Klinické štúdie - clinical guide
1. Chaga – Kabanoanatake – Bai Hua Rong
Japanese name - Kabanoanatake
Chinese name - Bai Hua Rong / Hua Jie Kong Jun
English name - Chaga
I.obliquus grows widely in the forest of Eastern Europe and Russia on several trees, including birch, alder and spruce, where it appears as a sterile growth or conk on the trunk of the tree. The fruiting body is reported to be found growing nearby but is extremely rare in nature.
Traditionally only I.obliquus growing on birch trees was used as a tea in the treatment of cancers including inoperable breast cancer, hip, gastric, parotid, pulmonary, stomach, skin, rectal and Hodgkin lymphoma and I.obliquus is recorded as a miraculous cure for cancer in Solzhenitsyn´s semi-autobiographical 1967 novel, the ´Cancer Ward´.
The wisdom of using birch grown I.obliquus is supported by the finding that some of its key components are the triterpenoids betulin and betulinic acid, which occur naturally in a numebr of plants but primarily in the bark of the white birch (Betula pubescens - seen as the tree of life and fertility in many Eastern European and Siberian myths) from which it gets its name. Although it has been assumed that I.obliquus derives betulinic acid exclusively from the bark of host birch trees a recent study reported a small amount of betulin (0.12%) in I.obliquus mycelial biomass grown on rice indicating that some may also be generated by the mushroom itself.
Betulinic acid has been shown to induce mitochondrial apoptosis in different cancer cell lines and inhibit the enzyme topoisomerase, which is essential for the unwinding and winding of the DNA strands in cell replication. In addition it possesses anti-retroviral, anti-parasitic and anti-inflammatory properties. It is currently being developed as an anti-cancer agent through the Rapid Access to Intervention Development program of the US National Cancer Institute and is also a major contributor to the anti-cancer action of mistletoe.
Other important components of I.obliquus include pollysaccharides and sterols. Its high phenolic content gives it exceptional antioxidant properties and a melanin complex has also been identified as having significant antioxidant and genoprotective properties.
CANCER - Widely used in Poland and Russia as a folk remedy against cancer, I.obliquus is now attracting increasing interest among practitioners with its combination of immune supporting polysaccharides and triterpenoid components with direct anti-cancer activity, especially betulinic acid derivatives.
In vitro studies on betulinic acid have shown it to be highly effective against a wide variety of cancer cells: human melanoma, neuroectodermal (neuroblastoma, medulloblastoma, Ewing´s sarcoma) and malignant brain tumours, ovarian cancer human leukaemia HL-60 cells and malignant head and neck squamos cell cancers, including those derived from therapy-resistant and refractory tumours. However, it was found to have no effect on epithelial tumours, such as breast cancer, colon cancer, small cell lung cancer and renal cell cancer as well as T-cell leukaemia cells. Its anti-tumour activity has been related to its direct effects on mitochondria and induction o apoptosis, irrespective of cells p53 status.
Both betulinic acid and polysaccharides from I.obliquus have significant in vitro activity against brain cancer cells with one study showing that betulinic acid exerted cytotoxic activity against primary tumour cells cultured from patients 4 of 4 medulloblastoma-tumour samples tested and in 20 of 24 glioblastoma-tumour samples. It also shows great promise in combination with radiotherapy, exhibiting a strictly additive mode of growth inhibition in combination with radiation in human melanoma cells in one study and acting as a radiosensitizer in head and neck squamos cell cancers in another.
In vivo studies confirm its anti-cancer action as well as a complete absence of systemic toxicity in rodents.
DIGESTIVE DISORDERS - Melano-glucan complexes have wide antimicrobial activity and I.obliquus has traditionally been used as an internal cleanser with Befungin, an alcohol extract of I.obliquus, licensed in Russia for the treatment of stomach and intestinal disorders.
PSORIASIS - Several anecdotal reports indicate benefit of I.obliquus for psoriasis and this is supported by a Russian study on 50 psoriasis patients, which reported a 76% cure rate, with improvement in a further 16% of cases. The same study reported that it typically took 9-12 weeks for improvement to become apparent.
ANTI-VIRAL - I.obliquus has traditionally been used to treat a number of viral conditions and aqueous extracts of I.obliquus prevented Herpes simplex virus entry through inhibiton of viral-induced membrane fusion with a 50% inhibitory concentration of 3.82 µg/ml. Betulinic acid analogs have also been shown to disrupt assembly and budding of the HIV-1 virus and viral fusion to the cell membrane.
Main Therapeutic Application - Cancer, anti-viral, antioxidant.
Key Component - Pollysaccharides, betulin and betulinic acid derivatives.
Dose - It is reported that only aqueous extracts prepared by boiling, as done traditionally, show anti-tumour activity. However the level of triterpenes in pure aqueous extracts is low and many practitioners prefer to combine aqueous and ethanolic extracts. Average dosage for aqueous extractx as powder is 1-3g/day.
Safety - I.obliquus contains high oxalate concentrations and there is one report of a 72-year-old Japanese woman diagnosed with liver cancer who developed oxalate nephropathy after consuming 4-5 teaspoons a day of I.obliquus powder for 6 months.
2. Cordyceps: Caterpillar Fungus – Tochukas – Dong Chong Xia Cao
Cordyceps species are unique among the medicinal mushrooms in growing on an insect host rather than a plant host. To date over 700 species of cordyceps have been identified worldwide, in most cases growing parasitically on their insect hosts. However, it has also been suggested that in some cases a symbiotic relationship exists whereby the insect host derives a selective advantage from the fungal anamorph (the asexual form of the fungus), especially in marginal environments where energy efficiency is at a premium, such as the high Tibetan plateau above 3.000m where the main species used traditionally, Ophiocordyceps sinensis, occurs naturally (although previously part of the Cordyceps genus, molecular phylogenetic analysis has now led to its being placed in a separate genus, the Ophiocordycipitacae).
Although traditionally harvested cordyceps is still available, the vast majority of cordyceps on the market today is cultivated on non-insect, grain-based subtrates leading to improved quality control and affordability. Despite the commercially cultivated cordyceps being grown on a different substrate from wild collected cordyceps, HPLC analysis shows identical chemical profiles and the two are seen to be interchangeable clinically.
As well as polysaccharides and lipids, cordyceps species contain a large number of nucleoside analogues, prominent among which is cordycepin, 3-deoxyadenosine, whoch is found in a high levels in Cordyceps militaris and which differs from adenosine in the absence of oxygen at the 3 position of its ribose part. Because of its close similarity to adenosine some enzymes cannot distinguish between the two and it is able to participate in certain biochemical reactions, including RNA/DNA synthesis, where its incorporation leads to the termination of the RNA/DNA molecule, there being no oxygen to bond with the next nucleotide.
This ability to interrupt RNA/DNA synthesis has led to the use of such nucleoside analogues, termed reverse transcriptase inhibitors, in the treatment of viral infections including HIV and hepatitis as well as cancer, under pharmaceutical names including AZT (Retrovir), Videx and Epivir. In normal healthy cells such reverse transcriptase inhibitors are out-competed by the corresponding nucleoside but in rapidly dividing cancer cells and virally infected cells they are able to exert effective inhibition of replication.
Adenosine in the form of adenosine monophosphate and adenosine triphosphate also plays a central role in energy metabolism and cyclic nucleotides including cAMP play an important role in signal transduction and regulation of hormone production, actions which correlate well with the observed activity of cordyceps in these areas.
