Of all the Fu Zheng herbs, Ling Zhi or Reishi Mushroom is the most mysterious of all. Not only due to it's legendary qualities but also very much due to it's simple ability to calm the human mind and lend some clarity in an otherwise muddled existence. Practitioners are especially outspoken about Reishi. The early Chinese medical texts speak with genuine reverence about Reishi and it's powers to heal while the Taoists used it to lighten their selves and to become "capable of spiritual transcendence". This reference to Reishi is not by any means cultural. Although it has been known as the mushroom of spiritual potency in Asia, it has rapidly garnered a large following in the West amongst yoga, Tai Chi and meditation students. The first textual reports of Reishi record it as a "Shaman's Mushroom" or "Shaman's Ch'i". In fact it was originally called "Chih Zhi" or "Red Ch'i" (Chih=red, Ch'i=energy) and the red variety remains the most sought after for these reasons.

But it is the long chain polysaccharides that have attracted so much research in China, Japan and now the United States. These immunmodulators increase RNA and DNA in the bone marrow, increases interferon production, disrupting viral diseases and "smartening up" up the T-cells and expanding their "memory".

A study in 1982 in Japan showed 100% of test mice had complete regression in induced tumors. One of the constituents of Reishi which was studied was Beta-D-Glucan which holds the cell walls of grains intact. Triterpenes are another aspect of Reishi which has researchers scrambling. Shown to be the chief agent in Reishi responsible for lowering blood pressure and blood lipids, triterpenes are found in the fatty acid form as "lucidenic" and "ganoderic" acids. Ginseng also contains a similar compliment of these sterols and there is much speculation that these may be one of the crucial commonalties in longevity herbs.

Reishi and Ginseng also share the adaptogenic effect and protect against biological, emotional and environmental stresses. Reishi contains 112 known triterpenes which may be the cause of it's anti-hypertensive action. These triterpenes inhibit ACE, an enzyme (angiotensin converting enzyme) which many drugs attempt to control (with side effects). Reishi alleviates allergies, oxygenates the blood, relieves pain, reverses liver disease and is one of the most potent natural mood elevators known to man.

The various ganoderma are as follows:

g. lucidum (red) g. applanatum (brown) g.tsugae (red) g. sinense (black) g. oregonense (dark brown) The lucidum variety is the well known, modern type of Reishi which is being cultivated. The quality of the mushroom in terms of the effects are reliant on the conditions and environment of growth. This is the reason that wildcrafted Reishi is much preferred. Applanatum is the ancient Ling Zhi of legend, a stemless shelf mushroom which grows world-wide and has been recorded in weights up to 12 pounds. It's traditional name "Chih se lao mu chun" means "The flesh-like ancient source of life mushroom" Tsugae is much like lucidum except in appearance as it has a high gloss and is a bright orange-red.Sinense is a dark purple to black variety and is distinctive with it's longer stem (up to 8 inches). Oregonense is, as it's name implies a native of the western North America. It has not been studied for medicinal activity but it is assumed that it also contains similar properties.

Reishi is prepared, traditionally by powdering the mushroom and decocting at a low (sub-boiling) temperature for two to three hours or untill the original water level has been reduced by two-thirds.The tea is strained and can be sweetened with honey (sugar is not recommended). The powder (which is actually more like a wet "hair-ball") can be reused untill the tea has lost most of it's color, about three times. It has been recently found that long chain polysaccharides are utilized much more efficiently if taken within a few hours of ingesting vitamin C.

About Ganoderma Lucidum

Reishi - Ganoderma Lucidum

Other Common Names: Ling chih, Ling zhi, Mannentake, Ganoderma Lucidum

Western culture has often frowned on mushrooms, even fearing the small innocuous forest growth. The French prize their truffles, but even truffles and other edible fungi and mushrooms are not as highly valued or show as much potential as a species of mushrooms called Ling Zhi or Reishi.

Reishi mushrooms are polypore mushrooms. Mushrooms are the fruiting body and reproductive structure of a higher order fungus organism, much like an apple is the fruit of an apple tree. The actual mushroom "tree" is a fine thread-like network called mycelium. This mycelium is for the most part subterranean, living in soil, logs and other organic litter.

Unlike green plants, which produce many of their own nutrients by photosynthesis, mushrooms primarily get their nutrients from dead organic matter or soil. Mushrooms and their mycelium are nature's original recyclers. Without them, the planet surface would be piled high with dead, decaying material.

Mushrooms rise out of the mycelium when the right nutrients are amassed and the right environmental conditions are present. Mushrooms release spores at maturity. The wind spreads them and when they land on the right spot, the cycle starts over again.

Reishi often is associated with health and recuperation, longevity, wisdom, and happiness.

Known as reishi or mannentake to the Japanese and Ling Zhi to the Chinese, G. lucidum is renown for its medicinal properties. Reishi often is associated with health and recuperation, longevity, wisdom, and happiness. It is believed that certain triterpenes and polysaccharides may account for the multiple activities of Reshi. Thus, considerable time and effort has gone into the isolation and characterization of these compounds.

Reishi is a basidiomycete, lamellaless fungus belonging to the family of polyporaceae. In nature, it grows in densely wooded mountains of high humidity and dim lighting. It is rarely found since it flourishes mainly on the dried trunks of dead plum, guercus serrata or pasonia trees. Out of 10,000 such aged trees, perhaps 2 or 3 will have reishi growth, therefore it is very scarce indeed.

Relatively rare and undiscovered in the West, Reishi and other mushrooms have been revered as herbal medicines for thousands of years in Japan and China. Emperors of the great Chinese dynasties and Japanese royalty drank teas and concoctions of the mushroom for vitality and long life. The ancient Taoists were constantly searching for the elixir of eternal youth, and Reishi was believed to be among the ingredients.

Also called "God's Herbs", Reishi mushrooms are known for enhancing perpetual youth and longevity - the medicines of the legendary wizards.

In ancient time, reishi in medicine was considered so auspicious that its medical efficacy has been attested to in the oldest Chinese medical text (presumed to be over 2,000 years old). The book, which is known in Japan as "Shinnoh Honsohkyo", is now accepted as being the original textbook of Oriental medical science. In it, 365 kinds of medicines are classified and explained. The medicines are basically classified into three categories: 120 of them are declared to be "superior" medicines, another 120 are classified as "average" medicines, and the remaining 125 are placed in the "fair" category. The "superior" medicines are called "God's Herbs" and they are for perpetual youth and longevity - the medicines of the legendary wizards. The "average" category medicines are those which can be taken as a tonic, and those in the "fair" category are taken to remedy specific ailments. One must be careful about the volume taken of the "average" and "fair" category medicines, and should never take them continuously. However, the book states that for "superior" medicines, any amount can be taken as desired on a continuous basis with no unfavorable effects. Of the superior medicines listed in the text, reishi was rated number one.

Although Ganoderma and its derivatives are not pharmaceuticals and have not undergone rigorous clinical trials to be tested against cancer, there is abundant in vitro, animal and indirect clinical evidence to support its supplemental use in cancer. Standardization in bioactive polysaccharide content and dosages will be necessary to assure its rational use, and clinical trials in select cancers with defined endpoints will confirm its efficacy.

Former heart surgeon Dr. Fukumi Morishige, a leading authority on vitamin C in Japan, reports that when Reishi and vitamin C are combined the results against cancer and other diseases

are far better than when Reishi is ingested. This is because the vitamin makes the polysaccharides more accessible to the immune system.

Reishi has long been known to extend life span, increase youthful vigor and vitality. It also promotes good blood circulation by eliminating thrombi in the blood streams. As a result, the person feels renewed vitality. Deterioration of mind and body is arrested. Reishi is indeed a herb with multiple applications.

Chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] were compared using in vitro short-term screening methods associated with both initiation and promotion processes in carcinogenesis. In induction of glutathione S-transferase activity, GPS was found to be the most effective among plant polysaccharides. These results suggest that some plant polysaccharides produced both anti-genotoxic and anti-tumor promoting activities in in vitro models and, therefore, might be considered as potential agents for cancer chemoprevention.

Conclusively, clinical observations have indisputable proof of reishi's efficacy against cholesterosis, arteriosclerosis, hypertension, fatty liver, hemorrhoid, tooth-infections, obesity and various problems that arise from high serum cholesterol level compounded by a lack of blood circulation. Reishi is also recognized to have some effect in cases of stroke, cerebravascular accident, coronary insufficiency, myocardial infarction, phlebitis etc. - problems that arise directly from arterial blockage. Furthermore, it is found to be effective in treatment of typical dermatitis, bronchitis asthma, allergy rhinitis, chronic hepatitis etc. - problems related to allergic reactions. Reishi inhibits thrombi to facilitate medication absorption; it also has an additive effect that strengthens the prostate gland situated between the bladder and the urinary tract. It has the same effect on the early stage of diabetes mellitus. Bladder infection is accompanied by the usual thrombi formation. Treatments with reishi arrest the latter thus eliminating complications within a short period. Other clinical tests showed that administering reishi instead of insulin can reverse blood sugar level back to normal after one year.

The fruit bodies of Ganoderma lucidum have been used for the prevention and treatment of various diseases in the Orient. Its antitumor and immune enhancing properties, along with no cytotoxicity, raise the possibility that it could be effective in preventing oxidative damage and resulting disease. Using agarose gel electrophoresis, the potential of Ganoderma lucidum extract as a radioprotector and antioxidant defense against oxygen radical-mediated damage was evaluated. The results clearly demonstrate that the hot-water extract of Ganoderma lucidum shows good radioprotective ability, as well as protection against DNA damage induced by metal-catalyzed Fenton reactions and UV irradiation. The data suggest that Ganoderma mushroom merits investigation as a potential preventive agent in humans.

