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Introduction

Professional level journal article

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Introduction

Maitake is a medicinal mushroom native to North America, Europe, and Asia. Its common name in English, “Chicken of the Woods,” hints of something the European villager has known for centuries. It tastes like chicken when cooked. It was the preferred mushroom of the Roman dining table and is still considered to be one of the finest wild mushrooms. Its incidence in the woodland is rare and always has been. Because of its scarcity, until recently, it was only available to those who would scour the woods in search of it.

Not long ago, Japanese research revealed the secret of the Maitake life cycle. From this revelation, they devised a system to grow Maitake commercially. Shortly thereafter, Maitake went from a hard to obtain delicacy to a reasonably available product. As this mushroom is known as “Chicken of the Woods” in English speaking countries, you may be wondering why it is better known by its Japanese name. In short, the Japanese were the first to produce it commercially and export it, so the Japanese name has won out over the English name. Japan continues to be the primary source of Maitake and indeed the Maitake you have received is imported from Japan.

Maitake is a member of the Polyporacea family of mushrooms. This family is of great interest to those working in herbal medicine, as many of its family members have been used for centuries to treat viral disease. Old herbals from Europe, America, and Asia are filled with references to Polyporacea mushrooms being used to treat a variety of viral diseases, including chicken pox, influenza, hepatitis, herpes, measles, mumps, and the common cold. If the old herbals are trying to tell us something, it would be that this group of mushrooms contains something that inhibits viruses and limits viral disease.

The old herbals indicate that these mushrooms have been used for thousands of years to treat viral disease. We at “The Herbalists” feel that where there is smoke, there is fire. People would not have used these mushrooms for all those years if they did not have a beneficial effect in viral disease.

Fortunately, our story does not stop with the old herbals. Scientists picked up on these clues and conducted extensive animal research to see if there was any truth to these traditional uses. This contemporary research showed that this group of mushrooms stimulated the natural defence system of animals against viral disease. Specifically, these mushrooms were shown to stimulate the production of NK cells, the white blood cells responsible for attacking viral invaders. Beyond this, experiments showed that these mushroom also stimulate the body to produce more interferon, which helps keep viral disease under control. Of all the Polyporacea family members, Maitake was shown to be the most powerful immune stimulant.

It was this combination of historical use and compelling contemporary research that lead us at “The Herbalists” to look at Maitake as a potential immune stimulant. We began using it in a wide variety of cases in which immune suppression was at the root of the problem. We found that when using Maitake, many people suffering from conditions like chronic sinusitis, chronic tonsillitis, chronic bronchitis, chronic cystitis, herpes, constant colds, and post-viral syndrome improved. In time, it has become our herbal medicine of choice when dealing with patients complaining of conditions relating to poor immune function. Although we do use other herbal supplements, Maitake continues to be our first choice for this complaint.

One of the questions frequently asked by our patients is as follows: “What can I expect from Maitake?” This is a difficult question to answer, as no two people are exactly alike. Our experience has been that most people respond to Maitake, some quickly, some slowly. As is true with most herbal medicines, Maitake does not work overnight. Those who persist with it for several months seem to fare better than those who try it for a week and give up. It is not a short term solution for what can be a long term problem. We suggest that our patients use Maitake for three months before they decide if it is making sufficient difference to continue.

We recommend that people suffering from poor immune function start using Maitake in low doses and gradually work up to the recommended dose of six tablets per day. We think the best plan of action is to start taking one tablet a day for the first two days; then increase the dose each day by one tablet until you reach six tablets per day.

We suggest this slow approach because Maitake contains a natural sugar, mannitol, which is known to act as a laxative and diuretic. Many people notice that they go to the toilet more often when they first start taking Maitake, and in some cases this is a welcome change. Starting slowly allows the body to adjust to an entirely new substance. Maitake is perfectly non-toxic and safe, in fact it is the preferred supermarket mushroom in Japan. Where we have the button cap, they have Maitake. However, a bit like prunes, Maitake does seem to get the body moving. As health depends upon the excretion of waste, this is always a good thing! However, this is just a pleasant side effect.

Poor immune function is the problem in the modern age. Practitioners see manifestations of this problem every day. Colds lasting for three months, herpes outbreaks that do not end, one urinary tract infection followed by another urinary tract infection, are all too common for the modern practitioner. The problem is poor immune function and the solution is the natural immune stimulants. Maitake is one of many agents that have been established to stimulate immune function and indeed it is seen as one of the best herbal medicines for the job!

QUICK REVIEW

History: Used as a food and tonic in Asia

Science: Contains complex sugars that stimulate immune function

Practitioners opinion: Excellent in viral disease of all descriptions

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Professional Level Article

Grifola frondosa: A Possible Addition to the Materia Medica

DR.Douglas Schar, BA, DipPhyt, MCPP

Abstract

Today, the European phytotherapist is entirely dependent upon one America plant, Echinacea purpurea, to stimulate the immune system. Since overdependence on a single drug, such as penicillin, has proven disastrous for the allopathic medical community, this article puts forth numerous reasons why Grifola frondosa (maitake) should be considered as a possible addition to the European immune system materia medica. These reasons include Grifola frondosa’s traditional use for centuries as an immune stimulant, its long term use as a benign food, contemporary research data showing its ability to stimulate immune cells, and its powerful anti-cancer activity. Beyond the dubious practice of Echinacea dependence, the phytotherapist has an increased need for immune stimulating drugs, since an increasing number of patients are presenting with depressed immune systems. It is time to explore the plants in our midst in the aim of finding Echinacea alternatives. The patient, our primary concern, will be the beneficiary of such an endeavour.