As well as O.sinensis and Cordyceps militaris, a large number of trials have been carried out using a fungal strain isolated from wild O.sinensis specimens by China´s Academy of Sciences and selected for ease of cultivation by large-scale liquid fermentation technology. Termed Cs-4, this is currently identified as Paecilomyces haepiali and continues to be one of the main cordyceps related species used in China.
One in vitro study, however, showed Cs-4 to have immune-suppressive activity and the immune-suppressant drug Cyclosporin A has been shown to be present in other fungal strains isolated from wild O.sinensis specimens.
ANTI-AGEING - O.sinensis has traditionally been used as a supplement for the elderly and those recovering from long illness. Studies with Cs4 in healthy elderly subjects showed significant increases in oxygen uptake, aerobic capacity and resistance to fatigue.
Experimental evidence based on polysaccharide extracts indicates that O.sinensis is also able to improve brain function and antioxidative enzyme activity (superoxide dismutase, glutathione peroxidase and catalase), which, together with its beneficial effect on cardiovascular function, makes it an excellent supplement for the elderly.
ATHLETIC PERFORMANCE - The use of O.sinensis, together with other supplements, by the record breaking Chinese athletes of the early 1990s has attracted considerable interest in its potential to enhance athletic performance.
A 1996 study on long distance runners reported a significant improvement in 71% of participants and O.sinensis and C.militaris as well as the cordyceps anamorphs Cs-4 and Cs-HK1, have been shown to increase endurance in animal models. Studies on sedentary humans also show a significant increase in energy output and oxygen capacity. However, three studies failed to demonstrate any effect on performance in competitive cyclists or other professional athletes and it has been suggested that this may be because such athletes are already operating at or close to their maximum aerobic capacity.
SEXUAL FUNCTION - O.sinensis produces clear benefits for male sexual hypofunction when taken over a period of time. Aanecdotal evidence and reports from China also indicate possible benefits for female libido.
Based on animal studies O.sinensis and C.militaris have a clear effect on increasing levels of male sex hormones, improving testes morphology, sperm quantity and quality. In vitro research indicates that cordyceps affects the signal transduction pathway of steroidogenesis after the formation of cAMP.
FERTILITY - O.sinensis is increasingly being used by leading specialists in the field of infertility and clinical evidence suggests that cordyceps has a beneficial impact on female fertility and the success of IVF. In part this may be due to its ability to stimulate 17ß-estradiol (oestrogen) production, through increased StAR (steroidogenic acute regulatory protein) and aromatase expression. In common with other mushrooms, cordyceps´ ability to regulate immune function and in particular NK cell activity may also play a part.
The ability of O.sinensis to increase oestrogen production also has potential for the management of postmenopausal osteoporosis.
DIABETES - Experimental evidence indicates taht O.sinensis is able to:
In one randomized trial 95% of patients treated with 3g/day O.sinensis mycelial biomasssaw improvements in their blood sugar profile compared with 54% treated by other methods. In addition it has been reported that consumption of 4.5g/day O.sinensis mycelial biomass by patients with alcohol induced diabetes also produced a reduced desire for alcohol.
Recent evidence indicates that cordycepin and related nucleoside derivatives play an active role in the anti-diabetic action of O.sinensis and that C.militaris, which has high levels of cordycepin, also has significant hypoglycaemic activity.
HEPATOPROTECTIVE - Multiply studies has shownthe ability of both O.sinensis and C.militaris to inhibit hepatic fibrosis and help restore liver function. One clinical study using 3g/day O.sinensis mycelial biomass to treat alcohol-induced liver steatosis in 14 patients showed reductions of 70% in AST levels, 63% in ALT levels and 64% in GGT levels over a 90 day period.
RENAL HEALTH - O.sinensis has traditionally been considered to support the kidneys and 3.5g/day has been shown to both improve kidney function in patients with chronic renal failure and speed recovery in patients with gentamycin-induced kidney damage.
RESPIRATORY DISEASE - Traditionally O.sinensis has been used to treat respiratory ailments and is reported to be beneficial for asthma and COPD.
ANTI-VIRAL - As mentioned above, the nucleoside analogues present in cordyceps species are able to inhibit viral replication. At the same time the polysaccharides in cordyceps modulate the immune response to viral infections. This combination of enhanced immune response and interrupted viral replication makes cordyceps, especially C.militaris, one of the most effective mushrooms for tackling chronic viral infections.
CANCER - Because of its combination of immune-modulating polysaccharides and nucleoside derivatives, many practitioners consider Cordyceps to be one of the most useful mushrooms for helping improve treatment outcomes in cancer, with cordycepin reported to induce apoptosis (cancer cell death) in multiply cancer cell lines, including: oral, colorectal, bladder, leukaemia, melanoma, multiple myeloma, breast and prostate.
Main Therapeutic Applications - Fertility and sexual function, energy, diabetes, lung function, kidney support, liver disorders.
Key Component - Nucleoside derivatives.
Dose - Cordyceps´ unique properties are principally those of its nucleoside derivatives and as these are largely excreted (research on C.militaris shows that 98% of cordycepin is secreted into the growth medium) mycelial biomass products offer the natural dosage format for cordyceps. 2-3g/day mycelial biomass is used in most cases while higher levels have been reported to give good results in a range of cancers.
Some practitioners prefer to use C.militaris for cancer and viral infections due to its higher cordycepin levels.
Caution - Hormone dependent cancers (prostate and breast) due to increased levels of oestrogen and testosterone.
Although Cs-4 shows benefits for exercise and endurance, possible immune suppressions mitigates against its use in immune deficient conditions.
3. Coriolus: Turkey Tail - Kawaratake - Yun Zhi
T.versicolor is the most extensively researched of all medicinal mushrooms with large scale clinical trials on the extracts PSK (´Krestin´) and PSP showing impressive results in a variety of cancers including gastric, oesophageal, lung, breast and colorectal.
PSK and PSP are both polysaccharide-protein complexes that are soluble in water but insoluble in ethanol. PSK contains 34-35% polysaccharide (~92% glucan) and 28-35% protein.
PSK has been shown to boost immune cell production, ameliorate chemotherapy and radiotherapy side effects, enhance immune status and tumour infiltration by dendritic and cytotoxic cells and significantly extendsurvival in cancers of the stomach, colon-rectum, oesophagus, nasopharynx, uterus and lung (non-small cell types), and in an HLA B40-positive breast cancer subset in combination with conventional treatment. In addition to its immune related effects, PSK has shown an ability to enhance superoxide dismutase and glutathione peroxidase activity.
PSP has been shown to significantly enhance immune status in 70-97% of patients with cancers of the stomach, oesophagus, lung, ovary and cervix.
Although most clinical trials have been conducted with the above proteoglycan extracts, there is also evidence of immunomodulatory action for T.versicolor mycelial biomass, with improvements of immune status in patients with chronic fatigue syndrome and enhanced clearance of low grade squamous intraepithelial lesions (LSIL) from the cervix.
CANCER - The use of T.versicolor extracts in cancer treatment is supported by a significant number of clinical trials.
STOMACH CANCER - Multiple clinical trials of PSK given alongside surgery and chemotherapy at 3-6g/day significantly extended survival times in stomach cancer at all stages. Even in patients with advanced stomach cancer with metastasis PSK doubled 2-year and 5-year survival and extended 15-year survival.
COLORECTAL - In different clinical trials PSK extended 5-year and 8-year survival after surgery and chemotherapy and after surgery, chemotherapy and radiotherapy.
LUNG CANCER (NSCLC) STAGES I-III - PSK extended 5-year survival 2-4x for all cancer stages with stage III cancer patients taking PSK having a better prognosis than stage II patients without PSK.
