•9/3/2014

Medicinal as Functional Foods A Clinician’s Overview • Popularity high in Asia, just beginning in Europe Christopher Hobbs Ph.D., L.Ac., A.H.G. • North America—mushroom extracts sold without • Licensed Acupuncturist (primary health need of approval or registration care provider in California) • Most popular: shiitake, maitake, reishi, cordyceps, turkey tails; Agaricus blazei, Hypsizigus marmoreus • Clinical herbalist • Products available: mushroom mycelium powder • Research scientist, UC Berkeley (grown on grain, soybeans), powdered extracts in

• Author of Medicinal Mushrooms, other capsules or tablets; ethanolic extracts (with or without glycerin books on

Mushroom as Food, Green Health Benefits of Mushrooms Benefits • Very little fat, no cholesterol • Highly nutritious—oyster mushroom is 25% high- • Valuable mineral content; high trace minerals quality protein; vitamins, • High in vitamins, especially B vitamins minerals • Pleurotus provides a better supply of B • Turkey Tails, vitamins than any common food, except meat versicolor, produces • Great slimming food many enzymes used for detoxing toxic sites, • Cholesterol regulation! Shiitake, Pleurotus biobleaching of paper, • Very high in fiber—cellulose, lignan, chitin etc.

•1 •9/3/2014

Mineral Content of Fungi

Mushrooms as medicine • Medicine— approved drugs in Japan, China for cancer treatment adjuvants (with chemo) • Health supplements to support immunity

•2 •9/3/2014

Triple Helix of Biological Activity of Fungi beta (1-> 3) glucan • All fungi and yeasts have triple helix polysaccharides (beta-glucans) in cell walls • Heat breaks down chitin, exposes active molecules • Binding of large molecular weight fungal

compounds to gut receptors (60% of total) ß-(13)-D-glucan geometry – complex immune activation • Triple helix conformation might give flexibility to cell wall – Dectin, other receptors • Intact tertiary structure can confer increased immunomodulation • Alcohol, excessive heating could disrupt tertiary structures

Beta-glucans→Dectin Receptor Some Possible Indications

• Shiitake for immune weakness, infections • Shiitake, Turkey Tails for Cancer • Viral Syndromes: Hepatitis C, herpes, HIV • Cordyceps for fatigue, performance, “adaptogen,” antiaging supplement • Reishi for insomnia, anxiety, nervous

system disorders related to stress • Reishi for respiratory problems

Research Summary Therapeutic Use—Questions!

• More than 270 recognized species of • Mushroom products widely used, many countries mushrooms are known to have specific • Important questions immunotherapeutic properties – Whole mushrooms or isolated constituents? • Fifty nontoxic mushrooms species yielded – Smaller pieces of heteroglucans active? Alcohol, heat, potential immunoceuticals in vitro Hcl all reduce size of initial compounds • Six species have been studies in human – Fruit body, or mycelium more effective?

cancers – Fresh vs. dry J Society Integr Oncol. 2008 Summer; 6(3): 122–128 – Dose--too high a dose can lead to immune suppression, not high enough, immune activation may be incomplete

•3 •9/3/2014

More Questions Conclusion Clinical, Personal Use

• Common Questions • More controlled human clinical trials needed – Substrate: host species varies for most • Mushroom extracts are effective for counteracting some harmful effects of chemo and radiation – Specific scope of indications? • Counteract immune suppression – Duration of treatment? Will immune activation decrease with time? • Mushroom extracts can lead to increased survival times and improved quality of life – For cancer, more effective with radiation or ? Or alone? • Preliminary published research, as well as clinical reports show effectiveness for hepatitis C and other viral syndromes – Integration into modern health care—controlled studies are needed