Introduction

At present, the European community of phytotherapists need to expand their list of immune system stimulating drugs. Today, the European Phytotherapist is entirely dependent upon one American plant, Echinacea purpurea, to stimulate the immune system.

It is a well recognized fact that no drug works with all patients. Whether a chemotherapeutic or phytotherapeutic drug, patient individuality results in a variety of responses to the same drug. A drug can work well with one patient, moderately with another, and not all with the third. By increasing our materia medica, we offer the second and the third patient an alternative to Echinacea purpurea.

Over dependence upon one drug has proven to be a disaster for the allopathic medical community. There is no reason to suspect that such a practice will work any better for the phytotherapist. The years of over dependence and over use of Penicillin and a handful of other antibiotics have achieved undesirable results to which all are familiar. And yet we are embarked upon a similar course. No one knows what the outcome of overusing Echinacea purpurea will be and there is no need for our community to tempt fate. Common sense says that putting all of ones eggs in one basket is a disaster waiting to happen.

Beyond the dubious practice of Echinacea dependence, the phytotherapist has an increased need for immune system stimulating drugs. An increasing number of patients are presenting with depressed immune system. Factors such as environmental pollution and stress, known to suppress the immune system, are unlikely to improve in the foreseeable future. As such, practitioners will continue to encounter immuno-incompetent patients and the situation may worsen before it improves.

Patients suffering from Hepatitis B and C, Herpes, HIV, and Chronic Fatigue Syndrome (Post-Viral Syndrome) are frequent attendants at surgeries of phytotherapists. Allopathic physicians and phytotherapists alike have noted the advantage of immuno-stimulants in these conditions, interferon and echinacea being two examples of commonly used drugs. Sadly, these pathologies are not disappearing and some suspect their incidence is on the raise.

Clearly, the immune system materia medica needs to be expanded so that more patients needs can be addressed. We have become reliant upon one American immuno-stimulating drug and are ignoring the wide range of European plants with similar activity. A more reasonable number of immune system stimulating drugs in the materia medica would be five or more. It is time to explore the plants in our midst in the aim of finding echinacea alternatives. The patient, our primary concern, will be the beneficiary of such an endeavour.

In this paper we will discuss one likely candidate for the expanded immune stimulant materia medica, Grifola frondosa. The drug is the fruiting body (mushroom) produced by the fungus. It is native to both the British Isles and Europe. For the purpose of this work, two were collected from Epping Wood in London. Records indicate that it was sold in the Roman markets as a delicacy and it is still one of the most popular wild mushrooms in Britain and Europe. Though it is currently relegated to the gourmet shop, studies over the last twenty years suggest that it might be better used as an immune stimulant.

In order to appreciate Grifola frondosa and its potential application in clinical medicine, it would pay to first examine the use of immuno-stimulant fungi in Europe. The historical developments which have lead to awareness of Grifola frondosa as an immune system stimulant will offer a useful introduction to one unknown drug that is a logical candidate for the materia medica.

Immunity Stimulating Fungi – Past, Present, Future

In Europe, several mushrooms have been used as panaceas with particular application in the treatment of poisoning, venomous bites, infectious disease, and loss of immune function. They were used to treat conditions that required on an active immune system, whether that was an infectious disease or a bite in which venom was injected into the body. They were called tonics and were used when a person faced what was formerly described as debility or loss of vitality. Today, we know “debility” often results from a failed or failing immune system.

The allopathic medical community often ridicules the lists of traditional uses of medicinal plants. Admittedly, claims that a mushroom was used to treat snake bite, tuberculosis, hepatitis, poisoning, influenza, debility, and rheumatoid arthritis seem a bit incredible. However, there is a common thread to all of these conditions. They are all caused by either a failing immune system or are improved by an active immune system. Many panaceas have in the laboratory proven to be immune system stimulants. This is the case with several European medicinal mushrooms.

For the ethnobotanist, it is interesting to note the use of medicinal mushrooms in Europe parallels the Native American use of Echinacea purpurea. Echinacea purpurea was used to treat rattlesnake bite, insect bite, wounds, burns, and coughs and colds. A list that, again, suggests its proven action on the immune system.

It would appear medicinal mushrooms have been used since the earliest day as medicine in Europe. In 1991, hikers discovered the remains of a man that died 3500 years ago in the Italian Alps. The discovery was well covered by the media though certain key facts were omitted. The frozen man had a medicine bag attached to his person which contained a pair of medicinal mushrooms. One has not been identified, the other was identified as Piptoporus betulinus (Bull. Fr.) Karst. (Polyporaceae).²⁸

Interestingly enough, Piptoporus betulinus, the Birch polypore, has been shown to contain polyporenic acid A, B, C. In tests conducted on animals polyporenic acid A has been shown to have an antimicrobial action.⁵ The fruiting body demonstrated antitumour activity³⁸ and induced interferon production in mice which had an antiviral effect.¹⁴ The Ice Age man was smart to carry a supply of this immunity stimulating mushroom in his medicine bag.

The four great ancient medical writers, Hippocrates, Pliny, Dioscorides, and Galen all spoke of the “tonic” properties of mushrooms. Hippocrates, father of western medicine (455 B.C.), discusses the use of mushrooms for the treatment of chronic disease. The main mushroom used by the ancients was Fomitopsis officinalis (Vill. Fr.) Bond. et Sing. (Polyporaceae) or the white agaric. The name agaric is as ancient as the use of this Polypore (Polypore – a member of Polyporaceae).