Administration of hot water soluble extracts of Ganoderma lucidum (36 to 72 g dry weight/day) decreased pain dramatically in two patients with postherpetic neuralgia recalcitrant to standard therapy and two other patients with severe pain due to herpes zoster infection.

This review highlights some of the recently isolated and identified substances of higher Basidiomycetes mushrooms origin that express promising antitumor, immune modulating, cardiovascular and hypercholesterolemia, antiviral, antibacterial, and antiparasitic effects.

Medicinal mushrooms have a long history of use in folk medicine. In particular, mushrooms useful against cancers of the stomach, esophagus, lungs, etc. are known in China, Russia, Japan, Korea, as well as the U.S.A. and Canada. There are about 200 species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. Searching for new antitumor and other medicinal substances from mushrooms and to study the medicinal value of these mushrooms have become a matter of great significance. However, most of the mushroom origin antitumor substances have not been clearly defined. Several antitumor polysaccharides such as hetero-beta-glucans and their protein complexes (e.g., xyloglucans

and acidic beta-glucan-containing uronic acid), as well as dietary fibers, lectins, and terpenoids have been isolated from medicinal mushrooms. In Japan, Russia, China, and the U.S.A. several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used to treat a variety of disease states.

As recorded in the oldest Chinese medical text, reishi is the "king of herbs", the superior herb for perpetual youth and longevity. Continuous intake will achieve the best results.

References

- Linda McGlasson, Assistant Editor. Health Foods Business/January 1992 Consumer Education Series. Reishi: Ancient Medicine Is Modern Hope- Kim HS, Kacew S, Lee BM. Carcinogenesis 1999 Aug;20(8):1637-40. In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus edodes, Ganoderma lucidum and Coriolus versicolor).- Kim KC, Kim IG. Int J Mol Med 1999 Sep;4(3):273-7. Ganoderma lucidum extract protects DNA from strand breakage caused by hydroxyl radical and UV irradiation.- Hijikata Y, Yamada S. Am J Chin Med 1998;26(3-4):375-81 Effect of Ganoderma lucidum on postherpetic neuralgia.- Wasser SP, Weis AL. Crit Rev Immunol 1999;19(1):65-96. Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. International Centre for Cryptogamic Plants and Fungi, Institute of Evolution, University of Haifa, Israel.

Health Benefits

Reishi: Ancient Medicine Is Modern Hope (Health Foods Business/January 1992: Consumer Education Series)

By Linda McGlasson, Assistant Editor

Western culture has often frowned on mushrooms, even fearing the small innocuous forest growth. The French prize their truffles, but even truffles and other edible fungi and mushrooms are not as highly valued or show as much potential as a species of mushrooms called Ling Zhi or Reishi (Ganoderma lucidum). The late Hiroshi Hikino, recognized as the world's authority on the chemistry of Oriental medicinal plants, called Reishi one of "the most important elixirs in the Orient." Relatively rare and undiscovered in the West, Reishi and other mushrooms have been revered as herbal medicines for thousands of years in Japan and China.

Emperors of the great Chinese dynasties and Japanese royalty drank teas and concoctions of the mushroom for vitality and long life. The ancient Taoists were constantly searching for the elixir of eternal youth, and Reishi was believed to be among the ingredients.

In modern times, Ganoderma lucidum and its fellow mushrooms have been well-researched in Asian universities. It is currently being studied in China as a sports performance enhancer. Its long History has sparked interest in the West where it is used by herbalists to treat diverse problems such as allergies, chronic Fatigue Syndrome, diabetes, liver diseases and many immune-related diseases. As little as 20 years ago, Reishi was rare and not widely found in Asia. It grew in the wild, but was extremely hard to cultivate. Now with an increased knowledge of the climates that it thrives in, scientists are able to set up artificial growth conditions with the correct amounts of oxygen and moisture for the spores to grow into the Reishi mushroom.

JUST ANOTHER FUNGUS?

Reishi mushrooms are polypore mushrooms. Mushrooms are the fruiting body and reproductive structure of a higher order fungus organism, much like an apple is the fruit of an apple tree. The actual mushroom "tree" is a fine thread-like network called mycelium. This mycelium is for the most part subterranean, living in soil, logs and other organic litter. Unlike green plants, which produce many of their own nutrients by photosynthesis, mushrooms primarily get their nutrients from dead organic matter or soil. Mushrooms and their mycelium are nature's original recyclers. Without them, the planet surface would be piled high with dead, decaying material. Mushrooms rise out of the mycelium when the right nutrients are amassed and the right environmental conditions are present. Mushrooms release spores at maturity. The wind spreads them and when they land on the right spot, the cycle starts over again.

REISHI'S MEDICAL PROPERTIES

In the 16th Century pharmacopedia Pen T'sao Kang Mu, which contains hundreds of natural medicines the Chinese have used for thousands of years, compiler Le Shih-chen described the uses of Reishi. "It positively affects the life energy, or qi of the heart, repairing the chest area and benefiting those with a knotted and tight chest." He wrote that it also increases intellectual capacity and banishes forgetfulness. "Taken over a long period of time, agility of the body will not cease, and the years are lengthened to those of the Immortal Fairies." In the Orient, Reishi is considered a Fu Zhen herb (immune modulation). Presently, Reishi has various applications including lowering or raising blood pressure, stimulating liver actions, blood cleansing, and acting as an adaptogen in helping the body fight the effects of stress. Chinese herbalists prize it for its abilities to regenerate the liver. In high doses, and to some degree normal doses, Ganoderma maybe classified as a liver detoxicant and protectant. In traditional Oriental applications Reishi is also used to treat insomnia, gastric ulcers, neurasthenia, arthritis, nephritis, asthma, bronchitis, hypertension and poisoning. It is also being used in treating neuromuscular disorders -- stress-induced tension, myasthenia gravis and muscular dystrophy -- all with varying degrees of success. Toxicity studies show no toxic effects on humans. In research, patients are given much higher doses, as high as 10 grams of extract per day, with no ill effects.

ACTIVE INGREDIENTS

The potency of Reishi mushrooms is usually based on its level of triterpenoids. One can determine the level of this by tasting it. The more bitter it is, the higher the level of triterpenoids. Because Reishi is a polypore, (a group of hard, woody, bracket-like mushrooms) it is not eaten, but cut into pieces and made into a tea. In China, the average dose is 3 to 5 grams a day. Other popular forms of delivery are the water/alcohol extracts and powders. Reishi mushrooms and mushroom extracts are generally analyzed for specific triterpenoids called Ganoderic acids. When buying a Reishi mushroom product, check for the analysis of

how much triterpenoids is in the extract or powder. "There is no standardization yet, either here or in Asia for Reishi. You have to look for high ganoderic acid-A levels, which indicates high levels of other ganoderic acids," said Kenneth Jones, a researcher/writer specializing in the ethnopharmacology of medicinal plants. One focus for future research is on Reishi spore extracts. In China, it has been used in injectable form in clinical treatments of various ailments with success. One of the things it has successfully treated is low energy, and debilitation following long illness.

OTHER APPLICATIONS

Chinese women take Reishi for beautification of the skin. The results are probably due to the mushroom's hormone-potentiating effects, Jones said.

Reishi is included in many Japanese patents for hair loss formulas, including products used for alopecia. Spore extract injections of Reishi are also being used to treat lupus in China. The mycelium of Reishi contains high levels of polysaccharides, which have been shown in research to induce the production of interferon. Interferon is a protein produced inside cells to fight viral infection. Polysaccharides are also tumor fighters and help stimulate the immune system. Reishi is being recognized for its adjunct use as an immune system stimulator when cancer therapy is being used. The use of Reishi as a cancer treatment in the Orient is centuries old. In following the concept of qi tonics, Reishi is used to strengthen the body's resistance to outside forces. Former heart surgeon Dr. Fukumi Morishige, a leading authority on vitamin C in Japan, reports that when Reishi and vitamin C are combined the results against cancer and other diseases are far better than when Reishi is ingested. This is because the vitamin makes the polysaccharides more accessible to the immune system. It is also an adaptogen, with properties similar to ginseng. The adenosine in Reishi may explain why the Chinese use it for patients suffering from nervous tension. Adenosine relaxes skeletal muscles, calms the central nervous system and operates against the stimulating action of caffeine. "Reishi mushrooms are certainly an herb for the 90s and beyond," commented Jeff Chilton, president of North American Reishi. "Considering that Reishi has a history of use that spans 2,000 years and is more highly revered than ginseng in the Orient, one could readily compare its potential to that of ginseng."

Contributing to this article were Terry Willard, Ph.D. and Kenneth Jones, authors of Reishi Mushroom: Herb of Spiritual Potency and Medical Wonder.

Health Benefits

Ganoderma lucidium has No Known Herb Drug Interaction

No Known Herb Drug Interaction For Ganoderma lucidium, Only a Drug Enhancing Effect

Ganoderma lucidium has a very prized and storied history. It has been used in Traditional Chinese Medicine for over 2000 years to help conditions ranging from fatigue to blood clots. In present times we are just starting to understand what is in Ganoderma that can help our health.

In general, Ganoderma has been shown to be safe and non toxic even at very high doses in animal and human studies. Our family has been enjoying Ganoderma's wonders for quite some time and have yet to experience any side effects.