Traditional Chinese Medicine Traditional Chinese Medicine II

• Historical medical use in Asia is often based on the • Most common species added to prescriptions precepts of traditional Chinese medicine (TCM) include – Hoelen, fuling (Wolfiporia cocos) • Mushroom species are often added to soups, traditional • Tonify Spleen system (digestion), remove excess water, foods and eaten regularly for immune support, other counteract fatigue, improve immune status healing qualities (over 3,000 years) – Zhuling (Grifola umbellatus) • Often added to prescriptions to treat “deficiency” or xu • Diuretic herb, remove excess water (edema), cancer – Ling zhi (Ganoderma lucidum) conditions of Kidney, Heart, Lung, Spleen systems • Calm “spirit,” for disturbed “shen,” respiratory ailments, panacea – Dong Chong Xia Cao (Cordyceps sinensis) • Exhaustion, sexual debility, to build “essence”

Most Clinically-Relevant Trametes versicolor Medicinal Mushrooms Turkey Tails

• Lentinus edodes Shiitake • Ubiquitous • Trametes versicolor Turkey tails on nearly every • Ganoderma lucidum Reishi continent • Grifola frondosa Maitake • Delignifies many • Wolfiporia cocos Hoelen, Fuling hardwoods, especially oaks; fruit trees • Pleurotus spp. Oyster mushroom • Prescription drugs in

• Cordyceps sinensis dong chong xia cao Japan for treatment of cancer with purified • Other interesting species: Agaricus blazei, Tremella protein-polysaccharide fuciformis, Inonotus obliquus, Heiricium??? complexes (PSP, PSK)

•4 •9/3/2014

Trametes versicolor Stereum spp. Turkey Tails False Turkey-Tails

• Zoned, hairy cap • Turkey tails: rough, white pore surface • Stereum: smooth orange pore surface • Grow in similar habitats on hardoods

Trametes versicolor Summary of Trametes versicolor cancer Clinical Trials Conducted in Asia

Type of Cancer No. of RCT Stomach 21-RCTs, N = 13,498 Colorectal 9 RCTs, N = 2,194 Esophageal 3 RCTS, N = 532 Breast 4 RCTs, N = 2,217

J Soc Integr Oncol. 2008 Summer; 6(3): 122–128.

Trametes versicolor PSK, PSP most-studied • PSK, PSP; crude extracts from T. versicolor • One medicinal mushroom, Tv, has been studied in • prepared from strain CM-101 of Tv by water phase I, II, and III randomized clinical trials extraction • Stomach, colorectal, esophageal, and breast cancer patients • 62% polysaccharide and 38% protein • Japanese and Korean clinical data provide support • proteoglycan molecules bioavailable orally for the hypothesis that immunomodulation can • Bioactive molecules found in bone marrow, influence the clinical course in various cancers salivary gland, brain, liver, spleen, pancreas, • Meta-analysis in 1,094 colorectal cancer patients, and tumor tissue within 24 hours (in vivo) all showing a positive impact on clinical outcomes (Sakamoto et al, 2006)

•5 •9/3/2014

Mushroom Research in U.S. Trametes versicolor mushroom immune therapy in breast cancer Bastyr University and University of Minnesota

2.4 million awarded for explore the feasibility for use of • “Data from multiple epidemiologic and clinical mushroom extracts as immunomodulating agents studies …. suggest that immune function has a

Trametes Versicolor in Women with Breast Cancer role in breast cancer prevention.” • Phase II randomized-placebo controlled trial of a mushroom • “Immune therapy utilizing the polysaccharide extract (Trametes versicolor or Tv) constituents of Trametes versicolor (Tv) as • Women with early stage breast cancer who have completed adjuvant radiation therapy concurrent adjuvant cancer therapy may be • Immune recovery—enhanced natural killer cell activity, etc. warranted as part of a comprehensive cancer • Self-reported quality of life/ fatigue scores treatment and secondary prevention strategy.” • On-going research for Breast, Prostate Cancer re-funded, 2011 • J Soc Integr Oncol. 2008 Summer;6(3):122-8.