The mushroom was first called agaricum by Dioscorides (60 A.D.). At the time, the best samples of the drug came from Agraria in the Sarmatian region, hence the name agaricum. Dioscorides recommended its use in traumatic injuries including fractures and wounds, liver disease and jaundice, phthisis, poisoning and the bites of venomous animals.

Pliny (23-79 A.D.) wrote about this mushroom in his Natural History, reiterating the uses mentioned by Dioscorides. Pliny recommended it for the bites of spiders and scorpions, as an antidote in poisonings, to relieve fever, as a cure for tuberculosis, and as a treatment of jaundice.

The infamous Mithridate, allegedly first compounded by the King of Mithridate, contained Fomitopsis officinalis, amongst many other ingredients.²⁵ In the first Pharmacopoeia Londonensis, compiled in 1618, a recipe for mithridate including Fomitopsis officinalis can be found.³⁴ It was in this light that these medicinal mushrooms were seen in the ancient world, cure all’s and panaceas.

Though John Gerard is not accused of being an original thinker, his work does offer a window into the thinking of the medical community in the 17th century. He said this of Fomitopsis officinalis in his book written in 1633, “The same being inwardly taken and outwardly applied, is good for those that are bitten of venomous beasts which hurt with their cold poison, …It is good against shortness of breath, called asthma, the inveterate cough of the lungs, the ptysicke, consumption, and those that spet bloud.”

From the earliest day the white agaric was used to treat obstinate and hard shifted infectious disease like tuberculosis and hepatitis. What we now know is that this plant contains substances that stimulate the immune system into heightened action and thus these conditions are improved.³⁸ As we approach the modern age, we see another use of this drug.

Dr. Finley Ellingwood, MD., wrote this of Fomitopsis officinalis in 1905, “The remedy is applicable to all conditions of malarial origin. It is especially useful in those localities where malaria and the results of malaria prevail. The symptoms are languor, dullness, and general malaise, long continued with the usual results such as disordered digestion, lack of appetite, heavily coated tongue, pale mucous membranes. Usually there is a bitter taste in the mouth, often persistent, with constipation, and a dull, persistent headache. The temperature will be quite erratic. In some cases there is a little fever always present. In others, there is a marked intermission, or remission, may be irregular, not only in time but in amount.”

One of the common names for this mushroom, Quinine agaric, reiterates the above mentioned physicians thoughts about the drug. It was one of the ingredients in Warburg’s tincture (Antiperiodica tinctura) which was used extensively as a tonic into the 20th century. Warburg’s tonic can be found in the British Pharmaceutical Codex 1934 and white agaric is listed as one of the ingredients.⁹ The formula for this tincture is remarkable similar to that of Mithridate formulated by the ancients as an insurance policy against ill health.

It is interesting to note that as man has passed from generation to generation, medicinal mushrooms, like many of the plants we now call immuno-stimulants, have been used to treat the condition causing problems at the time. The ancient physicians patients were normally the nobility for whom poisoning was a constant threat. In Gerard’s day, overcrowding in cities lead to the spread of tuberculosis or consumption. The white agaric was used to suppress the symptoms of Tuberculosis. In the Victorian age, as world travel escalated and the tropical fevers became known to Europeans, once again, a medicinal mushroom was widely used in medical practice.

After the discovery of Penicillin’s activity against a wide range of bacteria, the medicinal mushrooms previously used in “folk medicine” became the objects of laboratory study. The work was centred on finding antibiotic substances in this group of mushrooms. Members of Polyporaceae, the most commonly used medicinal mushroom in Europe, demonstrated a number of members with antibacterial action.

Boletus Queletii: proved to be active against Staph. aureus.³⁶

Coriolus biformis: Contains polyacetylenic antibiotics such as biformine,biformic acid is active gram positive bacteria, gram negative bacteria, and fungi.³⁸

Coriolus consors: Contains coriolin and diketocoriolin B which inhibits the growth of gram positive bacteria.³⁸

Fomitopsis annosa: contains Fomannosin which shows toxicity to bacteria.³⁸

Piptoporus betulinus (Polyporus betulinus): The mushroom contains inhibitory chemicals to Micrococcus pyogenes, Bacterium racemosum, and Poliomyelitis.³⁸

Polyporus rutilans: Proved to be active against Staph. aureus.³⁶

Poria xantha: Proved to be active against Staph.aureus.³⁶

Polyacetylenes, phenolic compounds, purines, pyrimidines, quinones, and terpenoids found in mushrooms were determined to have an antibiotic effect.³ The fact that Polypores contain antibiotic substances partly explains their previous use in infectious disease.

The ancients use of these drugs in viral disease like hepatitis and influenza, would not be explained by the presence of antibacterial compounds. The poor immunity of the aged, another old indication for these drugs, would equally be unaffected by antibacterial substances.

However, as medicinal mushrooms were being examined for antibiotic substances a different line of research was taking place which ultimately would lead to a discovery that would explain these uses. In 1930, German researchers reported that extracts of several species of mushrooms had an anticancerous effect. Early on mushrooms in the Agaricus, Merulius and Phallius families proved to contain anti-cancer substances.³⁸

In 1950, German researchers found a water extract of Boletus edulis (Polyporaceae) to have a growth retarding effect on Sarcoma 180 tumours in mice. In 1959, other researchers refined Calvacin from Calvatia gigantea and determined that the substance inhibited the growth of Sarcoma 180 in mice.³⁸

The race was then on to find what chemicals in these mushrooms had this potentially magical action. The United States, Japan, and China, all took a great interest in these mushrooms. Some mushrooms families appeared to have an high percentage of members with this action. The Polyporaceae, the family to which Fomitopsis officinalis and Piptoporus betulinus belong, was a family noted to contain many members with an anticancer action. The list of members screening positive for anticancer activity included:³⁸

Bjerkandera fumosa: Used to treat uterine cancer in traditional medicine.