There are some side effects and herb drug interaction (an enhancing effect) that you should be aware of and these will be discussed next.

What Are The Possible Side Effects Of Taking Ganoderma lucidium?

Side effects from the consumption of Ganoderma lucidium are very infrequent but may include:

dizziness dry mouth, throat, and or nose upset stomach diarrhea dermatitis

These side effects usually disappear in a week or two. Others may experience these side effects after prolonged use. Upset stomach can be avoided by taking Ganoderma with food. Some find relief from diarrhea by taking Ganoderma lucidium with vitamin C.

Please make sure to check with your doctor if you are pregnant, nursing or are planning on becoming pregnant.

Although allergic reactions are rare, Ganoderma lucidium contains agents that may be an allergen to some. Talk with your doctor if you are unsure before taking any supplement.

Another interesting bit of information is that there seems to be no cross-sensitivity to Ganoderma lucidium if a person is allergic to Button mushroom or the common white mushroom.

Still, please be aware that if you are sensitive to molds or other mushrooms please take the necessary precautions and discuss this with your health care provider before taking this or any other supplement.

Now that you are aware of the possible side effects, let's look at the possible herb drug interaction.

Herb Drug Interaction

There have been no known drug herb interactions, but high doses of Ganoderma lucidium has the potential to enhance the effects of:

antihypertensive medications hypoglycemic medications anticoagulant medications like warfarin or coumadin

So if you are taking these meds or any other medications, please talk to your doctor before taking Ganoderma lucidium.

Health Benefits

Ganoderma May Help Reduce Cholesterol

Cardiovascular disease has been called an epidemic of sorts in North America and Europe. Not surprising when you consider a typical North American lifestyle of not enough physical activity, diet high in saturated fats, and fast paced living driving up stress levels.

Even though the National Center for Health Statistics reported Americans average total cholesterol has dropped substantially from 1978 - 1990, the American Heart Association has reported 98.1 million adult Americans still have borderline high blood cholesterol levels and this puts them at greater risk of developing Cardiovascular disease.

Elevated cholesterol levels are one of the major risk factors identified by the American Heart Association in the development of Cardiovascular disease which is the number one killer in North America and Europe. We need to reduce cholesterol levels.

Adenosine which is found in Ganoderma lucidium helped to reduce cholesterol

This number one rated herb in Traditional Chinese Medicine has many potent healing properties. One being that it may help reduce cholesterol and or may help the liver in suppressing its production.

Researchers from the Beijing College of Traditional Chinese Medicine found that Adenosine which is found in Ganoderma lucidium helped to reduce cholesterol in their studies.

Researchers at the Nestle Research Center in Switzerland called Ganoderma lucidium "a renowed medicinal species". In their study on hamsters and minipigs, oxgenated lanosterol derived from Ganoderma lucidium "inhibited cholesterol synthesis".

With hamsters it was able to reduce cholesterol (total) by 9.8% and HDL levels by 11.2%.

In minipigs the oxygenated lanosterol derived from the mushroom Ganoderma lucidium was able to reduce cholesterol (total) by 20%, LDL by 27%, and HDL by 18%.

The researchers conclusion was that Ganoderma "has the potential to reduce LDL cholesterol in vivo (inside the body) through various mechanisms... innovative new cholesterol lowering foods and medicines containing Gl (Ganoderma lucidium) are envisioned."

Health Benefits

A Reishi Mushroom a Day May Keep the Doctor Away

By Dr. Cathy Sabota, Horticulture Specialist

During the past 50 years, Asian countries have conducted an abundance of research on the medicinal value of several edible mushrooms. Their claims include reduction of blood pressure and cholesterol, enhancement of the immune system, cancer therapy, antiviral and anti-inflammatory properties, treatment of anaphylactic shock, anti-HIV properties, increase of oxygen utilization, and antioxidant properties (Chen and Miles, 1996). Ganoderma lucidum (Reishi), Lentinula edodes (Shiitake), Hericium erinaceum (Lions Mane), Pleurotus ostreatus (Oyster mushroom), and Grifola frondosa (Maitake) are just a few of the cultivated mushroom species that have been analyzed for medicinal value.

In the United States (US), the phytopharmaceutical value of these mushrooms has only recently been recognized and clinical trials have been established to determine the medicinal characteristics of these mushrooms (Kimmons, 2003; Underwood, 2003). Shiitake mushrooms are the most common specialty mushrooms grown in the US. The principal medicinal component, a polysaccharide, has been identified as lentinan. However, reishi, maitake, oyster, and lions mane are also reported to have significant medicinal value. Over the next year each edition of this newsletter will document clinical trials or research recommendations for the use and effectiveness of various mushrooms. While the recommendations given by researchers are assumed to be accurate, you should always check with a physician before using any food supplements as alternatives to prescribed medications. Today's mushroom is Ganoderma lucidum (Reishi).

Ganoderma lucidum (Reishi) is documented to have medicinal value but its extract is considered as a nutriceutical. The medicinally effective component of mushrooms may vary depending upon what is to be treated. The actual level of these components in a measured volume of mushroom may also vary depending on how the mushroom was grown and the extraction process. It is important to know what dose works best for an ailment if it is intended to afford a cure or to alleviate certain sickness. Because the toxic, lethal and effective dosages are yet to be determined, the usual dosage given is generally based on personal experience with patients suffering from different illnesses (Soo, 2004).

In a recent study by Teow Sun Soo at the MARA Institute of Technology in Malaysia, Reishi was used in small clinical (12 to 48 human subjects per trial) trials to determine its effectiveness against various ailments. Each capsule contains 500 mg of reishi extract. The following discussion includes the recommendations made by Soo as a result of his research (Soo, 2004).

The reishi extract has been shown to be effective in completely curing migraine headaches. It is believed that oxygen shortage in the brain (hypoxia) is at the core of the pathogenesis of a migraine attack. Once a certain threshold of oxygen deprivation is reached, the migraine attack bursts out. The usual dose is 3 capsules, 3 times a day, before meals.

As an anti-inflammatory agent, the extract is effective in substantially alleviating the problems and pain related to rheumatism or osteoarthritis and gout. The patients should see significant effects within a week. The dosage is 3 capsules, 3 times daily, before meals.

In treating hypertension or hypotension the extract has been shown to be highly effective in a very large number of cases treated. In the more successful cases blood pressure is back to normal within 2 months and in some cases within 2 weeks. The recommended dosage is 1 capsule 3 times daily for five days, increasing to 2 capsules 3 times daily for one week and then to 3 capsules 3 times daily. It is very important that hypertension patients start with only 1 capsule as a higher dose might increase the blood pressure of the patient. Positive results should be obtained within 30 days. Once the desired fall in blood pressure has been achieved, the daily dose can generally be reduced. For maintenance therapy 2 capsules, 2 times daily are usually sufficient.

The extract has been found effective in reducing and in some cases eliminating asthma attack. The recommended dosage begins with 1 capsule 3 times daily for five days, increasing to 2 capsules 3 times a day for 1 week and then to 3 capsules, 3 times daily. It is important that the patient starts with a low dose as a higher dose might initially trigger an asthma attack.

The extract is effective in reducing blood sugar level and the amounts of insulin required for diabetic patients. The effectiveness of the treatment is reduced the longer the patient has been a diabetic. For non-insulin dependent patients it is possible to have a better cure. Patients should see significant effects within 1 to 2 months. The usual dose recommended is 3 or 4 capsules, 3 times daily depending on the severity of the condition.

The extract is effective in regaining stamina and energy or debility due to prolonged illness especially for cancer patients after undergoing radio and/or chemotherapy. They are able to eat and sleep well. The dosage is 2 capsules 3 times daily.

The extract is effective in clearing up a large variety of skin allergic conditions either due to food or airborne allergens. The dosage prescribed is 3 capsules, 3 times daily.

Ganoderma extract has been found to be useful in detoxifying the kidney and improving its overall function. Patients receiving hemodialysis should find that the duration and frequency of the treatment could be reduced. The usual dosage is 3 or 4 capsules 3 times daily depending on the severity of the condition for as long as required.

The extract has been shown to be effective in completely curing insomnia within one month in a very large number of cases treated. The usual dose is 3 capsules, 3 times daily.

The extract has been found to be effective as a hypocholesterolemic agent. The usual dosage is 4 capsules, 3 times daily. Patients should see results within a month.

The extract has been shown to be effective in relieving or eliminating constipation problems. The recommended dosage is 3 capsules, 3 times daily. The patients should see results within 1 to 2 weeks.

The extract has been found to be effective in reducing and also curing hemorrhoids depending on the severity of the case. Patients should see results with 30 days. The usual dose is 3 or 4 capsules, 3 times daily depending on the severity of the condition.

The extract has been shown effective in reducing or eliminating excessive menstrual pain and irregularities. Treatment has to be maintained for 2 or 3 cycles for it to be effective. The usual dosage is 3 capsules 3 times daily. Patient needs to stop taking the capsule during the actual period.

Ganoderma extract has been found effective in addressing a variety of cardiovascular problems. It improves the circulatory system with excess oxygen. It also eliminates the conditions of angina pectoris and palpitation. The recommended dosage is 1 capsule 3 times daily for five days, increasing to 2 capsules, 3 times daily for one week and then to 3 capsules 3 times daily. Patients should starts with only 1 capsule per dose as a higher dose might initially increase the blood pressure of the patient.

Ganoderma extract has been shown to be very effective in treating Lupus erythematosis autoimmune disease. Patients should take 3 capsules 3 times daily.