Trametes versicolor Trametes versicolor Clinical Indications Dose, Side Effects

• PSK: – Cervical, gastric cancers, carcinoma of nasopharynx • Dose: 3-6 grams/day orally; i.v. – Glomerulonephritis, sarcoidosis, idiopathic nephrotic syndrome, lupus, chronic rheumatoid arthritis (Immune enhancement and improved administration clinical outcomes with such diseases) – Fewer outbreaks of genital herpes (increased cellular immunity) • Toxicity low, few reported side effects, – Hyperlipidemia (reduced LDL levels in stage IIa) even with i.v. administration. • PSP: – Cancers of the esophagus, stomach, and lung (controlled, 3 g/day p.o.) • Negative results were found on the with chemo- and radiation therapies: less side effects including anorexia, fatigue, pain; higher body weight; improved immune status. Ames and chromosome distortion tests – Esophageal cancer: higher remissions with PSP and chemo (72% vs. 42% on chemo alone).

Lentinus edodes Lentinus edodes Shiitake

• Xiang gu or • Biological Effects “fragrant mushrooms” of – Immunomodulating Chinese cuisine – Antitumor, anticarcinogenic • Second most widely – Antiviral cultivated – Hepatoprotective mushroom – Antiulcerogenic

• Most published – Anticholesterolemic scientific studies Fruiting body of shiitake on oak

•6 •9/3/2014

Lentinus edodes Lentinus edodes Clinical Trials • Summary of indications • Clinical trials summary – AIDS/HIV – Numerous Chinese, Japanese clinical trials with LEM – Hepatitis C, B (chronic) + chemo for various cancers – Cancer (prevention, • 5-year survival rate is up to 30% higher with LEM over treatment (often with placebo chemo, raditaion) – Antitumor effect, increase survival time for patients – Hypercholesterolemia with inoperable gastric cancer; with breast cancer – Chronic fatigue, viral (lentinan) syndromes – Best results seen in phase III trial when lentinan was – Immune suppression administered – Infectious diseases

Ganoderma lucidum Ganoderma lucidum Reishi, Ling Zhi (antler form) Biological Effects

• Ling zhi celebrated in • Analgesic (antinociceptive) • Cardiotonic • Antiallergic, antihistimine ancient Chinese art • Antithrombotic (G. • Antiinflammatory • Revered for several japonicum) thousand years to treat • Antibacterial • Antioxidant • Central depressant, liver disease, nervous peripheral anticholinergic system disorders, • Antitumor, antimutagenic respiratory tract infections • Antiviral (HIV, others) • Expectorant, antitussive • Modern research shows • Antihypertensive • Adrenocortical functions immunomodulating, • Immunostimulating • Hepatoprotective – Enhances bone marrow anticancer effects nucleated cell proliferation • Protection against ionizing – Enhanced NK cell activity radiation – Interleukin-1, -2 production • Antiulcer – Increase in WBC production

Ganoderma lucidum Ganoderma applanatum Traditional Indications, Dose Artist’s Conk

• Calms the spirit, augments the Heart qi, and tonifies the • Common Heart blood: for insomnia, fright and palpitations, and worldwide on forgetfullness associated with insufficient Heart qi and hardwoods blood • Pore surface turns • Failing to nourish the spirit. Can be used as a stand-alone brown when herb for this purpose scratched • Deficiency consumption, cough, wheezing, insomnia, and • Hepatoprotective poor digestion effect in patients

with post-hepatitis cirrhosis or chronic rd • Bensky et al (3 edition, 2004) hepatitis B

•7 •9/3/2014

Ganoderma lucidum Ganoderma lucidum Traditional Indications, Dose Clinical Indications • Anti-aging, antioxidant effect • Adjuvant for cancer treatment protocols • PROPERTIES sweet, neutral • Nervous system disorders: neurasthenia, dizziness, insomnia • CHANNELS ENTERED Heart, Liver, Lung (deficiency types--spirit or “shen” disturbance) • KEY CHARACTERISTICS calms the spirit while • Mental diseases, alzheimer’s disease augmenting the qi and nourishing the blood • Rhinitis, bronchitis, other chronic URIs; respiratory allergies • DOSAGE 3- 15g in decoctions; 1.5-3g in pills and • Duodenal ulcers powders • Hyperlipidemia • CAUTIONS & CONTRAINDICATIONS Use with • Diabetes caution in patients with excessive conditions. • Hepatitis