OESOPHAGEAL- PSK extended 5-year survival after surgery, radiotherapy and chemotherapy while in double-blind trials PSP significantly extended 5-year survival in oesophageal cancer as well as improving quality of life, providing substantial pain relief and enhancing immune status in 70-97% of patients with cancers of the stomach, oesophagus, lung, ovary and cervix at a dose of 3g/day.
NASOPHARYNGEAL- PSK extended 5-year survival after radiotherapy and chemotherapy (28% vs, 15%).
BREAST CANCER- Evidence from clinical trials (given alongside chemotherapy) is mixed. In one trial PSK was shown to extend survival in patients with oestrogen receptor negative, non-metastasised, stage II cancer but no benefit was shown in another. In a third trial significant benefit was seen in patients positive for HLA B40 with 100% survival after 10 years.
CERVICAL/UTERINE CANCER- In combination with radiotherapy PSK (3-6g/day) given to patients with stage III uterine and cervical cancer enhanced survival and increased sensitivity of the cancers to radiotherapy. In another trial cervical cancer patients given the same dose together with radiotherapy showed clearance of cancer cells in 36% of patients versus 11% of controls and improved 5-year survival from 48% to 79%. In a recent study using T.versicolor biomass, supplementation with 3g/day produced a 72.5% regression rate in LSIL lesions, compared to 47.5% without supplementation, and also increased the clearance of high risk HPV strains from 8.5% to 91.5%.
HIV- In several in vitro experiments PSK was found to exhibit anti-HIV activity through multiple routes:
Use of T.versicolor supplementation (3.0g/day T.versicolor biomass) has been reported to improve HIV patients´ immune status and produce improvement in HIV related Kaposi´s sarcoma.
HERPES- Clinically T.versicolor supplementation is seen to reduce the frequency of Herpes simplex virus (HSV) outbreaks and it has also been shown to inactivate HSV in a dose-dependent manner.
CHRONIC FATIGUE SYNDROME(ME) - T.versicolor biomass has shown promise in the treatment of Chronic Fatigue Syndrome with immune system activation and increased NK cell activity reported in patients at 1.5g/day (3g/day for the first 2 weeks) over a 2 month period.
- T.versicolor polysaccharides extracts
demonstrate hepatoprotective properties.
Main Therapeutic Application -
Key Component - Pollysaccharides.
Dose - Commercial polysaccharide extracts are commonly prescribed at 3g/day and for long term use may be given in cycles of two weeks on, two weeks off. Dosage for crude polysaccharide extracts is typically 3-6g/day for cancer and 1-2g/day for immune support. For chronic immune deficient conditions the biomass also shows promise at 3g/day.
4. Honey Mushroom – Naratake – Mi Huan Jun
A.mellea is a common fungus that produces edible fruiting bodies with a distinctive golden colour. A single example can grow to cover a vast area and it is reported that the largest living organism in the world is a related species of honey fungus covering on area of 2400 acres in Oregon, USA, with estimates of its age ranging from 1900 to 8650 years.
Although responsible for the death of many trees and garden shrubs, A.mellea is essential for the growth of other plants, including the important Chinese herb Gastrodia elata (Tian Ma), which is used to treat conditions including vertigo, dizziness, headache, stroke and convulsions and whose medical properties A.mellea mirrors. Indeed A.mellea is considered the more potent of the two with an effective dosage half that of Tian Ma.
Early reports indicated that A.mellea and G.ellata shared the same active components but it is now known that they differ in their active metabolites.
As well as being essential for the growth of G.ellata, it has been shown that Armillaria species are involved in sclerotium formation in Polyporus umbellatus.
A.mellea mycelium contains high levels of polysaccharides with anti-ageing, immune-modulating and anti-vertigo activity. In addition, nucleoside analogues play a role in some of A.mellea´s functions and a number of indole compounds have been isolated including tryptamine, L-tryptophan and serotonin, with A.mellea fruiting bodies containing 2.207mg serotonin per 100g dry weight.
Several antibiotics, primarily sesquiterpene aryl esters, have been isolated from A.mellea and show strong action against gram-positive bacteria (Staphylococcus, Streptococcus, Enterococcus etc.), as well as yeasts and other fungi.
NEUROLOGICAL- Tablets composed of A.mellea mycelium are prescribed in China for treating of variety of neurological conditions including Meniere´s Syndrome, vertigo, headache, insomnia, epilepsy, neurasthenia and hypertension.
A.mellea fermentation extract showed anti-convulsant properties, raising the seizure treshold in PTZ-induced seizures in mice, while an adenosine derivative from the mycelium abolished neurogenic twitch responses induced by electrical field stimulation with both pre- and post-synapse depression, as well as being found to be 1.000 times stronger than adenosine in its cerebral protecting activity. In addition A.mellea polysaccharide extract was shown to benefit vertigo induced by machinery rotation.
Main Therapeutic Application - Meniere´s syndrome, vertigo, epilepsy.
Key Components - Polysaccharides, nucleoside derivatives and sesquiterpene aryl esters.
Dose - Mycelial tablets are used in China 3-4g/day.
5. Lion's Mane - Yamabushitake - Hou Tou Gu
This delicious mushroom has been referred to as ´Nature´s Nutrient for the Neurons´ on account of its ability to stimulate the production of nerve growth factor (NGF).
NGF plays an essential role in the differentiation and survival of several cell populations in the central and peripheral nervous system and lower than normal levels of NGF have been linked to early stages of both Alzheimer´s disease and dementia.
Although therapeutic interest has largela focussed on its importance for neurological function, NGF plays a much wider role in maintaining homoeostasis in the body. It is known to have insulinotropic, angiogenic, and antioxidant properties and reduced plasma levels of NGF have been associated with cardiovascular diseases and metabolic syndromes, including type 2 diabetes. It has been shown to accelerate wound healing and there is evidence that it could be useful in the treatment of skin and corneal ulcers. Animal studies have shown NGF to have a profound effect on airway inflammation and asthma-related symptoms with increased NGF levels observed in bronchoalveolar lavage fluid and serum from patients with asthma.
NGF also has a dynamic relationship with the immune system. Generation of NGF is increased after brain injury, in part due to cytokines produced by immune cells. At the same time immune cells express receptors for NGF, which is involved in immune modulation.
Two families of compounds from H.erinaceus have been identified as being active in the stimuýlation of NGF production: the aromatic hericenones (isolated from the fruiting body) and the diterpenoid erinacines (isolated from the mycelium). Critically these molecules are small enough to pass through the blood-brain barrier. There is also evidence that they can increase myelination.
In China the mycelium is used to make H.erinaceus pills to treat gastric and duodenal ulcers, chronic gastritis, gastric and oesophageal cancer.
DEMENTIA- In controlled studies H.erinaceus supplementation showed beneficial effects in patients with mild dementia. In one study six out of seven patients showed improvements in functional capacity (understanding, communication, memory etc.) whle all seven showed improved Functional Independence Scores (eating, dressing, walking etc.), after consuming 5g H.erinaceus fruitnig body daily in soup for six months.
In another study, 30 patients aged 50-80 with mild dementia were randomised into treatment and control groups. H.erinaceus was given as tablets at 3g/day for 16 weeks and produced significant increases in cognitive function in the treatment group. However, four weeks after the conclusion of the trial, cognitive function scores decreased indicating a need for continued supplementation.