The extract is highly effective in improving and in most cases curing Hepatitis A, B, and C within a period of three months. The recommended dosage is 4 capsules 3 times daily. Patients should be cured within three months.

Ganoderma extract is effective in arresting epilepsy. Patients should take 3 capsules 3 times daily and may expect to see results after a week.

Ganoderma extract has also been found effective for both gastritus and gastric ulcer. The usual dosage is 3 capsules, 3 times a day after meals. Patients should see results in 3 to 4 weeks.

Ganoderma extract is useful for people leading a hectic life with heavy schedule. The usual dosage is 2 capsules, 3 times daily reducing to 1 capsule, 3 times daily for maintenance.

The experiences in fighting cancer are more inconsistent, however, extract has been shown to be effective in regressing tumors. The results depend on the type of cancer and the severity of the condition. It is recommended that it be used in combination with the prescribed therapy. The Ganoderma extract can be highly effective in substantially reducing or eliminating the side effects of radio and chemotherapies if it is taken preceding, together and after the treatments. It can prevent side effects like hair loss, nausea, vomiting, sore throat, loss of appetite and insomnia. The recommended dosage is 6 capsules, 3 times daily as long as required.

Patients with impaired immunity have found Ganoderma extract beneficial in boosting or modulating their immune system. The usual dosage is 4 capsules, 3 times daily. Patients could expect to see results in 1 to 2 months. Patients taking the extract for the first time can be subject to temporary symptoms, which are reflective of the efficacy of the nutriceutical in cleansing the body systems. These may include sleepiness, abnormal sweating, thirstiness, loose stool, frequent urination, bloating and possibly some rashes.

References

Chen, A., Miles, P. (1996). Biomedial research and the application of mushroom nutriceuticals from ganoderma lucidum mushroom biology and mushroom production: Proceedings of the 2nd international conference, June 9-12, 1996. University Park, PA: Pennsylvania State University: World Society for Mushroom Biology and Mushroom Products. P. 161-175.

Kimmons, T. (2003). Coauthor of effects of management on the yield and high-molecular-weight polysaccharide content of shiitake (Lentinula edodes) mushrooms. Personal Communication.

Soo, Teow Sun. (2004). Effective dosage of the extract of ganoderma lucidum in the treatment of various ailments . Mushworld. Retrieved July 28, 2004.

Reishi History

THE HISTORY OF REISHI Mushrooms by Dr. Howard W. Fisher

Humanity has been seeking to improve the quality of life since before the discovery of fire. Archaeological evidence indicates that mushrooms have been in useby man for more than 7000 years.(1) Many Oriental civilizations have realized the amazing health inducing benefits associated with certain mushrooms,(2) and yet in Western civilization they are relatively unknown. Sadly traditional medicine has adopted an anti- disease approach to health where killing the microorganism is the prime objective and hopefully this occurs before the host dies.

Reishi mushrooms have a history dating back over 4000 years when they were considered to be a 'superior herb that improved health, resistance, longevity, energy and memory. Asian rulers would sent out envoys to seek out old plum trees and there, growing out of the trunk on three out of every ten thousand trees, was the ganoderma lucidum, the reishi mushroom. The Japanese gave it the name Reishi or Mannetake meaning '10,000 year mushroom' and in China and Korea it is known as Ling Chu or Ling Zhi, the 'mushrooms of immortality' and 'the resurrection plant'(3). Many cultures embraced Reishi's benefits; the Romans considered mushrooms to be 'the food of the Gods', the Egyptians believed them to be 'a gift from Osiris' and the Chinese thought of them as 'the elixir of life'.

The benefits of Reishi mushrooms have been recorded throughout time, appearing in written documents as far back as the Han Dynasty (206B.C. - 8 A.D.). In these documents Reishi was associated with happiness, a good future, good health, longevity and living among the immortals. Reishi was so entrenched as a panacea in ancient Chinese culture that it is the focus of a Chinese fairy tale, "The White Snake." In this fairy tale the heroine, in an attempt to save her lover's life, tries to steal a Reishi plant from the Gods.(4)

The scientific community did not start to investigate the therapeutic properties of mushrooms until the late 1960s. One of the fundamental problems with Reishi research was that before the Japanese initiated commercial cultivation of the mushroom in the early 1970's, there was not enough standardized Reishi to conduct experimental evaluation of the properties. Fortunately, scientific research has discovered plentiful health benefits that corroborate the centuries of intrigue by ancient Asian royalty.

(1) Samorini G. New data on the ethnomycology of psychoactive mushrooms. International Journal of Medicinal Mushrooms. 2001; 3, 257-278.

(2) Hobbs C. Medicinal mushrooms: an exploitation of traditional healing and culture. Santa Cruz. Botanica Press. 1995.

(3) Shiao M S, Lee K R, Lin L J and Wang C T. Natural products and biological activities of the Chinese medical fungus, Ganoderma lucidum. In Ho C T, Osawa T, Huang M T and Rosen R T. Food phytochemicals for cancer prevention II: Teas, spices and herbs. American Chemical Society. Washington, D.C. 1994; p.342-354.

(4) Sing W S. Red Reishi. World Health Publishing Inc. Vancouver. 2003; p12.

Reishi History

History of Reishi

The virtues of Ling-Zhi (Reishi), are believed to have been known since Chinese great antiquity, since at least the reign of "Fuxi", a legendary ruler of that time known also as the first of the Three August Ones.

Seng Nong, the Holy farmer, who was the second of the Three August Ones, is said to have discovered the curative virtues of plants by tasting hundreds of species. "Seng Nong's Herbal Classic" is considered to be the earliest manuscript on Chinese materia medica and is still today the foundation of Traditional Chinese Medicine and in general all Oriental Medicine.

Seng Nong's Herbal Classic describes ling-zhi in detail: among 365 species of plants, roots, wood, fur, animals and stones, divided into 3 grades, Ling-zhi is listed No.1 among the first "superior" grade. The characteristic of the first grade is that no side effects occurs even being taken for a long period of time. On the contrary, longer taking reduces weight and extends life.

Six species of Ling-zhi, differentiated by colors, are mentioned in the Seng Nong classic. Li Shi Zhen, a famous medical scholar in the Ming Dynasty (1368-1644) introduced the indications of the 6 species concretely. The work of the latter was republished in 1956, and translated into several foreign languages including Japanese, English, French, German, Russian and Latin and is regarded as the cornerstone of Traditional Chinese medicine.

To find Ling-zhi in ancient times, people had to go high up on the mountains and deep into the forests to harvest this most valuable medicine. The discovery of Ling-zhi, which was very scarce, and which was believed to bring eternal longevity, led to wide spread festivities. Ling-zhi was so valued it was used almost exclusively by Emperors and by courtesans.

Preparation was a long process of boiling the mushrooms for hours or let them soak in alcohol for weeks so as to be able to drink them after its active ingredients have been dissolved.

Cultivation was attempted since ancient times in China but did not give satisfactory results both quality wise and quantity wise. It is only in 1971 that a Japanese researcher Yukio Naoi from the Kyoto University found ways to cultivate Ling-zhi or Reishi in quantity. Since the discovery of this method and with further amelioration, the production of Reishi raised more than 10 folds in the last ten years.

Today, an estimated 4,300 tons of Ling-zhi is produced yearly in the world, with China producing 3,000 tons followed by Korea, Taiwan, Japan, Thailand, USA, Malaysia, Vietnam, Indonesia and Sri Lanka.

Cultivation

Artificial cultivation of REISHI: To harvest high-quality Ganoderma lucidum

Yukio Naoi, Koujouen Co. Ltd.

In Japan, Ganoderma lucidum are grown using the following methods:

1) Wood log cultivation, the most popular method. 2) Pot or bottle cultivation. 3) Tank cultivation.

Over the past 30 years, a considerable number of studies have been made on the best method to harvest high-quality Ganoderma lucidum. These observations have shown that the best method to harvest high-quality Ganoderma lucidum is the wood log cultivation. Other particular conditions are necessary to get high-quality Ganoderma lucidum which we may consider under the following heads:

(l) Selection of the highest strain (2) Using the right method of cultivation (3) To harvest them at the right time (4) To treat them properly after the harvest

(1) Selection of the highest strain:

The term "strain of Ganoderma lucidum" is not defined academicaly. We use the term "strain of Ganoderma lucidum" here, to classify Ganoderma lucidum for being spread. There are many strains of Ganoderma lucidum, and Ganoderma lucidum included in the "GY system" are all of good strains. There are three typical strains "GYN", "GYK", "GYG" all part of the "GY system" Ganoderma lucidum. These strains have special characteristics as defined in the following table.

The biggest notable characteristics of these "GY system" Ganoderma lucidum is their effectiveness as a panacea. A "cure-all" medicine is not conceivable in modern medicine, but we believe that there are "cure-all" traditional medicine. The best account for it can be found in the followings:

1) Modern medicine : The efficacy of medicine understood and used for "scientific reason".

2) Traditional medicine : The efficacy of mind "Sei", "Ki", "Shin" (Energy, Air and Spirit) in food is understood and used by mystic sensitivity.

It also can be found in the descriptions of "Honzo Komoku"; the ancient Chinese book of medicine.

(2) Using the right method of cultivation

The medical efficacy of Ganoderma lucidum is distributed abundantly in hymenium.

From this view point I may say that Ganoderma lucidum, without hymenium, cannot be regarded as high-quality Ganoderma lucidum, even if it may have been the highest strain, grown in the good method, harvested at the good time and treated properly after the harvest.