Coriolopsis occidentalis: Inhibited the growth of sarcoma 180 and adenoma 755 in white mice.

Coriolus consors: Anticarcinogenic to Ehrlich ascites carcinoma and leukaemia 1210 in white mice.

Coriolus hirsutis: A water extract has an inhibition rate 65% in sarcoma 180 in white mice.

Coriolus unicolor: Contains anticarcinogenic substances which inhibit Erhlich carcinoma in white mice.

Coriolus versicolour: An extracted polysacharide from the mycelium shows anticancer effect and is used as a anticancer drug in Japan. It has also been used in curing hepatitis B, chronic hepatitis, and curative medicine in cancer liver.

Daedalea biennis: An extract inhibits the growth of sarcoma 180 in white mice.

Daedaleopsis tricolor: A hot water extract had an inhibition rate of 36.5 – 90.0% the growth of sarcoma 180 in white mice.

Fistulina hepatica: Inhibited the growth 95% sarcoma 180 and Ehrlich carcinoma (90%) in white mice.

Fomitopsis cytisina: A cold water extract had a 70.2% inhibition sarcoma 180 and cold water extract had an inhibition rate of 44.2% in white mice.

Fomitopsis officinalis: It inhibits the growth of sarcoma 180 by 80%.

Fomitopsis pinicola: A water extract had an 51.2% inhibition rate of sarcoma 180 in white mice.

Fomitopsis rosea: Inhibition rate in sarcoma 180 in white mice of 70%.

Fomitopsis ulmaria: Water extract had a 44.8% inhibition rate in sarcoma 180 in white mice.

Ganoderma applanatum: Used in folk medicine for oesophageal cancer and had an inhibition rate of 64.9% in sarcoma 180.

Ganoderma boniense: Inhibition rate of 70% in sarcoma 180.

Ganoderma tsugae: Water extract inhibited the growth of sarcoma 180 and adenoma 755 in white mice. The sodium hydroxide extract had inhibition rate of 77.8% in Sarcoma 180 in white mice.

Lenzites betulinus: Used in leg and waist pain and problematic tendons. A methanol extract inhibited sarcoma 180 in white mice 23.3%-38%

Lenzites saepiaria: A liquid culture of fungus inhibited the growth of sarcoma 180 in white mice.

Lenzites trabea: A liquid culture of this fungus inhibited the growth of sarcoma 180 in white mice.

Phellinus gilvus: Inhibited sarcoma 180 up to 90% and Ehrlich carcinoma up to 60%.

Phellinus hartigii: The water and methanol extract inhibited sarcoma 180 67.9%-100% and Ehrlich carcinoma 90% in white mice.

Phellinus igniarius: The hot water extract inhibited sarcoma 180 in white mice was 87% and the water extract inhibited the growth of Ehrlich carcinoma 80% in white mice.

Phellinus linteus: A hot water extract inhibited sarcoma 180 by 96.7% in white mice.

Phellinus setulosus: Inhibited sarcoma 180 70% and Ehrlich carcinoma 60% in white mice.

Polyporus albicans: An ethanol extract inhibited Ehrlich carcinoma in mice and Yoshida sarcoma in rats.

Polyporus betulinus: A hot water extract to which ethanol was added resulted in crystals which had a inhibition rate of 49% in sarcoma 180 in white mice.

Polyporus frondosus (Grifola frondosa): A water extract inhibited Ehrlich sarcoma 98.1% in white mice.

Polyporus giganteus: A water extract inhibited Ehrlich sarcoma in white mice and had an inhibition rate in sarcoma 180 of 90% in white mice.

Polyporus umbellatus: An extract of the mushroom inhibited Sarcoma 180 in white mice 70%. It is used in clinical trials successfully for lung, cervix, oesophagus, gastric, liver, intestine, breast, cancer, leukaemia and lymphosarcoma.

Poria cocos: It had an inhibition rate of 96.88 in sarcoma 180 in white mice.

Poriah corticola: A fermented fluid inhibited sarcoma 180 and malignant adenoma 755 in white mice.

Poria subacida: Inhibited leukaemia L-1210 in white mice.

Pyropolyporus fomentaria (Fomes fomentarius): Used in dyspepsia and cancer of oesophagus, stomach, uterus. It inhibited sarcoma 180 80% in white mice.

Pyropolyporus rimosus: A water extract inhibited growth of sarcoma in white mice.

Trametes albida: Inhibited sarcoma 180 by 70%.

Trametes cinnabarina: Inhibited sarcoma 180 by 90%

Trametes dickinsii: A hot water extract inhibited sarcoma 180 in white mice by 41%.

Trametes gibbosa: A hot water extract inhibited sarcoma 180 white mice by 49%

Trametes orientalis: Its inhibition of sarcoma 180 was 80%.

Tyromyces pubescans: A hot water plus ethanol extract inhibited growth of sarcoma 180 in white mice 59.5%

Tyromyces sulphureus: Inhibited Ehrlich carcinoma in white mice.

Xanthochrous hispidus: It inhibited sarcoma 180 by 80% and Ehrlich carcinoma 70 %.