MS- H.erinaceus fruiting body extract has been shown to improve the myelination process in mature myelinating fibres with possible benefits for MS patients. NGF has also been shown to have a protective effect on axons and myelin by suppresing the immune-mediated inflammatory processes responsible for chronic brain destruction in neurodegenerative disorders such as MS by switching the immune response to an anti-iflammatory, suppressive mode in a brain-specific environment.
NEUROPATHY- NGF plays a role in pain sensitivity and low NGF levels have been linked to sensory neuropathy in both in vivo and in vitro studies. Enhanced NGF production has been shown to protect sensory function in diabetic rats and NGF reduction has been shown to cause cardiac sensory neuropathy.
Clinical studies with recombinant human NGF indicate benefit in patients with diabetic polyneuropathy and NGF has also been reported to reduce pain in patients with HIV associated sensory neuropathy. However, ability to promote regeneration of sensory neurons has yet to be demonstrated.
NERVE DAMAGE- Rats given aqueous extract of H.erinaceus fruitnig bodies showed faster recovery from nerve injury, suggesting potential for application of H.erinaceus in the early stages of nerve regeneration.
ANXIETY/DEPRESSION- One study reports reducltion in anxiety and depression from consumption of 2g/day (taken in cookies) and patients often report increased feelings of wellbeing when taking H.erinaceus, possibly due to the kappa opiod receptor gonist activity of the erinacines.
MENOPAUSAL SYNDROME- Many patients report reduction in symptoms related to menopause and perimenopause, including sleep disturbance, anxiety and hot flushes (hot flashes) from consumption of H.erinaceus 3-5g/day d.w. although this is a yet unsupported by clinical research.
MRSA - Extracts of both fruitnig body and mycelium exhibit anti-MRSA activity with erinacines identified as active compounds. In clinical tests in Japan MRSA is reported to have been cleared in a number of patients whose diet was supplemented with H.erinaceus.
GASTRIC ULCERS - One of the traditional indications for H.erinaceus, it appears likely that the antibacterial action of the rinacines and hericenones contribute to its benefit in this regard, with Helicobacter pylori now known to be a major cause of gastric ulcers and chronic gastritis.
A rat study on the effects of H.erinaceus aqueous extract on alcohol-induced ulcers showed a significant reductionof the ulcer area, as well as protection against gastric mucosa injury, while an in vitro study found that H.erinaceus extract was active against nine clinical strains of H.pylori with a 0.02% concentration having a 50% bactericidal activity.
Main Therapeutic Application - Dementia, Alzheimer´s disease, MS, nerve damage, menopausal syndrome.
Key Component - Hericenones and erinacines.
Dose - Clinical trials support the use of dried fruiting body at a dose of 3-5g/day for increasing NGF production while animal studies on the use of H.erinaceus for gastric ulcers produced the best results with a daily intake of 500mg/kg, which equates to the dosage prescribed in the Chinese Pharmacopoeia of 25-50g/day. It is likely that similar doses would be required in cases of MRSA.
High in vitro NGF promoting activity of mycelial extracts and the fermentation broth also indicates potential for the use of mycelial biomass products.
Caution - Asthma and other allergic conditions. Erinacine E is a potent agonist of the kappa opioid receptor with potential hallucinogenic properties.
6. Maitake: Hen of the Woods – Maitake – Hui Shu Hua
A popular gourmet mushroom, G.frondosa is also a highly regarded clinically, especially in cancer therapy. As with other major anti-cancer mushrooms such as Lentinula edodes (Shiitake) and Trametes versicolor (Coriolus), polysaccharides have been shown to be the major active components of G.frondosa and several beta-glucan, heteropolysaccharide and proteoglycan fractions have been isolated with potent immunomodulatory action, including D-fraction and MD-fraction.
Most of the clinicall research has been carried out by one group of researchers in Japan, initially using D-fraction together with powdered fruiting body, later switching to the more bioactive MD-fraction, again in combination with powdered whole fruiting body.
-A 1997 paper by Nanba reported benefits from D-fraction taken
together with whole fruiting body in a range of stage III-IV cancers with
G.forondosa increasing the benefit of chemotherapy by an additional 12-28%.
The paper further reports synergistic benefits from combining D-fraction and
Mytomicin C (MMC) in an animal tumour model with D-fraction (1mg/day) showing
superior tumour inhibition to MMC (0.5mg/day) on its own.
A subsequent paper by Nanba et al reported impressive results for MD-fraction and whole G.frondosa fruiting body powder in cancer patients who had discontinued chemotherapy because of side effects with improvement in 7 of 12 liver cancer patients, 11 of 16 breast cancer and 5 of 8 lung cancer patients, together with increases in IL-2 (a major Th1 cytokine) and CD4+.
Further studies confirmed alleviation of side effects from chemotherapy, including loss of appetite, vomiting, nausea, hair loss and leukopaenia, as well as synergy between D-fraction and vitamin C.
DIABETES- Various animal studies indicate benefit from G.frondosa in diabetes models but at high doses, in one case giving 1g/day G.frondosa powder to genetically diabetic mice and in another a purified alpha-glucan at a dose of 150-450mg/kg.
In small scale clinical studies
G.frondosa polysaccharide extract (dose unknown) was reported to
control blood sugar levels in one patient and produce a 30% reduction in blood
sugar levels in 4 other patients while inclusion of G.frondosa
beta-glucans (150mg/day) in yoghurt produced significant improvement in blood
glucose levels in 20 type II diabetes patients.
SYNDROME (PCOS) - In the majority of cases, PCOS
is associated with some level of insulin resistance and G.frondosa
polysaccharide extracts also show promise as agents for helping address this
In addition, all 3 women who expressed an interest in becoming pregnant were able to do so.
CHOLESTEROL- Inclusion of G.frondosa in the diet of experimental animals at 5-20% of feed produces reductions in cholesterol consistent with the results seen in other mushrooms.
HYPERTENSION - A
number of studies report short-lived hypotensive action for G.frondosa
included in the diet of hypertensive animals (typically 5% of feed).
Main Therapeutic Application - Cancer, PCOS.
Key Component - Polysaccharides.
Dose - The optimum dose of D-fraction/MD-fraction in animal studies is reported to be 1mg/kg i.p. with human trials using D-fraction/MD-fraction at oral doses of 35-150mg/day in combination with 4-6g/day G.frondosa fruiting body.
7. Mesima: Meshimakobu - Song Gen
P.linteus is a basiidiomycete fungus, popular in China, Korea and Japan and reported to work as a ´miracle medicine´, prolonging longevity. Identified by Ikekawa as having the highest anti-tumour activity of the Hymenomycetes (a fungal grouping containing the major medicinal mushrooms), and by Stamets as having the greatest macrophage activation of 7 species surveyed, it has been heavily researched in the last decade, especially in Korea, showing broad immunostimulant activity, strong anti-cancer properties and the ability to enhance the efficacy of existing chemotherapeutic drugs.
Uniquely among the medicinal mushrooms, the Chinese pharmacopoeia describes the energy of P.linteus as Cold and ascribes to it an extensive range of indications, including: cancer, diabetes, HIV, angina, leucorrhoea, diarrhoea and accelerated wound healing.
Research has focused on P.linteus´ polysaccharide and proteoglycan components although it also contains a number of flavonoid-like polyphenol pigments with antioxidant, anti-inflammatory, cytotoxic and anti-viral effects.
