inonotus obliquus (Chaga) • Pleurotus ostreatus (Oyster mushroom) • Trametes versicolor/Coriolus versiclor (Turkey Tail)

G. lucidum

Ganoderma lucidum (Reishi) • Swiss Army Knife of mushrooms • Hx use over 2000 years

• “Ten-thousand-year mushroom” • “Mushroom of immortality” • “Herb of Spiritual Potency” • Traditional use by Taoist monks to promote centered calmness, improve meditative practices and attain a long and healthy life • Revered in Japanese culture – considered the most important of all

medicinal mushrooms

G. lucidum • Polysaccharides and triterpenes provide medicinal action • Chitin contributes to hardness of Reishi • Must do decoction to extract medicinal benefits

• Boil 2-15 g of chopped or powdered Reishi mushroom in 2L water, until 2/3 of water is reduced • Macerate 90 g chopped or powdered Reishi in 500 ml rice wine

for 10 days American Herbal Pharmacopoeia & Therapeutic Compentdium. Reishi Mushroom. Ganoderma lucidum. Standards of Analysis, Quality Control, and Therapeutics. Ed: Roy Upton. April 2006

G. lucidum • Very high polysaccharide and triterpene – over 130 compounds have been isolated in families of ganoderic and lucidenic acids • Fruiting bodies contain 41% beta glucan • Is an adaptogen

G. lucidum Health Benefits seen from ganoderic and lucidenic acids:

• Inhibit histamine release

• Anti-tumor

• Inhibit viral induction

• Inhibit cholesterol synthesis

• Hepatoprotective

• CNS sedation

• Antioxidant

• Anti-inflammatory

• Anti-hypertensive (ACE inhibiting)

• Anti-microbial • Induce apoptosis • Immune modulation

G. lucidum in Cancer • Long Hx traditional Tx of cancer, credited w many cases of spontaneous remission

• Triterpenes cytotoxic to many cancer cell lines • Inhibit nuclear transcription factor NF-kappaB • This particularly important v breast and prostate CA as

important in hormone independent growth • Increase NK cell activity and Th1 cytokine and decrease TH2 cytokine levels in advanced lung cancer patients

G. lucidum in athletes

• Hot water extracts have been shown to have anti-inflammatory effects equal to 5 mg

hydrocortisone (220 mg Reishi extract)

G. lucidum in allergies • Suppression of tumor necrosis factor-alpha confers strong anti-inflammatory effects • Also suppression of IL-6, NO and PGE2 via NFKB signaling pathway • Component in Chinese formula shown to completely block anaphylactic reactions in mouse model of peanut allergy

Reishi and Liver Dz. • Tx hepatitis – triterpene component • Prevent hepatic fibrosis via inhibiting proliferation of hepatic stellate cells

Cardiovascular benefits Polysaccharides and triterpenes are:

• Hypolipidemic • Hypotensive • Anti-thrombotic

• Decrease chest pain and improve ECG • Decrease SOB and cardiac palpitation • Mild ACE inhibitory activity A phase I/II study of ling zhi mushroom Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetidae) extract in patients with coronary heart disease. Gao Y, Chen G. Dai X, Ye J, Zhou S. Int J Med Mushr. 2004;6(4):30

Other health conditions • Insomnia/anxiety – spirit mushroom, mental stabilization • Rheumatoid arthritis – immune modulatory and antiinflammatory; dec RA synovial fibroblasts (in vitro) (NFKappaB pathway)

• Anti-aging – traditionally to promote longevity, shown to inhibit betaamyloid synaptic toxicity (Alzheimer’s), broad spectrum cardiovascular, neurological and immune benefits

• Blood sugar control – elevates plasma insulin, enhances tissue utilization of glucose, enhance liver metabolism of glucose

G. lucidum dose and CI • Folk use in CA: 25-300g/day fruiting body decoction • Avg. concentration of 15:1 gives 2-20g/day of extract

(most practitioners use 3-6 g/day) • For other conditions 1-3 g/day are common • Triterpenes are alcohol soluble but ideal to do HWE 1st • Caution on anti-hypertensive and sedative meds; on anti-coagulant drugs