Therapeutic Dose: 3-12 grams fruiting body powder; 3-5 g powdered According to Bensky et al, extract

Ganoderma applalatum Ganoderma sinense • Traditionally used to treat deafness, afflictions of the • Clinical indications • Biological effects: joints, and to strengthen the – Urinary, respiratory • Immunostimulating "shen," or spirit tract infections • Antitumor activity • “Improves the complexion, – Tuberculosis against sarcoma 180, increase agility, and imparts – Esophageal cancer other tumors in mice longevity” – Post-hepatic cirrhosis • Substance with • Antiinflammatory, diuretic, and to improve stomach function – Chronic active interferon-like • Analgesic and antiinflammatory hepatitis properties induced from mouse spleen activity in arthritis models in mice cells • Mycelial extract promotes phagocytosis

Ganoderma tsugae Ganoderma tsugae

• Triterpenoids, • Fruiting bodies grow on lucidone A, old hemlocks ganoderic acid B, and ganoderic acid • Song shan ling zhi (pine C2 also in G. tree ) lucidum • Widely-cultivated in • Hepatoprotective activity in mice Taiwan • Antitumor effect • Increased serum interferon levels and augmented splenic NK cell activity in mice, i.p.

•8 •9/3/2014

Ganoderma curtisii Grifola frondosa Maitake • Yellow and orange- • Highly regarded in Japan capped species where people “danced” with joy when they found it • Grows in se U.S. • Prized as an edible in Europe, North America, Asia • Clinical studies sparse • Heavily promoted in N.A. and Asia as a

Grifola frondosa Grifola frondosa Clinical Indications, Dose Clinical Trials

Supportive treatment for: Controlled • Hypercholesterolemia • After an average follow-up of 71 months in 146 • Hypertension patients with bladder cancer treated by partial • Cancer, especially bladder cancer cystectomies, the recurrence rate was 33% • Hepatitis compared with 65% for controls (G. frondosa, zhu • Non insulin dependent diabetes, blood sugar imbalances ling)

Therapeutic dose: • 2 grams watery extract powder, 3 x daily • 3-12 grams powdered fruiting body

Wolfiporia cocos Wolfiporia cocos Hoelen, Fuling Clinical Trials • One of the most widely-prescribed herbal drugs in traditional Chinese • No clinical trials on W. cocos alone. medical prescriptions • Clinical reports: used to treat cardiac arrhythmias • Sliced and dried mushroom tuber or “sclerotium” or the skin is used in • Decoction of the skin studied in China for treating traditional medicine coughs, edema, as a diuretic. • The fungus infects the roots and • Used as an abortifacient in Korea stumps of pine and other conifers

• Range: eastern Asia, e. Australia, se North America, Africa • Used for food and medicine in Nigeria

•9 •9/3/2014

Wolfiporia cocos Cordyceps sinensis Clinical Indications, Dose Cordyceps, Dong Chong Xia Cao

• In traditional Chinese medicine • “Summer plant, winter – Increases urine output, clears dampness; difficult worm” urination, diarrhea, edema due to fluid stagnation • Formerly only available to – Symptoms such as anorexia, diarrhea, abdominal Chinese royalty; now distention (due to Spleen Qi deficiency and dampness) cultivated – Symptoms such as palpitations, headache, dizziness • Chinese Olympic running pal•pitations, headache, dizziness due to phlegm congestion team claimed success due to cordyceps – Heart palpitations, insomnia, headache, dizziness due to disturbance of the “Heart system” or shen (spirit) • Thought to promote stamina, sexual vitality Dose: 9-15 grams up to 60 grams; 2-4 grams extract