With such overwhelming evidence that members of Polyporaceae contained some compound or a series of compounds with an anticancer action, research continued. Initially, it was thought that these mushrooms contained cytoxic compounds that targeted cancer cells. As the work progressed, it became clear this was not the case.

A group of researchers in China investigated another Polypore, Polyporus umbellatus. It was established that the anticancer effect of this mushroom was due to stimulation of the immune system. Once researchers found that these mushrooms acted in cancer via the immune system, the whole range of mushrooms was once again subject to scrutiny. Trametes versicolour was shown to stimulate macrophage activity²² and Ganoderma lucidum was shown to strengthen the bone marrow.⁷

As mankind approaches the 21st Century, we are confronted with failing immune system. Once again, the medicinal mushroom and its immuno-stimulant action, can factor into the practice of medicine. Even allopathy has changed its focus in response to the crisis of the immune system and are investigating drugs that can assist the body fight its own battles. There is no doubt that medicinal mushrooms, panaceas from the past, will become household items in the next century.

It the midst of the flurry of research around Polyporaceae, Grifola frondosa came to the fore as a powerful immune stimulant. Early research showed that it inhibited sarcoma 180 by 98.1% as compared to the its others relations with significantly lower inhibition rates. These early findings resulted in a substantial amount of research into this European woodland resident.

The Botany of Grifola frondosa

Grifola frondosa’s Placement in the Fungal world

• Basidiomycotina
  • Hymenomycetes
    • Aphyllophorales
      • Polyporaceae
        • Grifola (Polyporus)

Scientific name: The current name for this plant is Grifola frondosa (Dicks; Fr., S. F. Grey). Until recently, it was known as Polyporus frondosa. Authors continue to use the two names interchangeably. Grifola is derived from the Italian word for a mythical beast (griffin). Frondosa refers to the frond like nature of the fruiting bodies produced by the fungus.

Common names: Grifola frondosa is called Hen of the Woods in Britain. In North America it is known as Hen of the Woods and or Chicken of the Woods. In France it is called Poule de Bois. In Japan it is called maitake. The western names refers to its similarity in taste to chicken.

Distribution: Grifola frondosa is a common mushroom that can be found growing in temperate deciduous forests in North America, Europe, and Asia.

Habitat: Generally, Grifola frondosa lives oaks, hornbeams, chestnuts, and maples. It can grow on any hardwood tree and occasionally coniferous trees. The mushroom feeds on lignin causing white heart rot. Incidence: There is great dissension as to whether Grifola frondosa is a rare or common fungus. Texts hold differing opinions. One British mushroom collector, Andrew Overalls, feels that it is common, but hard to find.

Life Span: Grifola frondosa is a perennial fungus mushroom and can live on the same tree for decades.

Fruiting Season: Grifola produces fruiting bodies in late summer and early fall. The fungus produces fruiting bodies irregularly.

Shape of Fruiting Bodies: Grifola frondosa is known as a bracket fungus and differs in physical form from the button cap mushroom. These mushrooms lack the traditional stem found on common mushrooms, instead hundreds of caps converge on a central base. Colour of the Fruiting Bodies: Grey, though the colour ranges from grey to dark yellowish brown to dark grey, occasionally creamy white.

Size of the Fruiting Bodies: One of the hallmarks of Grifola frondosa is its enormous size. The mycelium can spread over the entire trunk of a large tree and its roots. It can weigh 100 pounds and measure two feet across.

Texture of Fruiting Bodies: Most of the Polypores become wood like as they mature. Grifola, unlike its relations, is soft in texture, similar to a button cap mushroom.

Spores: Grifola frondosa produces spores copiously. They are 6.0 by 4.3 microns in size and white in colour.

Aroma: The fruiting body is noted for having a mouse like odour.

Chemical constituents of Grifola frondosa

Amino acids: Glutamine, alanine, threonine, asparagine, valine, lysine, arginine, serine. Research has shown that as the Grifola frondosa mushroom grows, the total protein content and free amino acid reduces by half.²⁰

Enzymes: Polysacharide hydrolases (Cellulase, hemicellulose, chitinase, amylase, pectinase); Lignin hydrolases (phenol oxidase, lactase, tyrosinase, peroxidase) and Proteases (aminoendopeptidase).²⁰

Lectins (Hemagglutinin): A glycoprotein known as maitake lectin. (Isoelectric point pH 5.9 and a saccharide content of 3.3%.).²⁰

Triglycerides: Grifola frondosa (maitake) contains 3.4% fat which puts it in the middle range of mushrooms in general. Octodecenoic and octadecadienoic acids being the major unsaturated fatty acids found in it.⁶ More specifically, Grifola frondosa (maitake) contains a wide range of fatty substances. Here is a short list of what has been found in this specific medicinal mushroom.

1. Neutral Triglycerides.
2. Sterol lipids: acylsterol, ergosterol, fungisterol, methylsterol.
3. Sphingo lipids: Ceremide (N-2′-hydroxy lignoseroyl-4-hydroxy-sph ingonine), Cerebroside (1-O-glucosyl-N’-hydrox ypalmitoyl-9-methyl-4-tra ns-8-sphingonine.²⁰
4. Phospholipids: phosphatidylcholine, phosphatidyl-ethanolamine (mycelium), and phosphatidyl-inositol, phosphotidylserine and phosphatidic acid.¹⁵

Vitamins and Minerals: Vitamin B1, B2, provitamin D, potassium, phosphorus, magnesium, calcium, sodium, and zinc.²⁰

*Grifola frondosa (maitake) contains metal bound proteins known to assist in the absorption of minerals across the intestinal wall and into the circulation. One of the problems with many of the metal minerals is the body has a hard time absorbing them.²⁷

Nucleotides: 5′-nucleotides (106-366 mg/100gm) including GMP.²⁶

Acids: Pyroglutamic acid, lactic acid, acetic acid, formic acid, malic acid, citric acid, succinic acid, oxalic acid, and fumaric acid.²⁰

Sugars: Trehalose, mannitol, chitin, Alpha and Beta-D-glucans.