Agaricus brasiliensis/Agaricus blazei Murrill

Agaricus brasiliensis (Sun Agaric)

A. brasiliensis in Cancer • Quickly becoming very popular medicinal mushroom • Polysaccharide extracts have strong activity against lung and ovarian cancer, Ehrlich ascites cancer and sarcoma • Synergistic benefits with chemo- and radiotherapy • Decreased cachexia and promoted weight gain while reducing tumor size (rat cachexia model)

• Reduced chemotherapy related side effects in human volunteers (2008 study) including appetite loss, alopecia, emotional stability and general weakness • Most research is positive, a few studies have shown no effect

A. brasiliensis/Agaricus blazei Murrill • Anti-infective and Anti-tumor properties • Prevents side effects of chemo and radiation • Type of extract important in immune system effect • liquid mushroom drink (AbM, H. erinaceus, G. frondosa)

Effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer G. Hetland, E. Johnson, T. Lyberg, S. Bernardshaw, A. M. A. Tryggestad & B. Grinde Scand J Immunol. 2008 Oct;68(4):363-70. doi: 10.1111/j.13653083.2008.02156.x

A. brasiliensis & other conditions • Diabetes – decreases cholesterol and glucose levels • Allergies – reduces Th2 mediated allergic rxn (AndoSan) • Hepatoprotective – Tx hep B, reduced liver enzymes (20g

bid x 3 months) • Fruiting body extract are in most studies • Usual dose 3 g/day polysaccharide extract (some studies show effect of culture broth and biomass)

Armillaria mellea (Honey Mushroom)

Armillaria mellea • High levels of polysaccharides • Anti-aging

• Immune modulating • Antibiotics have been isolated (activity v Staph, Strep, Enterococcus, yeast and other fungi)

• Neurological – Meniere’s syndrome, vertigo, epilepsy, neurasthenia, and HTN • Not readily available commercially

Auricularia auricula (Judas’ Ear/ Wood Ear)

A. auricula • Grows widely throughout US, Asia and Europe

• Found easily fresh and dried in Asian markets • As with other jelly fungi, has high levels of

polysaccharides • Functional food for elderly – developed as an

additive for bread

Auricularia auricula (Judas’ Ear) • Anti-inflammatory – calms irritated mucous membranes • Antioxidant – both phenols and polysaccharides

• Anti-thrombotic – inhibits platelet aggregation (in vivo and in vitro) • Anti-cholesterol – lowers total cholesterol, triglycerides

and LDL (rat study) • Cardio protective – enhance SOD and decreases lipid peroxidation

A. auricula • Polysaccharides are key component

• Dose: 2-3 g/day of HWE polysaccharides • Caution: patients on anti-coagulant Rx;

patients trying to conceive (anti-fertility action)

Cordyceps sinensis

Cordyceps sinensis • Also called “caterpillar fungus”

• Got world-wide attention in 1993 when Chinese runners broke nine world records – coach said were taking Cordyceps-based tonic • Increases energy levels and endurance • Mountain climbers use to reduce altitude sickness (oxygenates blood) • Has become one of the top-selling sports supplements among elite athletes • Used in elderly in China as “super-ginseng” • Cs-4 is cultivated strain Stengler, Mark, ND. The Health Benefits of Medicinal Mushrooms. 2005

Cordyceps sinensis • Can interrupt RNA/DNA synthesis – use as reverse transcriptase inhibitor, Tx HIV and hepatitis (AZT/Retrovir, Videx and Epivir) • Anti-aging – Cs-4 shown to increase oxygen uptake, aerobic capacity and resistance to fatigue

Cordyceps and fertility • Sexual Function – increases male sex hormones,

sperm quality and quantity (in vitro affects signal transduction pathway of steroidogenesis)

• Fertility – benefits female fertility and success of IVF (also increases libido)

Cordyceps sinensis • Stimulates 17β-estradiol production, through

increased StAR (steroidogenic acute regulatory protein) and aromatase expression

• Potential for management of postmenopausal osteoporosis

Cordyceps sinensis • Diabetes – Inc. insulin and sensitivity of cells to it (1 study 95% of pt. on 3g/day C. sinensis biomass saw improved blood sugar, compared to 54% of those Tx with other methods.