Interest in the potential of P.linteus in cancer therapy has been
stimulated by recent reports of remarkable effects in a number of cancer
patients taking it. One case reporteddramatic remission in a hormone refractory
prostate cancer with rapidly progressive bone metastasis, while in a second a 65
year old man with a large hepatocellular cancer and metastasis in the skull,
sternum and ribs, who declined all treatment except radiation for the painful
frontal bone mass in favour of P.linteus, experienced spontaneous
regression of the tumours. In a third case spontaneous regression of
hepatocellular cancer with multiple lung metastasis was linked to consumption of
P.linteus mycelium (no conventional therapy undertaken).
In vitro studies show that low levels of P.linteus polysaccharides induce cell cycle arrest in lung cancer cells and exhibit synergistic action with chemotherapeutic drugs such as doxorubicin, inducing apoptosis at a sub-therapeutic dose in prostate and lung cancer cells, hormone sensitive and, to a lesser degree, refractory prostate cancer cells. Modes of action identified include inhibition of Akt signalling and caspace induction.
In vitro studies also show significant inhibition of bladder cancer cell growth with enhanced cytotoxic activity in combination with vitamin C.
In vivo studies show significantly prolonged survival, reduced tumour growth and reduced frequency of lung metastasis in mice transplanted with melanoma cells after administration of polysaccharide extract.
RHEUMATOID ARTHRITIS - In a murine rheumatoid arthritis model polysaccharide extract from P.linteus fruiting bodies reduced expression of pro-inflammatory Th2 cytokines (such as TNF-α and IFN-γ) and increased expression of anti-inflammatory Th1 cytokines, including IL-10 and TGF-β, resulting in the subsidence of the autoimmune response in the joints of the mice. Similar results were seen with polysaccharides from the related species Phellinus rimosus.
P.linteus polysaccharides have also been shown to reduce expression TNF-α and major histocompatibility complex II expression in lipopolysaccharide induced septic shock, supporting their use as anti-inflammatory agents.
ALLERGIES - Several studies show strong effect of P.linteus polysaccharides in suppresing production of Th2 cytokines and promoting secretion of Th1 cytokines, thereby addressing the immune imbalance involved in allergic responses. At the same time it is reported that aqueous extract of P.linteus fruiting body prevented histamine release in response to allergenic stimuli and inhibited mast cell mediated anaphylaxis-like reactions.
Other atopic conditions have also shown benefit from P.linteus in animal models including asthma and dermatitis.
INFERTILITY - P.linteus shows considerable promise in cases where infertility is associated with elevated cytokine and NK cell levels, with 23 of 26 women in one study showing improvement in immune parameters from supplementation with mycelial biomass at 3g/day.
Therapeutic Application - Cancer, rheumatoid arthritis, allergies.
Key Component - Polysaccharides.
Dose - The Chinese Pharmacopoeia prescribes at daily dose of 10-30g for the dried mushroom, while for polysaccharide extract 2-3g/day is usual.
8. Oyster mushroom
One of the princial culinary mushrooms, P.ostreatus fruitning bodies contain lovastatin in concentrations ranging from 0.7-2.8% dried weight depending on the strain.
P.ostreatus has also been commercialized as a source of polysaccharide extracts for immune support and shows promise for general health maintenance.
Related species including Pleurotus eryngii, Pleurotus tuber-regium and Pleurotus citronopileatus show similar immune-modulating and cholesterol lowering activity.
CHOLESTEROL CONTROL - Dried P.ostreatus fed to hamsters at 2% of a high fat diet for six months is reported to have lowered VLDL by 65-80% and total serum lipid levels by 40% and to totally negate increases in triglyceride and liver cholesterol levels associated with chronic alcohol intake. Multiple animal studies show P.ostreatus to produce improvements in blood lipid levels at 5% of diet. Intake of more than 5% was seen to supress appetite.
Bobek at al reported reductions in cholesterol in humans from intake of 15-20g/day and Khatun et al reported P.ostreatus to reduce cholesterol levels in diabetic patients. However, in a small clinical study on HIV patients with elevated non-HDL cholesterol (>160mg/dl) who where taking protease inhibitors no significant change was seen from supplementation with 15g/day freeye/dried P.ostreatus for 8 weeks (abnormalities in lipid metabolism are a common side effect of anti-retroviral treatment).
ANTI-AGEING - As well as having immunomodulatory, anti-cancer and hepatoprotective properties in common with those from other mushrooms, polysaccharides from P.ostreatus have been shown to increase activity of catalase, superoxid dismutase and glutathione peroxidase, as well as counter age-related reductions in levels of vitamins C and E.
Therapeutic Application - General health maintenance, especially in the elderly. Can be prescribed for cholesterol control, although Monascus purpureus products (Hong Qu Mi - Red Yeast Rice) usuallz give a more controlled dose of lovastatin.
Key Components - Lovastatin, polysaccharides.
Dose - 1-2g/day polysaccharide extract or 2-3g/day mycelial biomass for general health maintenance, 10-15g/day dried fruit body for cholesterol control.
Caution- Patients taking protease inhibitors such as ritonavir, indinavir etc., which have been shown to raise statin levels significantly through common use of the CYP3A4 enzym system.
9. Reishi - Ling Zhi
The most famus of all the medicinal mushrooms with annual sales of over US dollars 2billion, G.lucidum´s wide-ranging health benefits are due to its combination of high polysaccharide content (Stamets reports the fruiting body to contain 41% beta-glucan) and triterpenoid compounds. Over 130 of these have been identified, belonging primarily to two families: ganoderic and lucidenic acids with functions including: inhibiting histamine release, hepatoprotective, anti-hypertensive (ACE inhibiting), inhibiting cholesterol synthesis, anti-iflammatory, inducing apoptosis, inhibiting viral induction, antioxidant, anti-tumour, CNS sedation, antimicrobial, immune modulation.
Levels of triterpenes are particularly high in G.lucidum spores, typically >2.0% in shell-broken spore powder and >30% in the spore oil and recent studies report promise for the spores and spore oil as anti-cancer and neuroprotective agents.
G.lucidum shows exceptionally high tyrosinase inhibition with the highest activity in the aqueous extract. This has led to its inclusion in many commercial skin whitening products and has medical implications, especially in relation to Parkinson´s Disease.
A number of related species have also been investigated with polysaccharides and triterpenes from both Ganoderma tsugae and Ganoderma applanatum showing similar anti-tumour, anti-inflammatory, immune-modulatory and hepatoprotective activity to those from G.lucidum and Ganoderma japonicum showing neuroprotective properties.
CANCER - G.lucidum has a long history of traditional use in the treatment of cancer and is credited with many cases of spontaneous remission. As well as the immune modulating effect of its high polysaccharide content, its triterpenes show significant cytotoxic activity against different cancer cell lines, as well as inhibitory effects against Epstein-Barr virus, known to be associated with some cancers. In addition triterpenes from G.lucidum show inhibition of the nuclear transcription factor, NF-kappaB (NF-kB), which is overexpressed in various cancer cell lines, and also the AP-1 signalling pathway.
Inhibition of NF-kB is of particular importance in the activity of G.lucidum against breast and prostate cancers as iti is considered to play an essential role in the hormone independent growth and spread of these cancers. In addition G.lucidum triterpenes have been shown to block the androgen receptor on prostate cancer cells, supporting G.lucidum´s use in the treatment of prostate cancer.
Clinical studies with G.lucidum polysaccharide extract confirm its ability to enhance immune status in cancer patients with increases in NK cell activity and Th1 cytokine levels and decreases in Th2 cytokine levels in advanced lung cancer patients, and reduction in side effect when given alongside chemotherapy and radiotherapy.
In vitro and in vivo studies also indicate significant anti-tumour activity for the triterpene-rich G.lucidum spore powder and spore oil. A randomized controlled trial of 48 breast cancer patients reported reductions in fatigue, anxiety and depression in the treatment group (3g/day G.lucidum spore powder), together with improvements in immune parameters.