Grifola frondosa

Until the mid 1970′s Grifola frondosa was collected from the wild and was only available in small and inconsistent quantities. As the result of investigation, mycologists discovered the secrets of this elusive mushrooms life cycles. They were able to simulate the conditions found in nature which stimulated the Grifola frondosa fungus to grow and produce fruiting bodies (mushrooms). The mushroom went from being rarely available to being available year round. It can now be purchased in grocery stores in the United States and Japan.

Commercial production of any of the immune stimulating Polypores is essential for any of them to be considered for use in phytotherapy. Mushrooms, by nature, are unpredictable and unreliable in producing fruiting bodies. Mushrooms collectors in Britain are quick to comment that Grifola frondosa is a common mushroom with the proviso that they have been known not to fruit for several years running. Availability must be a defining feature of the candidates for the European list of immuno-stimulant drugs. Many drugs are promising but lack of supply makes them of academic interest only.

The availability and early findings around Grifola frondosa, in Asia and North America, has made it a prime subject for research. Earlier work had established that mushrooms, like Grifola frondosa, acted in cancer via immune stimulation. In preliminary work, researchers established that Grifola frondosa was not a cytotoxic drug. They then established that when a Grifola frondosa extract was injected into mice tumours, the tumours shrank in size.^29,30 The suspicion being that, like other Polypores, Grifola frondosa acted as an anticancer agent via activation of the immune system.

In the aim of proving this, a number of experiments were conducted. As an example, in one experiment, the immune system of tumour bearing mice was blocked by the administration of an immune suppressive drugs (carrageenin, colloidal carbon, trypan blue). When these mice were injected with an extract of Grifola frondosa, the extract was not effective in inhibiting tumour growth. Tumour bearing mice were then given immune system stimulating drugs (thioglycollate medium or casein) after which an extract of Grifola frondosa was slightly more effective in reducing tumour size.^{23, 24}

It was concluded that Grifola frondosa activity in tumour suppression was linked to its effect on the immune system. Compounds found in Grifola frondosa were suspected to stimulate the immune system and in turn the immune system was then better able to contain cancer’s growth. Research then focused on the activity of Grifola frondosa on the immune system

An extract of Grifola frondosa was injected intraperitoneally into mice after they had been implanted with tumour cells (MM46, IMC carcinoma, and Meth-A sarcoma). The researchers concluded that the extract directly activated various immune cells. (macrophages, natural killer cells, and killer T cells). The extract also potentiated the activities of immune system mediators (lymphokines and interleukin-1). They found that under the influence of the extract, the immune cells were activated. This occurred even when an expected decrease in activity was anticipated.¹

Again in 1987, Takeyama et al. established that the anti-tumour effect of a Grifola frondosa extract was due to host mediated mechanisms involving both macrophages and T-cells. An extract of Grifola frondosa was injected intraperitoneally into mice implanted with tumor cells. (MM-46, Meth A fibrosarcoma, P815 mastocytoma). The extract was screened for cytotoxic activity and was found not to be cytotoxic. It was concluded that the antitumour effect of this extract involved both macrophages and T-cells.

In another study, powdered Grifola frondosa, fed to mice, enhanced the activities of macrophages (by 1.4 times), N-killer-cells (by 1.86 times), and cytotoxic T-cells (by 1.6 times). This lead to a 86% tumour growth in mice implanted with tumour cells as compared to a control group.¹⁷

Again in 1989, Suzuki et al., demonstrated that an extract of Grifola frondosa demonstrated significant antitumour effects in Meth A and IMC solid tumour systems in mice . The antitumour effect was shown to be as a result of enhanced activity of macrophages and Natural Killer cells. The extract was administered sub-cutaneously to the mice.

In yet another study, Adachi et al. (1989) demonstrated that macrophages, having been treated with an Grifola frondosa extract, consumed 50% more glucose. More over, under the extracts influence, macrophages had an enhanced synthesis and release of lysosomal enzymes. The extract increased macrophage cellular respiration and production of killer substances.

In 1990, Yamada et al., demonstrated that the oral administration of a Grifola frondosa extract potentiated the delayed hypersensitivity reaction to tumour antigens in mice implanted with tumours. The conclusion being the extracts action against tumours was in part due to a potentiated delayed type hypersensitivity reaction against the tumour antigens. The potentiated delayed type hypersensitivity reaction involved both macrophages and T-cells.

Studies indicate that in mice, Grifola frondosa stimulates the immune system. The stimulation is manifest in an increased activity of macrophages, T-cells, and Natural Killer cells. An element in the immune cell communication system, interleukin 1 and the lymphokines, are also stimulated under its influence. Bearing this in mind, it is not hard to imagine how such a drug could positively effect a wide range of conditions. Surprisingly, Grifola frondosa has not made its way into the European botanical materia medica. Indeed, most phytotherapists would not recognize it if they passed it in the woods. Despite all the encouraging evidence, there are several questions remaining in regards Grifola frondosa as a possible addition to the materia medica.

Are The AVAILABLE Studies Relevant?