To make good Ganoderma lucidum with abundant hymenium, there are some important points to follow:

1) To cultivate using wood logs; 2) To cultivate using "natural stimulations" (temperature, moisture, sunlight, wind and soil bacterium) as thoroughly as possible.

In few words, it is important not to grow them overprotectively.

(3) To harvest them at the right time

All life has only one "peak" during its lifetime when all its life forces: "Sei", "Ki" and "Shin" (Energy, Air and Spirit) are at their most powerful. It is at this time that its propagative powers becomes optimum. When cultivating Ganoderma lucidum, it is important to monitor and harvest at this particular time. We can underline that the possibility to harvest at this optimum time is one advantage of artificial cultivation of Ganoderma lucidum.

(4) To treat them properly after the harvest

Ganoderma lucidum makes "anti-disease power" when living (or anti-bodies to fight against bacteria, etc... from the soil) . It is this "anti-disease power" that we expect to act favorably when consumed. All life has healing properties that raise its own anti-disease power, under stern conditions of nature, and abiding by providence of nature.

Fresh cells of Ganoderma lucidum start to perish immediately after the harvest. Ganoderma lucidum must not be dehydrated rapidly artificialy as that hinders the growth of the anti-disease power.

Ganoderma lucidum can be preserved in cool, dark and stable place.

Research Studies

Role of Ganoderma Supplementation in Cancer Management

Raymond Y. Chang, Meridian medical Group at the Institute of East-West Medicine and Department of Medicine, Cornell Medical College

Ganoderma has been used as folk medicine since ancient times and it is a popular health food frequently promoted as a cancer cure. It is now well established from in vitro and animal studies that the polyshaccharide fraction of Ganoderma is largely responsible for its anti-tumor efficacy. Although there is yet no controlled clinical trials in humans for Ganoderma against cancer to date, the indications for its supplemental use can be indirectly supported with clinical trial data from comparable fungal polysaccharides because of a common final pathway of action mediated via beta-glucan receptor. Based on such indirect data, indications for Ganoderma use in cancer include supplementation a) to reduce side-effects during chemotherapy or radiotherapy, b) to prolonging survival and minimize metastasis, c) to improve quality of life, and d) to prevent occurrence or recurrence. In sum, although the cure

of any cancer with Ganoderma alone is unlikely, it is probably beneficial under defined circumstances in most cases of malignancy.

Introduction

Ganoderma has been recognized traditionally and scientifically as potentially useful in the treatment of cancer, but there is a notable discrepancy with the publics frequent impression that ganoderma may be a cure for cancer and the lack of clinical trials demonstrating such efficacy. We intend to summarize the extent of available theoretical, experimental and clinical data for the use of Ganoderma Supplementation in cancer and outline its indications, especially in the context of clinical results from bioactively similar polysaccharide derived biological response modifiers (BRMs) from other fungi (Mizuno 1996).

Experimental Evidence of Ganodermas Potential in Cancer Treatment

Ikekawa et al. (1968) first reported on the efficacy of soluble extracts from Ganoderma in inhibiting transplanted sarcoma 180 in mice. This host-dependent anti-tumor activity has been subsequently confirmed to be from the polysaccharide fractions of Ganoderma (Sasaki et al., 1971). Multiple similar studies subsequently confirms this observation and anti-tumor efficacy of Ganoderma has been demonstrated from various species, at different stages of growth and using different solvents for extraction and different routes of administration. Anti-tumor activity has been demonstrated in vitro as well as in syngeneic tumor systems in animals. However, no human trials of Ganoderma against cancer in peer reviewed journals nor any controlled clinical trials in humans have yet been conducted or published.

From a theoretical point of view, it is important to note that other fungal polysaccharides of comparable structure and function as those found in Ganoderma have undergone rigorous clinical trials, including Lentinan, Sizofilan, PSK (Krestin), PSP. Since it is now increasingly clear that immunostimulatory bioactivity from most beta-glucan based compounds function via a similar beta-glucan receptor (Czop 1985), it has been possible to hypothesize that Ganoderma polysaccharides should function similarly (Chang, 1996). Clinical effects of various glucan based BRMs should therefore be comparable. Results from Lentinan, Sizofilan, PSK and PSP human trials demonstrated the efficacy of these glucan BRMs in prolonging survival in recurrent or advanced gastric and colon cancer, lung cancer and gynecological cancers, Data from such bioactively comparable compounds all suggest improved quality of life or survival for cancer patients may be possible with Ganoderma supplementation.

Indications and Evidence Supporting the Use of Ganoderma Supplementation in Cancer

Whilst some efficacy of Ganoderma in cancer is undoubted, it remains important to specify the various indications and cite the evidence to support its use. This can be discussed under four different circumstances:

A. As a supplement during chemotherapy or radiotherapy to reduce side-effects such as fatigue, loss of appetite, hair loss, bone marrow suppression and risk of infection. There are studies demonstrating Ganodermas efficacy against fatigue (Yang 1994), hair loss (Miyamoto et al. 1985), and bone marrow suppression (Jia et al. 1993) and the presence of similar clinical evidence for other glucan BRMs applied in the setting of cancer chemotherapy or radiotherapy (Shi 1993) lends further support to the supplementation of Ganoderma in combination with cytotoxic cancer therapies. The recommended dose should be in the range of five to ten grams of fruiting body or equivalent per day (Chang 1994).

B. As a supplement for cancer patients to enhance survival and reduce likelihood of metastasis. While only anecdotal data exists that ganoderma supplementation may enhance survival of cancer patients, this survival advantage has been demonstrated for a number of

comparable glucan BRMs. Specifically, Lentinan use in advanced or recurrent gastric cancer demonstrated a significant life span prolongation advantage at 1, 2, 3 and 4 years in a randomized control trial (Taguchi 1987). Sizolan given together with chemotherapy enhanced survival of cervical cancers irrespective of stage in a prospective randomized controlled trial (Inoue et al. 1993), significantly enhanced survival (P.01) in lung cancer patients (Honma 1982) and improved five year survival of head and neck cancer from 73.4 to 86.7% was noted in another small study (Kimura et al. 1994). More appropriate for comparison to Ganoderma is perhaps PSK or PSP, which are orally administered. Mitomi et al. (1994) found significantly improved survival and disease-free survival (P=0.013) in resected colorectal cancer given PSK supplementation over three years when compared to control in a multi-center randomized controlled trial.

In an animal model, Ganoderma has been demonstrated to effectively prevent metastasis (Lee 1984), and these results are comparable to those of Lentinan (Suga 1994). Other glucan BRMs have been demonstrated to effectively prevent or suppress pulmonary metastasis of methylcholanthrene-induced sarcomas, human prostate cancer DU145M, and lymphatic metastasis of mouse leukemia P388 (Kobayashi et al. 1995). The recommended dose should be five to ten grams or more of fruiting body or equivalent per day, with a linear enhancement in efficacy expected up to 30 grams per day (Chang 1994).

C. As a supplement for cancer patients to improve quality of life. Again, only anecdotal information exists for Ganoderma in this situation but other oral glucan derivatives such as PSP has been found to be useful in improving quality of life in cancer patients (Yao 1993). Significantly, Ganoderma supplementation was noted to decrease pain in cancer patients (Kupin 1994). The recommended dose would be five to ten grams of fruiting body or equivalent per day (Chang 1994).

D. As a supplement for the prevention of occurrence or recurrence of cancer. Since immune stimulation, especially Natural Killer (NK) and Cytotoxic Lymphocyte (CTL) activation may be effective in the immune prevention of cancer by enhanced immune surveillance (Lotzova 1985), and Ganoderma has been demonstrated to enhance NK and CTL activity when administered orally (Won et al. 1989), it is thus a candidate for prevention of the occurrence or recurrence of cancer. Stavinoha et al. demonstrated the efficacy of Ganoderma in preventing the progression of microadenomatous growths in animals (Stavinoha 1993), and the efficacy of other glucan BRMs in primary and secondary cancer prevention have been similarly demonstrated in vitro, in vivo and in clinical trials.

Conclusion

Although Ganoderma and its derivatives are not pharmaceuticals and have not undergone rigorous clinical trials to be tested against cancer, there is abundant use in vitro, animal and indirect clinical evidence to support its supplemental use in cancer. Standardization in bioactive polysaccharide content and dosages will be necessary to assure its rational use, and clinical trials in select cancers with defined endpoints will confirm its efficacy.