• Hepatoprotective – Tx alcohol-induced liver steatosis; 14 pts – 70% dec. in AST, 63% dec. in ALT and 64% dec in GGT over 3 month period (biomass)

• Kidney protective – Tx chronic nephritis, kidney failure, chronic pyelonephritis, and protects v chemicals that

are toxic to kidneys, increase in creatinine clearance & reduction in BUN

Cordyceps sinensis • Cardiovascular – arrhythmias, ischemic heart disease, and chronic heart failure,

• Lipids – lowers cholesterol, LDL and VLDL and increases HDL • Animal studies show Cordyceps can dilate coronary arteries and increase blood flow to the heart

• Respiratory – shown to be beneficial for asthma and COPD • Cancer – cordycepin (nucleoside derivative) induces apoptosis, inhibits NF-kB and increases Th1 promoting cytokines

Cordyceps sinensis • Dosage – 800-2400 mg of hot water/ethanol extract from fermented mycelia of Cordyceps

sinensis, strain Cs-4, w/ min 14% polysaccharide, 6% cordycepic acid, and 0.15% adenosine (Take

1-3 400mg caps bid on empty stomach) • Safety – very safe; avoid in organ transplant patients using immunosuppressive agents

Grifola frondosa (Maitake)

Grifola frondosa (Maitake) • Valued in Japan as both food and medicine • Maitake in Japanese means “dancing mushroom”

• Long used as an adaptogen • 1984 – maitake fraction discovered that stimulates macrophages

• MaitakeGold 404 – enhance damaging activity of NK cells against cancer cells and change the NK precursor cells into activated NK cells

Grifola frondosa in Cancer • U Mass at Amherst found significant inhibitory activity v human cervical cancer and T4 leukemic cells

• Improves chemotherapy by 12-28% • Nanba et al reported MD-fraction w/ fruiting body powder in CA patients who’d d/c’d chemo dt side effects: improvement

in 7 of 12 liver CA pts, 11 of 16 breast CA pts, and 5 of 8 lung CA pts Can Maitake MD-fraction aid cancer patients? Kodama N, Komuta K, Nanba H. Alt Med Rev. 2002;(7)3:236-9

Grifola frondosa (Maitake) • Reduces Chemo Side Effects – reduced adverse rxn such as hair loss, pain, and nausea as well as diminished pain from end stage cancer • Diabetes – some animal studies; also small human study showed BG lowering • Cholesterol – high dose, mostly animal studies • Hypertension

Grifola frondosa (Maitake) • Dosage – 300-2400 mg hot water extract daily, w/ min of 20% polysaccharide (beta-glucan). 1-4 (400 mg) capsules bid, empty stomach. • D-fraction/MD-fraction oral dose 35-150mg/day • Safety- very safe; avoid in organ transplant patients using immunosuppressive agents

Hericium erinaceus (Lion’s Mane)

Hericium erinaceus (Lion’s Mane)

Hericium erinaceus (Lion’s Mane) • “Nature’s nutrient for Neurons” dt stimulation of nerve growth factor (NGF) • Low levels of NGF linked to early Alzheimers and dementia • Dementia – improvement in mild dementia in 6 of 7 pts (consumed 5 g/day H. erinaceus fruiting body in soup)

• A randomized study – 30 pts (age 50-80 w/ mild dementia) 3 g/day tablets – increased cognitive function in Tx group Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind, placebo controlled clinical trial. Mori, K. et al. Phytother Res. 2009;23(3)

H. erinaceus (Lion’s Mane) • MS – improved myelination in vitro; NGF suppresses immune-mediated inflammation

• Neuropathy – low NGF linked to sensory neuropathy • Nerve damage – quicker recovery from nerve injury (rats) • MRSA – pts in Japan cleared of MRSA via H. erinaceus in