Ethnobotanists and phytotherapists need to be discerning when it comes to studies confirming or condemning the use of traditional botanical drugs. Many of the studies are done using animals and involve the subcutaneous administration of the drugs in question. The relevance of a study where a drug is administered by syringe when the drug has been used as an oral medication in traditional medicine is questionable. Unless the study involves the administration of the drug in a manner similar to the traditional use of the drug, it can hardly be used to substantiate or refute the folk use of a drug. Phytotherapists do not always make the distinction or differentiation.

Most of the research done on medicinal plants is done by pharmaceutical concerns in search of a silver bullet, a magic cure for the pathology in question. The route of administration, more often than not, is subcutaneous. This appears to be the case with Grifola frondosa. Bearing in mind much of the research done on Grifola frondosa has involved subcutaneous administration of extracts of the drug, the relevance of this data to practising phytotherapists becomes suspect. The question, does it work when taken orally, needs to be asked.

As is not often the case, studies have been done that establish the immune system activation of Grifola frondosa takes place when the drug is administered orally. Here is a sampling of such studies.

• Researchers determined that extracts of Grifola frondosa were active against tumours when taken orally or when injected into mice.^{29, 30}
• The addition of powdered, dried, Grifola frondosa in the mouse food (20%) activated the immune response as well as stimulated a strong antitumour response.¹⁶
• It was determined that an extract of Grifola frondosa (D-fraction) was active against tumours when orally administered. With oral administration, activity of phagocytes and T cells was enhanced. The killing ability of both cells was improved, and the delayed hypersensitivity response was potentiated.⁸
• It was determined that the oral administration of an extract of Grifola frondosa potentiated delayed type hypersensitivity reactions of mice immune systems towards implanted cancer cells.³⁷
• An extract of Grifola frondosa (D-fraction) has been shown to have an antitumour effect in mice implanted MM-46 carcinoma and IMC carcinoma when given orally or injected.²¹

Grifola frondosa has been shown to have a stimulating effect on the immune system when orally administered. Though the history of the use of the Polypores suggests this must be the case, laboratory confirmation is encouraging.

The work done up to this point has been done on animals, largely mice, and the relevance of animal studies is widely debated. The acceptable standard is rising as the minutes pass. Certainly echinacea purpurea came into mainstream use with far fewer studies, also conducted on animals, which, at the time was sufficient. Oddly enough, those who use Echinacea purpurea with great regularity, and base their use on fewer studies, might not accept the admission of this plant into the materia medica. Phytotherapists must be cautious not let the standards raise to the extent reasonable admissions are overlooked.

The fact that Grifola frondosa is benign enough to be sold in supermarkets next to button cap mushrooms, combined with the animal studies available, indicate that it needs some review by the community of phytotherapists.

Is Grifola frondosa the best mushroom for the Phytotherapist to use as an immune stimulant ?

There are a number of European medicinal mushrooms available to the phytotherapists today. As a result of the increased interest in gourmet fungus, many mushrooms formerly gathered from the woods, can now be found at the grocery store. A number of immunity boosting mushrooms, Lentinus edodes (shitake), Pleurotus ssp. (oyster mushroom), and Tremella fuciformis (tree ear mushroom) are now available for the practice of medicine, all of which have been shown to have immune system stimulating activity. In fact, any of these mushrooms would be a welcome addition to the very limited immune system materia medica.

However, it would appear that Grifola frondosa is the most powerful stimulant of the immune system amongst the medicinal mushrooms now widely available. If one surveys the list of anticancer Polypores found earlier in this article, one will notice that where as most of the mushrooms rate of tumour inhibition hovered around the 60-70 percentile mark, Grifola frondosa achieved a inhibition rate of 98.1%. This high rate of tumour inhibition must correlate to its ability to stimulate the immune system. Several studies have established, In fact, Grifola is the superior anticancer drug.

In one study, when Lentinus edodes, Grifola frondosa, Agaricus bisporus, Pleurotus ostreatus, Flammulina velutipea, Pholiota glutinosa, Tremelia fuciformis, Auricularia minor, Volvariella volvaceae were fed to tumor bearing mice, Grifola frondosa most effectively retarded cancer growth.¹⁶

In another study, an extract of Grifola frondosa (D-fraction) was compared. Dr. Namba compared the action of Grifola frondosa with several extracts commonly used in the treatment of cancer in Asia. In mice, tumour reduction as a result of a Grifola frondosa D fraction was 86.6% compared with PSK (Trametes versicolour [-7.1%]) and lentinan (Lentinus edodes [54.4%]). The drugs were administered subcutaneously.²¹

Though comparative studies of the activation of the immune system by various medicinal mushrooms have yet to be done, work on the anticancer activity of Grifola frondosa suggests it may be the most powerful immune stimulant in Polyporaceae.

Active Constituents

It has been determined that the immune system stimulating action of Grifola frondosa depends on polysaccharides contained in the fruiting bodies of the fungus. Polysaccharide, protein bound polysaccharide fractions, and other sub-fractions in Grifola frondosa have been isolated and checked for immune system activation and tumour inhibiting action in animals. Though there may be other constituents contained in the fruiting bodies with immune system stimulating action, the polysaccharides are the only substances that have demonstrated this action up to this point.^{1, 10, 20, 30, 31}

Immune system stimulating sugars found in Grifola frondosa include:

1. Beta-D-glucan (Beta-(1-6)-branched Beta-(1-3)-D-glucan).
2. Beta-(1-6)-D-Glucan having beta-(1-3)-branched chain.
3. Alpha-D-Glucan.^{11, 13, 20, 35}

Grifola frondosa contains Beta-D-glucans and Alpha-D-glucans in two forms, laminaran type (native) and the curdlan type (helix).^{23, 24}

A potentially rewarding line of research would be the comparison of the polysaccharides found in Grifola frondosa as compared to those found in Echinacea purpurea. In that these two drugs have similar ethnobotanical profiles and have been determined to have similar activity in animal studies, there might be similarities in their chemical structure of their active constituents. Such a comparison could shed new light on both and the class of drugs in general.