Cordyceps sinensis Cordyceps sinensis Clinical Trials Biological Effects

• Immunostimulating actions, in vivo Controlled: – Increased macrophage activity • Positive effects on hyperlipidemia compared with – Significantly increased survival span with lymphoma, in vivo controls – Increased platelet production • Reduced aminoglycoside nephrotoxicity in elderly – Stimulation of B-lymphocytes patients in a small (n=21] trial. – No effect on humoral immunity • – Methanolic extract suppressed IL-1beta, IL-6, TNF-alpha, and IL-8 cytokines

Uncontrolled: – Modulated TH1 and TH2 cell functions in bronchial airway • Reduction of cyclosporin nephrotoxicity in kidney- – Increases survival time of mice with lupus transplant recipients.

Cordyceps sinensis Cordyceps sinensis Biological Effects Clinical Indications, Dose

• Convalesence • Cardioprotective, in vivo • Antiaging – Positive inotropic and negative chronotropic effects, • Immunosuppession relaxation of aorta and bronchus (in vitro) • Asthma, bronchial and lung inflammation – Inhibition of thrombi formation and platelet aggregation • Adjuvant in protocols for treating cancer • Bronchodilation • Nephritis; nephrotoxicity in kidney-transplant patients induced by cyclosporin • Sedative, hypnotic • nephrotoxicity in elderly patients • MAO-inhibition • Hyperlipidemia • Antibacterial • Enhancement of liver ATP status in liver • Therapeutic dose: 3-10 grams 3 x/day mycelium grown on grain or soy; 3-12 grams/day watery extract; 1-2 ml, 3 x daily ethanolic extract

•10 •9/3/2014

Cordyceps Traditional Oyster Mushroom Indications, Dose Pleurotus ostreatus

• Widely cultivated, • PROPERTIES sweet, warm 3rd most commonly • CHANNELS ENTERED Lung, Kidney available in markets • KEY CHARACTERISTICS gently tonifies the Kidney yang, • Grows on alder, augments the essence, tonifies the Lungs, settles coughs and tanbark oak; other wheezing, stops sweating hardwoods • DOSAGE 3-9g • Cholesterol- • CAUTIONS & CONTRAINDICATIONS Use with caution lowering properties in those with exterior conditions.

Pleurotus ostreatus Pleurotus ostreatus Biological Effects Clinical Indications

• Antihyperlipidemic • Clinical indications – Total cholesterol fell up to 33%, also LDL, VLDL, – Hypercholesterolemia (2 g/kg/day = 4 ounces/day) triacylglycerol, but not HDL (5% of diet in rats, rabbits) – Reduction of colon cancer risk, other cancers (with – Mevinolin, crude form of Lovastatin found in Pleurotus significant amount in diet--up to 15%, 5% showed few cultures (23 mg/100 mL) benefits) – Mushroom extract inhibits HMG CoA reductase • Antitumor Dose: mushroom powder: up to 120 grams (4 ounces)/day – Inhibits colon cancer in rats (15% of diet) in diet – Natural killer cell (NK) and lymphokine-activated killer (LAK) cells attacked tumor cells Side Effects, Contraindications: rarely, contact dermatitis

Schizophyllum commune Schizophyllum commune Split-Gill Biological Effects

• Antitumor • Restores natural killer cell activity to normal in Note split- mice with cancer ”gills” • Increases resistance against bacterial infection • Good protective effects against damage of the bone marrow against chemotherapy

• Tumor-reducing extract called schizophyllan is produced in Japan

•11 •9/3/2014

Schizophyllum commune Schizophyllum commune Clinical Trials Clinical Indications

• Survival rates significantly increased in studies of • Clinical indications 367,323 patients with gastric cancers when given – Gastric cancer (with chemotherapy and radiation) with chemo and/or radiation – Cervical cancer • Better 5-year survival rates in women with stage II – Oral carcinoma cervical cancer when given with radiation therapy, – Hepatitis B (theoretical), chronic fatigue syndrome along with stronger T-helper cell activity and – Infectious diseases improvements in other immune functions • In traditional Chinese medicine: • Open trial showing benefits in 11 patients with chronic fatigue syndrome – leucorrhea • Dose: 9-16 g in decoction, 3X/day