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

H. erinaceus Dosage/Food Ideas • 3-5 g/day dried fruiting body to increase NGF • Chinese Pharmacopoeia 25-50g/day – studies on gastric ulcers would be equal at 500mg/kg • Consider long-term using in foods – soups, etc • Caution: asthma/allergies; potential hallucinogenic properties

Inonotus obliquus (Chaga)

Inonotus obliquus (Chaga)

Inonotus obliquus (Chaga) • Found in forests of Eastern Europe and Russia, mostly on white birch (Betula pubescens – tree of life and fertility in

local myths) • Traditional use was a tea – used to Tx inoperable breast cancer, hip, gastric, parotid, pulmonary, stomach, skin,

rectal and Hodgkin's disease • Betulinic acid (a triterpene) is key component (also high in bark of birch trees Powell, Medicinal Mushrooms: A Clinical Guide, 2010.

I. obliquus: Betulinic acid • Induces mitochondrial apoptosis in some cancer cell lines

• Inhibits the enzyme topoisomerase (affects DNA replication)

• Anti-retroviral • Anti-parasitic & anti-inflammatory

I. obliquus: Betulinic acid & Cancer • In vitro studies show activity against cancer

cells: human melanoma, malignant brain tumors, ovarian cancer, head and neck

squamous cell tumors • In vivo (rodent) studies confirm anti-cancer

activity and no systemic toxicity Betulinic acid, a natural compound with potent anticancer effects. Mullauer et al. Anticancer Drugs. 2010.

Inonotus obliquus (Chaga) Antioxidant

Inonotus obliquus (Chaga) • Dose – Aqueous extract (prepared by

decocting, as used traditionally) show anticancer effect

• 2-5 g/day • Anti-oxidant activity – Phenolic extract

Lentinus edodes (Shiitake)

Lentinus edodes (Shiitake) • Gourmet food in the West, and important ingredient in Asian cuisine, w/ annual

production (2 million tons) 2nd only to common button mushroom

• Excellent nutritional profile w/ high levels of B vitamins and pro-vitamin D2

Lentinus edodes (Shiitake) • LEM – a crude mycelial extract w/ immunomodulating activity - glycoproteins, nucleic acid derivatives, vitamin B compounds & ergosterol • Lentinan – polysaccharide - is licensed in Japan to Tx gastric CA

Lentinus edodes (Shiitake) • Other compounds found in L. edodes: • Eritadenine – cholesterol lowering • Lentin – anti-fungal, inhibits reverse transcriptase (HIV, leukemia)

Lentinus edodes (Shiitake): Cancer • Advanced gastric cancer (review of 5 clinical trials, 650 patients) • Lentinan at 2 mg/week in addition to chemo increased survival and decreases chemo side effects • Usually given via injxn, but oral bioavail. too.

Lentinus edodes (Shiitake): Cholesterol • Eritadenine – accelerates excretion of ingested cholesterol • Initially levels thought too low in whole shiitakes, but new research shows higher levels, may help when pts show statin intolerance

Lentinus edodes (Shiitake): Hepatitis B • LEM (extracted polysaccharides) hepatoprotective • Study of 40 pts w/ chronic Hep B • 6 g/day for 4 months • Improved liver function • 17 pts became seronegative for Hbe antigen Yap et al, The medicinal benefits of Lentinan (B-1, 3-d glucan) from Lentinus edodes (Shiitake mushroom) through oral administration. Int J Med Mushr. 2005.

Lentinus edodes (Shiitake) • HIV – LEM increased T-cell count in HIV pts from 125o/mm3 to 2550/mm3 after 60 days • Candida – in vitro studies show highest anticandida action among mushroom species

Lentinus edodes (Shiitake) • Active constituents – polysaccharides • Dosage – 800-3000 mg of hot water extract daily, w/ min

10-20% polysaccharide (beta-glucan) • 1-5 capsules daily, morning and evening, on empty stomach

• Safety – extracts lentinan and LEM are very safe. Rare sensitivity reports dermatitis. Caution in pts w/ sensitive skin.