References

- Chang, R. (1994). Effective dose of ganoderma in humans. In Proc. Contributed Symposium 59A, B. 5th Intl. Mycol. Congr., Buchanan PK, Hseu RS and Moncalvo JM (eds), Taipei, p. 101-13. - Chang, R. (1996). The Central Importance of the beta-glucan receptor as the basis of immunologic bioactivity of ganoderma polysaccharides, In Reishi, Mizuno T, Kim BK (eds), II Yang Press, Seoul, p.177-9 - Chang, R. (1996). Potential application of ganoderma polysaccharides in the immunosurveillance and chemoprevention of cancer. In Mushroom Biology and Mushroom Products, Proceedings of the 2nd International Conference, Royse DJ (ed), Penn State U. Press, University Park, p.153-9

- Czop, J.K., Austen, K.F. (1985). A beta-Glucan inhibit able receptor on human monocytes, J. Immunol. 134, 2588-593. - Honma, H., Oshima, S., Watanabe, S. et al. (1982). Clinical efficacy of schizophyllan (SPG) in treatment of lung cancers. A Randomized controlled study. Haigan 22: 499-512. - Ikekawa, T., Nakanishi, M, Uehara, N., et al. (1968). Anti-tumor action of some basidiomycetes, especially Phellinus linteus. Gann. 59* 155-157. - Inoue, M., Tanaka, Y., Sugita, N., et al. (1993). Improvement of long-term prognosis in patients with ovarian cancers by adjutant sizofilan immunotherapy: a prospective randomized controlled study. Biotherapy. 6(1): 13-8 - Jia, YF., Zhou, XB., Meng, H., and Zhang, LX. Effects of Ling-Zhi on hemopoietic system in mice - immunopharmacological study (11). In The research on ganoderma (part I). Zhu S. and Mori M. (eds). Shanghai Med. U. Press, Shanghai, P. 284-288. - Kimura, Y., Tojima, H., Fukase, S., Takeda, K. (1994). Clinical evaluation of sizofilan as assistant immunotherapy in treatment of head and neck cancer. Acta Oto-Laryngologica - Suppl. 511:92-5 - Kobayashi, H., Matsunaga, K., Oguchi, Y. (1995) Antimetastatis effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer Epidemiology, Biomarkers & Prevention. 4(3): 275-81 - Kupin, V. (1994) A new biological response modifier - ganoderma lucidum - and its application in oncology. In Proceedings from the 6th international symposium on ganoderma lucidum. Seoul, II Yang, p.36-37. - Lee, SS., Chen, FD., Chang, SC., et al. (1984). In vivo anti-tumor effects of crude extracts from the mycelium of ganoderma lucidum. J. of Chinese Oncology Society 5(3): 22-28. - Mitomi, T., Tsuchiya, S., Iijima, N., et al. (1992). Randomized control study on adjuvent immunochemotherapy with PSK in curatively resected colorectal cancer. Diseases of the Colon & Rectum. 35(2):123-30. - Miyamoto, T., Abe, T., Hasunuma, K. (1985). Japan Kokai Tokkyo Koho JP60, 199,80 [85,199.810] (CI. A61K7/06). Appl. 84/5,977. 24 Mar 1984. - Mizuno, T. (1996), A development on anti tumor polysaccharides from mushroom fungi. FFI Journal, 167:69-85. - Shi, JH. (1993). PSP for the protection of the tumorous patients during chemotherapy. In 1993 PSP Intl Symposium, Yang QY and Kwok CY (eds.), Fudan U. Press, Shanghai, p.271-2 - Stavinoha, W. (1993). Short term dietary supplementation with ganoderma lucidum slows development and growth of microadenomatous lesions in the colon of rats treated with the carcinogen 1,2 dimethylhydrazine. Presented at the 5th international symposium on ganoderma lucidum, Seoul, Korea on June 17, 1993. - Suga, T., Shiio, T., Maeda, YY., Chihara, G. (1994). Anti tumor activity of lenytinan in murine syngeneic and autochthonous hosts and its suppressive effect on 3 methylcholanthrene induced carcinogenesis. Cancer Res. 44:5132-7. - Taguchi, T.(1987). Clinical efficacy of lentinan on patients with stomach cancer: end point results of four-year follow-up survey. Cancer Detection & Prevention. Suppl. 1:333-49. - Won, SJ., Lee, SS., Ke, YH., Lin, MT. (1989) Enhancement of splenic NK cytotoxic activity by the extracts of ganoderma lucidum mycelium in mice. J Biomed Lab Sci 2*201-213. - Yang, QY and Wang, MM. (1995). The effect of ganoderma lucidum extract against fatigue and endurance in the absence of oxygen. In Proc. Contributed. Symposium. 59A, B.2. Role of Ganoderma Supplementation in Cancer Management

Research Studies

Status of Ganoderma Lucidum in United States: Ganoderma Lucidum as an Anti-inflammatory Agent

William B. Stavinoha, University of Texas Health Science Center San Antonio

Neera Satsangi, University of Texas Health Science Center, San Antonio, Texas 78284-7764, USA

The status of herbs has recently changed in the United States with the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). This law created a new category called Dietary Supplements which includes herbs. The act declares these substances are not food additives nor are they drugs. It allows manufactures to publish more complete directions for use than previously allowed including warnings, contraindications, and side effects. The act also allows manufacturers to publish limited information regarding the benefits in the form of Statements of Nutritional Support as well as Structure and Function Claims.

Alzheimers Disease is primarily an old age disorder in which competent individuals become agitated, uncomprehending, with profound loss of cognitive function finally requiring continued and complete care. In the United States it is the fourth leading cause of death. At present, the choice of therapeutic or preventive drugs for use in Alzheimers disease is limited and the best only slow the progress of the disease for about 40 weeks. Recent research has discovered evidence of inflammation in the brain of Alzheimers patients and unless inflammation is present there is little evidence of neurodegeneration, even in patients with profuse amyloid B-peptide deposition and neurofibrillary tangles. Prospective and retrospectively collected data on men and women suggest that use of non steroidal antiinflammatory drugs is associated with reduced risk of Alzheimers disease. This research heightens the importance of the ancient reports where Ganoderma lucidum was praised for its effect of increasing memory and preventing forgetfulness in old age reported in Shen Nong Ben Cao Jing vol. 1 as early as 456-536 AD. Research on mice using orally or topically administered Ganoderma lucidum provides evidence that Ganoderma lucidum has anti-inflammatory activity. This pharmacological activity may provide the basis for its activity on memory in old age, although we do not know as yet that Ganoderma lucidum can enter the brain and exert antiinflammatory activity. In cardiovascular research, it has been found that aspirin ingestion can reduce the incidence of cardiovascular disease. The possibility that it is antiinflammatory activity of aspirin that can provide benefit in reducing the risk of cardiovascular disease is suggested by the finding that higher levels of C-reactive protein in the plasma which is an acute phase marker for systemic inflammation is a predictor for increased risk of cardiovascular disease. These studies on inflammation provide important

evidence that warrants further study of Ganoderma lucidum and its possible role in mitigating these two devastating diseases.

Another important event more specific for Ganoderma was the incorporation of the Ganoderma International Research Institute in New York in 1993 for the purpose of fostering international scientific and medical research on Ganoderma, setting standards of quality for related products and to promote popular awareness and appropriate use of Ganoderma.

Research on Ganoderma in the United States is not extensive. The major reason is the lack of research funds available. The interest of the public in herbal medicine is growing, the sales of herbal products is increasing yearly, with little effect on research funding.

Ecological studies along the Savannah river in South Carolina by Chen et al., (1993) identified Ganoderma as the first long-spore species in the genus to associate with oak. More recently Chenand Hu (1994) reported three successful strategies for obtaining monokaryons in Ganoderma species. To my knowledge the major producer of fruiting body Ganoderma lucidum in the United States at present is Organotech of San Antonio.

In clinical studies Chang (1994) at Sloan-Kettering Cancer Center reported that applications of Ganoderma should be studied and considered for (1) chemoprophylaxis of cancer in individuals at high risk for developing cancer (2) adjuvent use in the prevention of metastasis or recurrence of cancer (3) palliation of cancer related cachexia and pain and (4) adjunctive use with concurrent chemotherapy to reduce side-effects, maintain leukocyte counts and allow a more optimal dosing of chemo or radio therapeutics. In a very interesting report Chang (1993) addressed the question of proper dose of Ganoderma for therapy. Since studies of human dosage were traditional and empiric a dose range was calculated using this data and pharmacokinetic principals. The calculations suggested that a (1) Ganoderma dried fruit body dose of 0.5 to 1 g per day for health maintenance (2) 2 to 5 g per day if there is chronic fatigue, stress, auto immune, or other chronic health problems (3) 5 to 10 g per day for serious illness.

Of great interest has been the recent reports from the United States indicating a possible central role for inflammation in the development of such diverse diseases as Alzheimers Disease and Cardiovascular disease. This research has the possibility of linking some of the historical uses of Ganoderma in promoting longevity with contemporary Western scientific theory. The provocative connections are: (1) Ganoderma was used to prevent memory loss in old age (2) Ganoderma is anti-inflammatory, (3) inflammation is involved in the development of Alzheimers disease (4) Alzheimers disease appears to be ameliorated by chronic antiinflammatory use.

(1) Ganoderma and old age: The ancient Chinese text Shen Nong Ben Jing volume 1 from about the year 500 states that Ganoderma lucidum is useful for enhancing vital energy, increasing thinking faculty and preventing forgetfulness. It can refresh the body and mind, delay aging and enable one to live long. It stabilizes ones mental condition (Mizuno 1996). The importance of retaining memory into old age probably lies in the Taoist belief that sickness was caused by past transgressions and that the patient had to remember the transgressions, record them and destroy the record. This belief placed a strong emphasis on memory in the maintenance of health and longevity.

(2) Antiinflammatory: In research in mice Stavinovah et al. (1991, 1996) found Ganoderma lucidum to be potent antiinflammatory agent. The water extract of the fruiting body was active orally against both carrageenan induced inflammation and croton oil induced inflammation. The ethyl acetate extract was active as an antiinflammatory agent both orally and topically. The active compound was isolated and identified. This compound is equivalent in antiinflammatory activity to hydrocortisone. It does not show the typical side effects of steroids such as thymic involution nor appear to cause gastropathy which is the major side effect of the non-steroidal antiinflammatory drugs such as aspirin.