ALLERGIES - As well as immunomodulatory activity, G.lucidum demonstrates strong anti-inflammatory activity with suppression of tumour necrosis factr-alpha (TNF-alpha), interleukin-6 (IL-6), the iflammatory mediator nitric oxide (NO)and prostaglandin E2, mediated through inhibition of the NF-kB and AP-1 signaling pathways. This combination of immunomodulatory and anti-inflammatory activity contributes to its efficacy in the treatment of allergies and other iflammatory conditions.
G.lucidum is a component of FAHF-2, a Chinese herbal formula that has been reported to completely block anaphylactic reactions in a mouse model of peanut allergy.
LIVER DISEASE - The fruiting body of G.lucidum has long been a popular traditinal treatment for liver diseases and demonstrates wide hepatoprotective properties. It appears that at least part of its action in this regard may be through the ability of G.lucidum triterpenes to block platelet-derived growth factor beta receptor (PDGFbetaR), thus inhibiting the activation and proliferation of hepatic stellate cells, a key event in hepatic fibrosis.
G.lucidum is also traditionally used in the treatment of hepatitis and in a clinical study of 355 cases of hepatitis B treated with Wulingdan Pill, of which G.lucidum is the major component, 92.4% of patients were reported to have positive results. Again, it appears that triterpenes are the key components.
HYPERTENSION - G.lucidum has a broad range of action on cardiovascular health. Polysaccharides and triterpenes isolated from G.lucidum have shown hyperlypidaemic, hypotensive, and anti-thrombotic effects while a polysaccharide preparation (Ganopoly) led to improved ECG and lowered chest pain, palpitation and shortness of breath in a double-blind, randomized, multi-centre study. Mild ACE-inhibitory activity has also been demonstrated for some of G.lucidum´s triterpenoid compounds.
INSOMNIA/ANXIETY - The traditional name ´spirit mushroom´ point to the sedative action of its triterpenoid components and many herbalists value its benefits in cases of insomnia. Christopher Hobbs recommends G.lucidum for deficiency insomnia while Mizuno recommends it for ´mental stabilisation´.
RHEUMATOID ARTHRITIS - G.lucidum´s combination of immuno-modulatory and anti-iflammatory action suggests potential application in the treatment of autoimmune conditions such as rheumatoid arthritis and a proteoglycan fraction from G.lucidum has been shown to inhibit production of rheumatoid arthritis synovial fibroblasts in vitro, in part through inhibition of the NF-kB transcription pathway.
NEURO-PROTECTIVE - Traditionally considered to promote longevity, G.lucidum extract has been shown to inhibit beta-amyloid synaptic toxicity with potential benefits in Alzheimer´s disease. Both polysaccharides and triterpenes from G.lucidum exhibit neuroprotective and anticonvulsant effects at levels of 10-80mg/kg while G.lucidum spores have shown ability to protect neurons from apoptosis and improve cognitive dysfunction in vivo.
ANTI-AGEING - Traditionally known as the ´mushroom of immortality´, G.lucidum´s broad-spectrum cardiovascular, neurological and immunological benefits, together with its support for blood sugar and cholesterol control, contribute to its anti-ageing properties.
Main Therapeutic Applications - Allergies, liver support, cancer (especially breast and prostate), hypertension, anxiety/insomnia.
Together with Cordyceps sinensis, G.lucidum has the most extensive range of indications and combines well with it in treatment of lung and liver conditions, as well as to provide all-round adaptogenic support.
Key Components - Triterpenes and polysaccharides.
Dose - Traditional materia medica recommend a dose range for crude G.lucidum of 3-15g/day in decoctions or 1.5-3g as powder or in pills while doses of up to 30g/day have been reported and 5.4g/day of polysaccharide extract and 3.0g/day and G.lucidum spore powder have been used in clinical trials.
Dose range for dual-extraction products combining polysaccharide-rich hot-water and triterpen-rich ethanolic (alcohol-based) extracts is typically 1-3g/day while 500-1.000mg/day is normal for G.lucidum spore oil products.
Caution - Patients on anti-coagulant medication should be monitored due toG.lucidum´s actions in this area although a study of G.lucidum supplementation (1.5g/day) in healthy volunteers showed no effect on haemostatic function.
10. Shiitake – Xiang Gu
L.edodes is an important ingredient in Asian cuisine and its annual production (2 million tones) is second only to the common button mushroom (Agaricus bisporus). As well as being delicious, it has an excellent nutritional profile with high levels of B vitamins and pro-vitamin D2 (ergosterol).
Lentinan, a highly purified polysaccharide from L.edodes, is licensed in Japan for the treatment of gastric cancer and L.edodes is also one of the main species from which the popular mushroom α-glucan extract AHCC (Active Hexose Correlated Compound - reported to be the second most widely used supplement by cancer patients in Japan after Agaricus subrufescens) is derived. L.edodes is also the source of LEM, a crude mycelial extract containing glycoproteins, nucleic acid derivatives, vitamin B compounds and ergosterol with proven immuno-modulating properties.
Other bioactive compounds from L.edodes include eritadenine, which shows promise for lowering cholesterol levels, and Lentin, an anti-fungal protein, which also inhibits HIV-1 reverse transcriptase activity and proliferation of leukaemia cells.
CANCER - Analysis of 5 clinical trials with a total of 650 participants shows that the addition of Lentinan at 2mg/week to standard chemotherapy offers a significant advantage over chemotherapy alone in terms of survival for patients with advanced gastric cancer, patients with lymph node metastasis having slightly better results than patients without.
Additional trials confirm increased survival, reduced side effects from chemotherapy and improved quality of life in patients with colorectal, hepatocelluar, oesophagel, breast cancer and metastatic prostate cancer. In a trial with 69 metastatic prostate cancer patients the 50% survival lenght of treated and control patients was 48 and 35 months respectively, while the five-year survival rate of treated patients was 43% against 29% in the control group.
Although usually delivered by injection, Lentinan is also orally bioavailable although the clinical dosage is likely to be significantly higher.
Clinical trials using AHCC, a polysaccharide extract from multiple mushroom species including L.edodes, have shown positive effects in a number of cancers including breast, prostate and liver with reduction in side-effects from conventional treatment and improvement in haematopoetic parameters and cancer markers at a dose of 3g/day.
CHOLESTEROL CONTROL - Eritadenine has been shown to be a potent inhibitor of S-adenosylhomocysteine hydrolase and to accelerate excretion of ingested cholesterol and its metabolic decomposition. When added to the diet of rats (0.005%), eritadenine caused a 25% decrease in total cholesterol in one week.
Early studies indicated that levels found in whole shiitake mushrooms were too small to have a significant effect but recent research has shown the presence of eritadenine at levels 10 times higher than originally thought, indicating therapeutic possibilities for shiitake, particularly in cases where patients have shown statin intolerance.
In clinical trials dried L.edodes (9g/day) decreased serum cholesterol 7-10% in patients suffering from hypercholesterolemia and 90g/day fresh L.edodes (equivalent to 9g/day dried mushroom) led to a decrease in total cholesterol of 9-12% and triglycerides of 6-7%.
HEPATITIS B - Polysaccharide extracts from L.edodes have been shown to have broad anti-viral and hepatoprotective properties. In a study of 40 patients with chronic hepatitis B, LEM at 6g/day for 4 months led to improved liver function and resulted in 17 patients becoming seronegative for Hbe antigen (HbeAg).