Armillaria mellea Armillaria mellea

• Clinical indications • Clinical trials • Honey mushroom – Hypercholesterolemia • Open trials: reduces attacks live – Anticonvulsant hypertension, benefits hardwoods, – Leg pain, epilepsy neurasthenia – Improve night vision including fruit trees • In vitro, in vivo studies – Increases blood flow to – Antibacterial, antifungal • Massive mycelial brain: dizziness, insomnia, networks cover neurasthenia, tinnitis – Antitumor effects • Dose: fruit body, 30 gr; many acres, one of – Decreases heart rate, tincture, 1-3 ml (b.i.d.) reduces peripheral Earth’s oldest living • Contraindications, Side arterial resistance, organisms Effects: don’t exceed recommended dose; diarrhea increases coronary oxygen efficiency

Fomes officinalis Fomes officinalis Quinine Conk • “Panacea • Clinical indications mushroom of the – Panacea according to • Clinical trials ancient Greeks Disocorides, Gerard • none • Major ingredient – Hypercholesterolemia of Mithridate, – Toxemia • In vitro, in vivo studies Warburg tincture – Constipation – Antitumor • “Quinine conk” – Antimalarial – CNS depression in in the early U.S.; – Brochial asthma high doses shot from trees – Night sweats with rifles for • Dose sale as quinine – 3-5 grams/day substitute decoction, 1-2 ml tinc.

•12 •9/3/2014

Inonotus obliquus Inonotus obliquus Chaga • Sterile conk • Studies show that grows on antitumor, anticancer yellow birch in effect ne U.S., ne Europe, Russia • Some clinical trials • May protect from Russia show tree after injury benefit in cancers • Absorbs • Common on yellow betulinic acid, birch in n Vermont, NY an antitumor compound Renowned cancer remedy in Russia

Ustilago maydis Auricularia auricula Corn Smut, Cuitlacoche Wood Ear

• Grows on corn kernels • Auricularia polytricha is used interchangeably • Delicacy in Mexican according to the Pen T’sao cooking • Used in Chinese cooking • Similar, but much milder action than ergot • In Europe, wood ear was boiled to treat throat • Contains uterine-contracting inflammation, eye irritation alkaloids • Biological effects: • Official in the USP antitumor, antiulcer effect, • Uses: postpartum bleeding, hypocholesterolemic, partus preparator antidiabetic, beta-cell Wood ear in the Amazon • Dose: 1-3 ml protective effect, antioxidant, antiageing

Auricularia auricula Boletus edulis Wood Ear King Bolete, Porcini • Uses in TCM: • Delicious mushroom on all continents – Moves blood, stops pain • Cancer-protective effect – Increases physical, mental energy – Slows excessive uterine bleeding – Eases abdominal pain – Low back pain – Debility after childbirth – Muscle spasms – Poor circulation – Clears phlegm, strenghens lungs

•13 •9/3/2014

Fomitopsis pinicola Amanita muscaria Red-Belted Polypore Fly Agaric • Common polypore on conifers, • Mother tincture used homeopathically for epilepsy especially Douglas fir • Paste applied to wounds • Kings: intermittent fevers, chronic diarrhea, neuralgia, nervous headaches, excessive urination, jaundice, fevers of tuberculosis

Death Cap Amanita phalloides Silybum marianum

• Contains 2 kinds of liver toxins; destroys liver cells; possibly deadly • Milk thistle has reduced death rate to 0 in Europe • CDC has refused to use it in the U.S.

Lenzites betulinus Piptoporus betulinus Gilled Polypore Birch Polypore • Used in China in • Grows in “Tendon-Easing Pills” eastern hardwood forests on birch • Some immuno- modulating effects shown

•14 •9/3/2014

Pycnoporus cinnabarinus Cinnabar Polypore • Used in the Amazon and se Asia in medicinal teas

•15