(3) Inflammation and Alzheimers disease: A number of indicators of active inflammation have been found in the Alzheimers diseased brain. Unless inflammation is present there is no notable neurodegeneration or Alzheimers signs and symptoms even in the presence of extensive neurofibrillary tangles and Amyloid B-peptide plaque deposition (Rogers 1995).

(4) Nonsteroidal antiinflammatory drugs in Alzheimers disease: Researchers in the United States and Canada have found that ingestion of non steroidal antiinflammatory drugs can slow the progress of the disease (McGeer and Rogers 1992). In a report by Corrida et al. (1996) reported on findings on 1417 man and 648 women from Baltimore Longitudinal Study of aging which is 37 year multidisciplinary study of normal aging. The preliminary results suggest that use of nonsteroidal antiinflammatory drugs is associated with decreased incidence of Alzheimers disease.

In studying incidence of cardiovascular disease, Ricker et al. (1997) measures C-reactive protein, an acute phase reactant used as a marker for systemic inflammation, in plasma. They found that baseline plasma concentration of C-reactive protein predicts the risk of future myocardial infarction and stroke. The reduction of risk associated with aspirin appears to be directly related to the level of C-reactive protein, suggesting that antiinflammatory agents may have benefits in preventing cardiovascular disease. The increase risk was independent of lipid related and non-lipid related cardiovascular factors. Masari (1997) felt that the time has come to reexamine that pathogenetic components of these disease to identify patients who would benefit from particular therapies.

Considering these recent findings, research on Ganoderma as a potential useful antiinflammatory for a long term use as a prevention of disease appears warranted.

References

- Bass, L&Young, A. (1996). The Dietary Supplement Health and Education Act: A Legislative History and Analysis Washington D.C. Food and Drug Law Institute.

- Chang, R (1994) Effective Dose of Ganoderma in Humans; Proceedings of Contributed Symposium 59A, B 5th International Mycological Congress, Vancouver: pp. 117-121

- Chang, R (1993) Limitations and Potential applications of Ganoderma and related fungal polyglycans in clinical ontology; First International Conference on Mushroom Biology and Mushroom products: 96

- Chen, A. W., McLeod, K.W., Workman, S.W., Moran, M.A. (1993) Ecological Studies of a long-spores Ganoderma species from the Savannah river site, South Carolina; First International Conference on Mushroom Biology and Mushroom products: 103

- Corrada, M., Stewart, W., & Kawas, C. (1996). Nonsteroidal anti-inflammatory drugs and the risk of Alzheimers disease. Neurology, 46, A433.

- Maseri, A. (1997) Inflammation, atherosclerosis, and ischemic events-exploring the hidden side of the moon. New England J Medicine, 336 (14) 1014-1015

- McGeer, P., & Rogers, J. (1992) Anti-inflammatory agents as a therapeutic approach to Alzheimers disease. Neurology, 42, 447-449.

- Mizuno, T. (1996). Oriental Medicinal tradition of Ganoderma lucidum (Reishi) in China. In T. Mizuno & B. -K. Kim (Eds.), Ganoderma lucidum (pp.101-106). Seoul, Korea: II-Yang Pharm. Co. Ltd.

- Ridker, P.M, Cushman, M., Stampfer, M. J., Tracy, R.P. and Hennekens, C.H. (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New England J. Medicine, 336 (14) 973-979

- Rogers, J. (1995). Inflammation as a pathogenic mechanism in Alzheimers disease. Arzheim. -Forsch., 45, 439-442

- Stavinoha, W., Satsangi, N., & Weintraub, S. (1995). Study of the antiinflammatory efficacy of Ganoderma lucidum. In B.-K. Kim, & Y.S. Kim (Eds.), Recent Advances in Ganoderma lucidum research (pp. 3-7). Seoul Korea: The Pharmaceutical Society of Korea. Stavinoha, W., Slana, J., Weintraub, S., & Mobley, P. (1991). The Antiinflammatory activity of Ganoderma lucidum. Third International Symposium on Ganoderma lucidum, 9-21

Research Studies

Cultivation, Utilization, and Medicinal Effects of Ganoderma Lucidum in Malaysia

Teow Sun-Soo, Department of Microbiology & Biochemistry, School of Applied Sciences, MARA Institute of.Technology, Malaysia

Abstract: In Malaysia, Ganoderma lucidum was initially cultivated in the 1980'5. More recently, hybrid cultures of G. lucidum were used for mass production which only required 40 to 45 days of incubation. The basidiocarps are sliced and brewed as a tonic or as Ganoderma tea. They may also be powdered or extracted with solvent to yield the finished product which is then made into capsules. Ganoderma nutriceuticals are used as a remedy to treat more than 20 different illnesses which include migraine and headache, hypertension, arthritis, bronchitis, asthma, anorexia, gastritis, haemorrhoids, hypercholesterolaemia, nephritis, dysmenorrhoea, constipation, lupus erythematosis, hepatitis, leukopenia, cardiovascular problems and cancer including leukaemia.

Introduction

Ganoderma lucidum was acclaimed as a divine herb that could bestow longevity. It was also deemed as an elixir of life that it could augment good health and well- being. This might be the case when certain mushrooms were treated as objects of worship or as objects of mysteries describing them as celestial herbs possessing panaceal properties. Nowadays, modern research has revealed its active ingredients, which include polysaccharides, organic germanium, triterpenoids, adenosine, LZ-8, and an array of amino acids besides numerous mineral types.

Cultivation of Ganodema Lucidum in Malaysia

Cultivation of G. lucidum in Malaysia was initially attempted by Teow in 1984') using sawdust in polypropylene or polyethylene bags in sheds under palm oil trees. Subsequently, better hybrids were obtained through cross-breed-lug which only required 40 to 45 days of incubation2). for its cultivation. The annual production of the basidiocarps of G. lucidum in Malaysia is estimated to be around 300 tons but the production of mycelium is negligible.

Utilization of Ganodema Lucidum

The basidiocarps are sliced and brewed and are taken as a tonic or Ganoderma tea. It may also be powdered or extracted with chemical solvent and the finished pro-duct is then processed into capsules.

Medicinal Effects of Ganoderma Lucidum

The beneficial medicinal effects of G. lucidum may be summarized as follows:

Effect on Hepatitis B

G. lucidum has been shown to be effective in the treatment of Hepatitis B resulting in the lowering of SGPT and SCOT levels to normal, and the sero-conversion of HBs antigen to HE, antibody3). Extract of G. lucidum when administered concurrently with glutathione against liver damage by car- bon tetrachloride, proved to be beneficial against hepatic necrosis and hepatitis4). It was also discovered that extract of G. lucidum could probably augment the rate of toxin transformation and subsequent bile excretion, thereby acting as a liver detoxicant and protectant5).

Effect on Diabetes

Extract of G. lucidum has also been found to be effective in reducing the blood glucose level after two months of treatments). Ganoderan B was considered to enhance glucose utilization because it increased the plasma insulin level in normal and glucose loaded mice, but did not affect the insulin binding to isolated adipocytes6). The hypoglycaemic activity of G. lucidum is thus due to an increase of the plasma insulin level and an acceleration of glucose metabolism occurring not only in the peripheral tissues but also in the liver.

Effect on Hypertension

G. lucidum is also effective in lowering hypertensive blood pressure. This is due to the presence of lanostane derivatives especially ganoderic acids B, D, F, H, K, S and Y which exert their hypotensive activities 7).

Effect on Acute Myeloblastic Leukaemia

Acute myeloblastic leukaemic patients were treated with high doses of G. lucidum (6 capsules 3 times a day) prior to chemotherapy and continued for a period of three months. The chemotherapy regimen consisting of cytarabine and daunorubicin was given on a monthly basis in order to induce remission. CNS prophylaxis was given with cranial irradiation. All the patients had a subjective response when G. lucidum was included in their treatment regimen. Changes in their NBC, hemoglobin and platelet counts were either significant or very significant after 3 months of treatment. Despite the remission for the past 3 years, the long term prognosis seems encouraging.

Effect on Nasopharyngeal Carcinoma

Five patients with stage III nasopharyngeal carcinoma (NPC) were given 6 capsules of G. lucidum 3 times a day for 1 week before radio-and chemotherapy and continued for a course of 8 months while they were given a complete course of irradiation lasting for 6 weeks. The chemotherapy regimen consisting of cyclophosphomide, lomustine, dannorubicin and vincristine was administered every month for a period of 4 months. Objective response occurred in all the NPC patients with very significant tumor shrinkage after 40 days of treatment with G. lucidum in concurrence with radio- and chemotherapy. The tumors were completely regressed after 90 days of combined treatment and were in remission for the last three and a half years. It is conceivable that G. lucidum plays an adjuvant role in combination with radio- and chemotherapy, thereby rendering the complete regression of the tumors.

Since both polysaccharides' and organic germanium derived from G. lucidum are not cytotoxic to tumor cells, the antitumor effect is attributable to induced immunopotentiation. As an immunopotentiator, G lucidum accelerates the production of interlukin-2 from helper T cells and potentiates the induction of different types of anti-tumor cells, such as NK cells and cytotoxic macrophages, in addition to the induction of interferon production. The patients felt more energetic, and had a better appetite and slept better. Nausea and vomiting were mild whereas stomatitis and sore throat were transient. Their pain was alleviated, and no other side effects were observed.

Effect on Wound Healing

Three patients with diabetic wounds were healed between 15 to 22 days. This might be due to the glucan from the cell walls of G. lucidum that could activate the fibroblast migration in order to achieve wound healing and tissue proliferation. Considering all these effective findings, further research on G. lucidum as a potential nutriceutical for similar illnesses or other ailments seems warranted.