HIV - LEM increased the T-cell count in HIV patients with AIDS symptoms from 1250/mm to 2550/mm after 60 days.
CANDIDA - In vitro studies show L.edodes to have consistently high leves of antimicrobial activity, including the highest anti-candidal action among several mushroom species.
Main Therapeutic Application - Cancer, cholesterol control, especially as an adjunct to statins.
Key Components - Polysaccharides and eritadenine.
Dose - 2-6g/day polysaccharide extract for immune support. 9g/day dried fruit body for cholesterol control.
Because eritadenine´s cholesterol-lowering
actioon differs from that of prescription statins or natural sources of statins
such as Pleurotus ostreatus or Monascus purpureus, it can usefully be combined
with them in cholesterol control protocols.
Safety - Although there have been a number of reports of dermatitis (Shiitake Dermatitis) developing following consumption of L.edodes these have been related to consumption of the raw mushroom and no cases have been reported for the use of L.edodes in supplement form.
11. Snow Fungus – Cloud Ear – Hakumokuji – Bai Mu Er/ Yin Er
------------------------------------------------------------------------------- for specialists in english
As well as being a popular culinary mushroom in oriental cuisine, T.fuciformis has a long history of medicinal use and was one of the mushrooms included in the Shen Nong Ben Cao. Its traditional indications include clearing Heat and Dryness, nourishing the brain and enhancing beauty.
Like other jelly fungi, T.fuciformis is rich in polysaccharides and these are the main bioactive component. The principal polysaccharide is a glucoronoxylomannan with a linear backbone of 1.3 linked α-D-mannan residues with side chains consisting mainly of xylose and glucoronic acid. The glucoronic acid side chains in Auricularia auricula have been found to be essential for its anti-coagulant action and they are likely to contribute to T.fuciformis´s action in this regard.
Research in China has focused on its use to alleviate the side effects of radiotherapy and as an anti-ageing supplement with over 40 Chinese patents citing it during the 1990s alone.
RADIOTHERAPY - As well as demonstrating broad immuno-modulatory activity and in vitro anti-cancer activity, T.fuciformis polysaccharides have been shown to protect against the consequences of acute radiation exposure, restoring the blood-producing mechanism of the bone marrow. When administered at a dose of 54mg/kg i.p. for 3 days before γ-irradiation they resulted in 50% 30-day survival in mice exposed to whole body lethal γ-irradiation compared to 100% mortality without and when administered at a dose of 200mg/kg for 3-5 days prior to γ-irradiation they exerted a protective effect on bone marrow with myeloid granulocytes reduced to 60% of normal compared to 20% of normal without. They also significantly increased 30-day survival rates in mice, dogs and monkeys exposed to γ-irradiation.
CIRCULATORY DISORDERS - T.fuciformis polysaccharides have been shown to stimulate DNA synthesis in vascular endothelial cells, the dysfunction of which is a major factor in the patogenesis of atherosclerosis, hypertension and trombophlebitis, with therapeutic implications for these conditions. They have also been shown to protect endothelium cells from histamine damage, increase clotting time, reduce platelet adherence and blood viscosity.
NEUROLOGICAL DAMAGE - The water extract of T.fuciformis (0.01-1 microg/ml) promoted neurite outgrowth of PC12 cells in a dose dependent manner , indicating potential for application of T.fuciformis polysaccharides in the treatment of neurological damage.
Experiments with mice also showed the ability of T.fuciformis polysaccharadise to exert an anti-ageing effect by increasing the superoxide dismutase activity of the brain and liver.
MEMORY IMPAIRMENT - Traditionally considered to nourish the brain, supplementation with T.fuciformis polysaccharide extract (100 or 400 mg/kg) for 14 days significantly reversed the scopolamine-induced deficit in learning and memory in rats and alleviated decrease in cholinergic immuno-reactivity induced by scopolamine in the medial septum and hippocampus.
COSMETIC APPLICATION - T.fuciformis has traditionally been used to benefit the skin and ´enhance beauty´ and T.fuciformis polysaccharides have been developed for use in cosmetic on account of their excellent skin moisture retention, skin protection, flexibility and flattening effects, as well as anti-inflammatory and anti-allergenic properties. Their ability to prevent senile degeneration of micro-vessels helps maintain blood perfusion to the skin and they have also been shown to promote wound healing.
Main Therapeutic Application - Immune support, anti-ageing, radiotherapy.
Key Component - Polysaccharides.
Dose - 1-3g/day polysaccharide extract for health maintenance, 3-6g/day for radiotherapy support.
T.fuciformis polysaccharides are beneficial for counteracting the harmful effects of radiotherapy and also possess excellent anti-ageing activity with a combination of neurological, circulatory and immune-modulating benefits. In addition they are an ideal supplement for those who smoke because of their moistening and nourishing properties, as well as beneficial effects on the skin and immune systems.
Safety - Although a widely consumed culinary mushroom with no reported side-effects, T.fuciformis´ mild anti-coagulant activity indicates a need for caution when using alongside anti-coagulant medication.
12. Sun Agaric - Himematsutake - Cogumelo do Sol
------------------------------------------------------------------------------- clinical guide for specialists
Although commonly known as A.blazei Murrill (ABM), after a mushroom discovered in 1945 by the mycologist William A.Murrill growing on the lawn of his friend R.W.Blaze in Florida, the mushroom used therapeutically can be traced to spores and samples sent to Japan from the Piedade region of Brazil by a farmer of Japanese descent in 1965. It is now believed that the two are in fact different species with the same Agaricus brasiliensis proposed for the Brazilian mushroom. Recent analysis however, indicates that this is the same mushroom identified by Charles Horton Peck in 1893 and called A.subrufescens and that this name should therefore have precedence.
Although one of the newest medicinal mushrooms, A.subrufescens is rapidly becoming one of the most popular. Reported in a recent survey as being taken by 31% of urological cancer patients in Japan, with the fastest growing US sales of any medicinal mushroom and one of the three most popular medicinal mushrooms in Taiwan, this relative of the common button mushroom, A.bisporus, exhibits broad clinical activity.
Its polysaccharides include several immunologically active low molecular weight fractions, while an α-1.6 and α-1.4 glucan complex, several polysaccharide-protein complexes, a glucomannan with a main chain of beta 1.2 linked mannopyranosyle residues and a heteropolysaccharide composed mainly of glucose, arabinose and mannose all show anti-tumour activity. Interestingly there appears to be an increase in structural diversity of its polysaccharides with maturation of the fruiting body.
A.subrufescens also contains high levels of lipids, including linoleic acid, oleic acid, stearic acid and ergosterol.
CANCER - A.subrufescens polysaccharide extracts show strong in vitro and in vivo activity against a range of cancer cell lines, including lung and ovarian cancer, and in vivo studies show positive results for Ehrlich ascites cancer, Sarcoma 180, human ovarian cancer and mouse lung cancer cell lines, as well as synergistic benefits with chemotherapy and radiotherapy.
In a rat cachexia model A.subrufescens extracts, as well as powdered fruiting body, significantly reduced tumour size and promoted gain in body weight with reduction in AST levels and increased glycaemia, while an in vivo study using severely immunomodificient mice found A.subrufescens polysaccharides to directly inhibit the growth of prostate cancer cells via an apoptotic pathway and to suppress prostate tumour growth via anti-proliferative and anti-angiogenic mechanisms with the greatest activity found in the broth fraction (compounds extracted from the liquid growth medium in which the mycelium was grown) rather than the mushroom itself.