Pleurotus ostreatus (Oyster mushroom)

Pleurotus ostreatus (Oyster mushroom)

Pleurotus ostreatus (Oyster mushroom) • Well-known as culinary mushroom • Contains lovastatin (0.7-2.8% dried weight)

• Cholesterol - decreased VLDL 65-80% & total lipids 40% in hamsters fed high fat diet • Negates elevation in triglycerides and chol. associated w/ chronic alcohol intake • May suppress appetite, reduce lipids in diabetic pts.

Pleurotus ostreatus (Oyster mushroom) Anti-aging:

• Increase activity of catalase, superoxide dismutase, & glutathione peroxidase

• Helps prevent decline in levels of Vitamins C and E associated with aging

Pleurotus ostreatus (Oyster mushroom) • Dose: 2-3 g/day polysaccharide (hot water) extract

• Dose for cholesterol lowering: 10-15 g/day dried fruit body

• Caution in patients taking protease inhibitors such as ritonavir, indinavir (may raise statin levels)

Trametes versicolor/Coriolus versicolor (Turkey Tail)

Trametes versicolor/Coriolus versicolor (Turkey Tail)

Trametes versicolor/Coriolus versicolor (Turkey Tail) • Most well-studied mushroom extract in the

world • Leading anti-cancer drug derived from this

mushroom: PSK (Krestin) • PSP & PSK – polysaccharide complexes

Trametes versicolor/Coriolus versicolor (Turkey Tail) Cancer • Stomach Cancer – PSK inc. survival times at all stages • Colorectal cancer – PSK inc. 5 yr & 8 yr survival post surgery and chemotherapy

• Lung cancer (stages I-III) – PSK inc. 5 yr survival 2-4x • Esophageal – PSK inc 5 yr survival post surgery, radiation and chemo; PSP significant inc in 5 yr survival and improved quality of life

Trametes versicolor/Coriolus versicolor (Turkey Tail) • Nasopharyngeal – PSK inc. 5 yr survival (but not disease free period after chemo and radiation)

• Breast cancer – mixed evidence; PSK inc survival in estrogen receptor negative CA; Pts w/ HLA B40 100% survival after 10 yrs

• Cervical/uterine cancers– PSK (3-6 g/day) w/ radiation improved survival and increased sensitivity of CA to radiation

T. versicolor/C. versicolor • HIV – PSK in vitro anti-HIV via several routes • Herpes – clinically reduce frequency of HSV

outbreaks • Chronic Fatigue Syndrome – biomass shows

immune system activation and increased NK cell activity

Trametes versicolor/Coriolus versicolor (Turkey Tail) • Key component: polysaccharides • Dose: 3 g/day (3-6 g/day for cancer) • Immune deficiency: biomass 3 g/day (for cancer 15 g/day)

References •

Couto, Silva. Evaluation of Coriolus versicolor Supplementation in HPV patients. Clinical Journal of Mycology. Feb 2007. Vol. 2 (2-11).

Godoy, Stephanie – research assistant

Hetland, G. E. Johnson, T. Lyberg, S. Bernardshaw, A. M. A. Tryggestad & B. Grinde Effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer Scand J Immunol. 2008 Oct;68(4):363-70. doi: 10.1111/j.1365-3083.2008.02156.x

Kelly-Pieper, Kelly et al. Safety and tolerability of an antiasthma herbal formula (ASHMI) in adult asthmatics: a randomized, double-blinded, placebo-controlled, dose escalation phase I study. J Altern Compliment Med. 2009 July: 15(7)735-743.

MycoHerb. Clinical Guide for Practitioners. (Crane Herb Company) 2008

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

Powell, Martin. Medicinal Mushrooms: A Clinical Guide. 2010

Solomon. Biology 9e, 2010, Chapter 29, The Fungi.

Stengler, ND, Mark. The Health Benefits of Medicinal Mushrooms. Basic Health Publications. 2005.

Upton, Roy, Editor. American Herbal Pharmacopoeia and Therapeutic Compendium. Reishi Mushroom. Ganoderma lucidum. April 2006.

Contact Sara Thyr, ND Willowbend Natural Medicine 707-780-6033 [email protected]

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