Theories of how Grifola frondosa works

There is great debate as to how Grifola frondosa stimulates the immune system. As with the Echinacea purpurea, the are only theories at this point as to how Grifola works. Very little is known in real terms and the area is in need of further research. The theories around Grifola frondosa’s action may be of interest to some.

To recap that which we know; it has been demonstrated that extracts of Grifola frondosa suppress tumour growth via immune system stimulation when administered subcutaneously and orally in mice; the polysaccharides found in the fungus have been established to stimulate the immune cells in test animals. Whether or not the polysaccharides are absorbed, or even if they need to be absorbed, remains undetermined. The theories deal with basic issues such as absorption and continue through the compounds interaction with the immune system.

The Grifola frondosa immunity boosting polysaccharides are enormous molecules, molecular weights of 1,000,000 are reported for many of them. Molecules this size are not absorbed by the gut as from a physiological stand point, they cannot be. One theory holds that the bacteria in the gut cleave these sugars into molecules that are of an molecular weight that can be carried across the cell membrane. Theorists in Japan suggest that molecular weights of 35,000 are achieved through bacterial cleavage and these subunits are then taken into the circulation. Once these polysaccharide subunits are absorbed into the circulation, they are thought to activate the immune cells.

Some theorists suggest that the polysaccharides pass through the gut relatively unchanged and act without being absorbed. Upon encountering the immune cells found in the gut, they stimulate an immune reaction merely by coming into contact with the immune cells. The gut is noted for being populated by large populations of immune cells. The immune response starts in the gut with an interaction between these polysaccharides and immune cells and ultimately results in a systemic immune reaction.

One theory dealing with how the compounds found in Grifola frondosa wake up the immune cells deals with the chemistry of the sugars. This theory holds that the sugars are bound to proteins and once cleaved to size that can make it across the cell membrane, the sugar, attached to a protein, make their way into general circulation. The theory continues that the sugar/protein complex, once in the blood stream, is picked up by the immune system as being foreign or non-self, and an immune response is mounted.

Another theory around immune cell activation hinges on the notion that the molecular structure of Grifola frondosa’s sugar protein complex is similar to those found on the cell membrane of bacteria. When the immune system encounters these sugars they are duped into believing they have come across a virulent microbial invader. An alarm is sounded and the immune system mounts a response, though it is indeed a false alarm. As previously stated, these are only theories. There is much research that needs to be done.

Conclusion

Let us return to the original objective of this article; to review a possible addition to the European immune system materia medica. A number of factors have been brought forward that indicate Grifola frondosa is a likely candidate for admission to this materia medica.

1. Polypores have been used for centuries as immune system stimulants in traditional medicine in Europe.
2. Grifola frondosa is an article of diet and is benign enough to be distributed in supermarkets in Asia and North America.
3. It has been established, in animal studies, that Grifola frondosa activates macrophages, T-cells, and Natural Killer Cells.
4. It has been established that Grifola frondosa activates the immune system when administered orally.
5. In comparative studies with other medicinal mushrooms, Grifola frondosa has been established to be one of the more powerful anticancer agents amongst its relations and is possibly one of the strongest immuno-stimulant amongst the mushrooms.
6. Practitioners in America are using it in Viral conditions like HIV infection, ARC (Kaposi carcinoma), Viral Hepatitis, and in Chronic fatigue syndrome. They are using it in combination with other drugs in cancer and in cases of generally depressed immune systems. In preliminary clinical work, practitioners using the drug speak highly of it.

For all these reasons, Grifola frondosa seems a logical prospective candidate for the materia medica. Though all the facts are not known, certainly enough is known to suggest, at a minimum, its contemplation for admission. It could be argued that enough evidence is at hand for it to be used in clinical medicine.

This article hopes to raise several important issues beyond a possible addition to the materia medica. Firstly, we are badly in need of additional immune system stimulating drugs. Our dependence upon Echinacea purpurea is unacceptable and unnecessary.

Secondly, the process of discovery must not be stunted by the current trend towards absolute verification prior to the use of safe botanical drugs. This mentality would have denied plants like Echinacea purpurea admission to the materia medica. Echinacea purpurea was used by the plains Indians to treat snake bite, it was not used to treat recurrent tonsillitis. There are no studies indicating Echinacea works in infected tonsils, yet many person has been spared a tonsillectomy with its use. Countless patients have been helped by this plant, patients that might still be unwell if it were not for its use.

Certainly it is not being suggested that potentially dangerous drugs be used before substantial research is done into their possible side effects. However, Grifola frondosa is eaten as a food, it is clearly a benign drug. To deny it a place in the European materia medica would be a loss. The scientific process has its relevance, but trial and error also has a place. We must strike a balance between traditionally usage of botanical drugs and scientific research if we are to increase our materia medica. A combination of ethnobotany and scientific research could be a powerful combination in the effort to increase our materia medical.

Perhaps the first issue to be addressed is the creation of a reasonable criteria for the admission of “new” drugs into the materia medica. Whatever the process needs to be, the materia medica needs to be enlarged, and drugs like Grifola frondosa need to be reviewed.

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