A 2008 study reported significant increases in the NK cell activity of human volunteers given A.subrufescens polysaccharide extract at a dose of 3g/day compared to placebo, while Ahn reports increased NK-cell activity and reduced chemotherapy-related side effects (appetite loss, alopecia, emotional stability and general weakness) from A.subrufescens polysaccharide extract in one hundred cervical, ovarian, and endometrial cancer patients treated either with carboplatin plus VP16 (etoposide) or with carboplatin plus taxol.
In two small Chinese clinical studies, a dose of 20g A.subrufescens fruiting body, taken twice daily as a tea, was reported to improve haematopoietic parameters and treatment outcomes in patients receiving chemotherapy for acute non-lymphocytic leukaemia in one study and improvement in immune status, haematopoietic parameters and quality of life measures in late stage alimentary tract tumours in another.
The closely related A.bisporus shows in vitro anti-aromatase activity, with conjugated linoleic acid identified as the main active component, and Mizuno reports positive clinical results with A.subrufescens in a number of mainly breast cancer patients but at unspecified dosage.
Although most of the published research strongly supports the use of A.subrufescens in cancer therapy, two studies looking at the protective properties of A.subrufescens have been published with negative outcomes (in one A.subrufescens given at 5% of diet did not have a suppressive effect on colon carcinogenesis in rats exposed to dimethylhydrazine, in another an aqueous extract did not affect the development of liver cancer induced by diethylnitrosamine). In a third study A.subrufescens supplementation failed to produce significant change in TNF-α, IFN-γ or IL-10 levels in immunosuppressed mice and it appears that there may be significant variation in activity between different extracts, as well as between different strains.
DIABETES - To date little clinical data has been published although 2008 study reported decreases in cholesterol and glucose levels together with increased natural killer cell activity at a dose of 3g/day polysaccharide extract.
ALLERGIES - As potent immune modulators mushroom polysaccharides can reduce the level of Th2-mediated allergic reactions and A.subrufescens is no exception with Andosan, a proprietary combination of polysaccharide extracts from A.subrufescens (82%), H.erinaceus (15%) and G.frondosa (3%), causing a shift towards a Th1 cytokine profile with consequent reduced risk of allergies and in vitro inhibition of histamine release from mast cells.
HEPATOPROTECTIVE - There is evidence from a number of small clinical studies indicating possible application of A.subrufescens in the treatment of chronic hepatitis. In one study 1500mg of polysaccharide extract produced significant reductions in liver enzymes in a small number of hepatitis B patients over a 12 month period (AST reduced from 246 to 61 and ALT from 151 to 46). In another A.subrufescens extract reduced GTP in 80% of 20 patients with hepatitis C. Wang et al also reported wide-ranging benefits in patients with chronic Hepatitis B at a dose of 20g fruiting body twice a day over a 3 month period, including reduction in abdominal distension, fatigue and hepatodynia, together with increased retraction of the liver and spleen.
One in vivo study also indicates therapeutic potential of A.subrufescens polysaccharide extract for alcoholic liver injury with 100mg/kg body weight producing improvements in liver enzymes as well as liver histology and mitochondrial membrane potential.
Main Therapeutic Appliocation - Cancer
Key Component - Polysaccharides
Dose - 3g/day polysaccharide extract has been used in clinical trials but the high activity of the culture broth also supports the use of mycelial biomass or of mycelial biomass/polysaccharide extract combinations
Safety - Although A.subrufescens (like the common button mushroom A.bisporus) contains agaritine, a hydrazine-derived mycotoxin and group 3 carcinogen, this rapidly oxidises on exposure to air and during cooking with multiple studies confirming the safety of A.subrufescens as a functional food.
One animal study showed A.subrufescens to enhance local and systemic inflammation with possible implications for development of atherosclerosis although a randomized clinical trial in elderly women showed no changes in cytokine levels.
Another report suggested a possible connection between consumption of an A.subrufescens extract and three cases of hepatic dysfunction in cancer patients, although the authors state that several other causative factors cannot be completely ruled out. Cheilitis due to an A.subrufescens extract has also been reported.
PS-7 is combination of seven mushroom hot-water extracts with purified beta-glucans from S. cerevisiae. Contains 50% soluble polysaccharides (beta-glucans/ proteoglycans). PS-7 is made up exclusively of polysaccharide-rich hot-water extracts from seven mushrooms: Agaricus subrufescens (Agaricus blazei), Ganoderma lucidum (Reishi), Grifola frondosa (Maitake), Lentinula edodes (Shiitake), Phellinus linteus (Mesima), Trametes versicolor (Coriolus), Tremella Fuciformis (Snow Fungus), with additional beta-glucans from Saccharomyces cerevisiae. The high concentration and diverse structures of beta-glucans and related polysaccharides that it contains are ideal for broad activation of the immune system in chronic immune deficient conditions. PS-7 also provides immune support during conventional treatment.
14. IS Complex
IS Complex combines polysaccharide-rich extracts from four mushrooms (Maitake, Reishi, Chaga and Shiitake) with Ophiocordyceps sinensis biomass, EGCG (Epigallocatechin gallate) and food-state Vitamin C. Cordyceps has a profoundly energising effect on different aspects of the body, at least some of which may be accounted for by its ability to stimulate in-vivo corticosterone production. It also contains a diverse array of secondary metabolites including nucleoside derivatives, which have been shown to interfere with DNA replication in tumour and virally infected cells. Immune-modulating mushroom polysaccharides help to support effective immune response and their health benefits have been shown to reinforced by vitamin C. EGCG is the main antioxidant from Green Tea. It has been shown to inhibit growth and induce apoptosis in human cancer cell lines and also to inhibit viral binding to cell membranes. Extracts of Chaga and Reishi also supply betulinic acid derivatives, ganoderic and lucidenic acids. Mushroom extracts with Cordyceps biomass, Green Tea extract and food-state vitamin C for all-round support.
15. Red Yeast Rice complex: Hong Qu Mi
Red Yeast Rice extract standardised to 1.6% Monacolin K in combination with Shiitake optimized mycelial biomass and Co-enzyme Q10. Each capsule contains 5.6mg Monacolin K and 50mg CoQ10. Multiple research papers confirm the benefits of Monascus purpureus and Lentinula edodes for maintaining healthy cholesterol levels. The Red Yeast Rice (Monascus purpureus) used in Red Yeast Rice Complex is standardised to 1.6% Monacolin K, and is free from citrinin, a potentially harmful component of some Monascus purpureus containing products. We also add 50mg of CoenzymeQ10 per capsule to avoid possible depletion of this vital nutrient by statin-class compounds. Contents per capsule: 350mg Monascus purpureus, 100mg Lentinula edodes, 50mg Coenzyme Q10. NOT AVAILABLE IN THE USA
16. Reishi-Cordyceps Complex
Cordyceps mycelial biomass with Reishi hot-water extract and Reishi ethanolic extract. Both Reishi and Cordyceps are well known for their hepatoprotective properties and for their ability to support lung function. The triterpenoid ganoderic and lucidenic acids in Reishi also have proven anti-inflammatory and anti-histamine properties. In addition, this complex provides all-round support for energy and immune function and as such is an excellent supplement for those with hectic lifestyles.
17. Reishi-Curcumin Complex
Extracts of Ganoderma lucidum (3% triterpenes), Curcuma longa (95% curcuminoids), Boswellia serrata (60% boswellic acid) and Harpagophytum procumbens. Our proprietary blend of reishi with complementary herbs for maximum anti-inflammatory support. Helped by: on osteoarthritis, rheumatoid arthritis, osteophytes.
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