References

1. Teow, S. S. l986. Cultivation of Ganoderma lucidum and its medicinal value. In extended Abstract. 9th Malaysian Microbiology Symposium, 79-82.

2. Teow, S. S. 1994. Ganoderma lucidum in 40 days. In Abstract. '94 International Symposium on Ganoderma Research. P 21.

3. Teow, S .S. 1997. The effective application of Ganoderma nutriceuticals. In B.K. Kim, C.K. Moon, and T.S. Kim (Eds), Recent Progress in Ganoderma lucidum Research (pp. 21-39) Seoul, Korea. The Pharmaceutical Society of Korea.

4. Byun, S. H. & Rim I.H. 1987. Studies on the concur rent administration of Ganoderma lucidum extract and glutathione on liver damage induced by carbon tetrachloride in rats. J. Pharm.. Boo. Korea, 31:133-139.

5. Liu, G. Ban, T., Niu, X., Li, S. & Sung, Z.1979. Some pharmacological actions of the spores of Ganoderma lucidum and the mycelium of Ganoderma capense cultivated by submerged fermentation. Chinese Med. J. 92:496-600.

6. Hikino, H. Ishiyama, M., Suzuki, Y. & Kono, C. 1989. Mechanism of hypoglycemic activity of Ganoderma B: A glycan of Ganoderma lucidum fruit bodies. Plants Medica, 55:423-428.

7. Morigiwa, A.) Kitabatake, K., Fujimoto, Y. & Ikekawa 1986. Angiotensin converting enzyme-inhibiting triterpenes from Ganoderma lucidum. Chem. Phar. Bull. 34:3025-8028.

Research Studies

Studies on Bioactive Substances and Medical Effects of REISHI, (Ganoderma Lucidum)

Takashi Mizuno, Shizuoka University, Japan

Reishi, the fruiting body of Mannentake, Ganoderma lucidum has been known in Japan, China, and other countries as a food and raw material for the development of drugs. recent studies have shown that that carcinostatic substance in Reishi is a polysaccharide, beta (1-3)- D - glucan. This polysaccharide seems to have promise as a new type of carcinostatic agent which might be useful in immunotherapy. Unlike chemicals used in chemotherapy, it has few toxic side effects because its effect is based on immunological enhancement in the host. Reishi also seems to contain other substances which reduce blood pressure, blood cholesterol, and blood sugar levels; and inhibit platelet aggregation, etc.

Recently, in vitro immunomodulating effects of Reishi extracts, and clinical study of micronized Reishi in Thai HIV and AIDS patients were attempted in Thailand. Some lanostane tri-terpenoids have been isolated from G. lucidum. These are highly oxidized compounds which show interesting biological activities.

1. Artificial Cultivation of Reishi

Artificial culture and cultivation of Mannentake, G. lucidum fungus were attempted initially by T. Henmi et al., in 1937. Its mass production was first achieved by Y. Naoi in 1971 by cultivating the spawn using pots containing sawdust. Since then use of bed logs or sawdust has become established practice. For some purposes a bagasse spawn bed method and bottle or bag cultivation may be used. Usually, for mass cultivation of high quality Reishi, either outdoors, bed logs of white oak, oak, Japanese chest-nut, Japanese apricot, etc., are used.

The 1995 production of Reishi in Japan was estimated to about 500 tons dry weight. Reishi cultivation has also prospered in China, Taiwan, Korea, Thailand and Vietnam. In addition, attempts are being made to obtain useful cellular materials or to produce effective substances from cultures mycelia.

2. Pharmacologically Active Components in reishi

2.1 General Chemical Components in Reishi

The major components and the free amino acids in Mannentake fruiting body (reishi) have been determines. Both qualitative and quantitative differences are found in the composition of naturally grown and artificially cultivated sampled of reishi, depending on the lines, places of the production, cultivation conditions, etc.

2.2. Medicinal Effects of reishi Extract with Hot Water

The hot water extract (ca. 10% dry matter) obtained from Reishi seems to have some properties. Little could be done to isolate the pure substances having these medicinal properties until recently, when the culture and cultivation of Mannentake became possible.

The results of this research are described below. Anti tumor substances whose properties have been studied in depth are described in detail in the article Anti tumor-Active Substances from Mushrooms.

2.3 Bitter Terpenoids

The fruiting body of Mannentake (Reishi) is extremely bitter, a characteristic not found in any other mushroom. The bitterness varies in degree depending on the place of production, cultivation conditions, its strain, etc. This bitterness is not found in cultures mycelia or substances produced in the culture medium, and Kokushi (black Reishi) does not contain the bitter substance. Though the relationship between bitterness and pharmacological effects is not fully understood, the bitterness serves as a marker for pharmacological evaluation and classification of Ganoderma sp.

The bitter components and related compounds, highly oxidized lanostane triterpenoids isolated from Mannentake have been studied for their anti allergy action, etc.

2.4 Steroids

Ergosterol (pro vitamin D2) has been reported in concentrations of 0.3-0.4% in Reishi. However, further analysis has confirmed that the main component of the steroids is 24-methylcholesta-7, 22-dien-3-beta-ol. Ergosterol and 24-methylchesta-7-en-3-beta-ol are sub components. Recently, ganodesterone has also been isolated.

2.5. Nucleosides and Nucleotides

Like other mushrooms, reishi contains adenosine, 5-GMP, 5XMP, RNA, etc., components which contribute to umami. It has recently been found that nucleosides which contain adenosine and

guanosine, found in the water/alcohol extract of Reishi, possess a platelet aggregation action (antithrotic activity).

2.6. Hypoglycemic Glycans and Proteoglycans.

High hypoglycemic activity both in normal mice and in alloxan-induced hyperglycemic mice has been induced by two polysaccharide-protein complexes, Ganoderans B and C, by their i.p. administration to male mice of Std:ddY strain. These complexes were obtained by adding ethanol to a hot water extract of Reishi and separating the precipitated polymer substances by column chromatography. We have isolated, from Reishi fractions of water-soluble polysaccharides, a 3% ammonium-oxalate-soluble heteropolysaccharide, and 5% NaOH-soluble peptidoglycan. These were further separated into several fractions by various chromatographic methods. Strong anti tumor activity and hypoglycemic activity were found in certain fractions of the heteropolysaccharides.

No correlation was found between the anti tumor activity of these active peptidoglycans and their antihyperpgycemic activity or between the ratio composition of polysaccharides and proteins in the complex. Further research is needed to determine the source of these two activities.

2.7 Blood Pressure Stabilizing Components

Reishi has been assumed to have both hypotensive and hypertensive properties (homeostasis). A peptidoglycan (molecular weight, 100,000) having a mild hypotensive effect on Wister rats and SHR rats (congenitally hypertensive) has been isolated from hot water extract of reishi. According to one report, the blood pressure of about half the patients with hypertension was reduced when a Reishi extract was administered. it has been reported that a hypertension-related angiotensin-I-converting enzyme was inhibited by ganoderic acids (B, D, F, H, R, S, and Y), ganoderal A, and ganoderol A and B.

2.8 Antithrombotic Compounds (Platelet Aggregation Inhibitors)

Some active compounds have been isolated from mushrooms as platelet aggregation inhibitor. We have also isolated and identified adenosin, guanosin, and their derivatives as potent inhibitors from 80% ethanol extract Reishi. A novel substance showing a higher activity than those of the nucleotides was also obtained. Its structure has been identified as both epimers of 5-deoxy-5-methylsulphinyl adenosine.

2.9 Lectins

Investigation of lectins from G. lucidum are now being carried out at our laboratory. We have isolated lectins from the fruiting body and mycelium of this fungus. This myceliumlectin is the first isolated from other than the fruiting body of higher fungi.

3. Anti tumor Substances in Reishi

Mannentake (fruiting body and mycelium of G. lucidum fungus) contains various low molecular weight components. Free monosaccharides, sugar alcohols, oligosaccharrides, amino acids, organic acids, steroids, lipids, terpenoids, coumarin, tannin substances, etc., are among low molecular weight components extracted with various solvents of water/alcohol-water/acetone-water, etc.

3.1. Cytotoxic Terpenoids

It has been reported that some triterpenoids (ganoderic acid -R, -T, -U, -V, -W, -X, -Y, and -Z) isolated from cultures mycelia of G. lucidum, Mannentake showed a cytotoxicity-based carcinostatic effect on hepatoma cells in vitro.

3.2 Anti tumor Polysaccharides

Among polymer components in Reishi, many polysaccharides and their protein-complexes were extracted using hot water, ammonium oxalate solution, alkali solution, dimethyl sulfoxide (DMSO) solution, etc., and separated by various chromatographic methods.

These polysaccharide fraction were used for the screening of host-mediated Anti-tumor activities (BRM substances and immunotherapeutic agents) using Sarcoma 180 180/mice, i.p. or p.o. method. Strong anti-tumor activities were found in various hetero-beta-D-glycans having a beta(1-3)-D-glucan chain as the active site, such as beta-D-glucan, glucurono-beta-D-glucan, arabinoxylo-beta-D-glucan, xylo-beta-D-glucan, manno-beta-D-glucan and xylomanno-beta-D-glucan, as well as their protein complexes. These polysaccharides, especially in Reishi, will be examined for their possible use as new anti tumor agents.

In addition, polysaccharides having immunomodulated anti tumor activities or anti-inflammatory functions are contained not only in water soluble beta-D-glucans but also in hemicellulose (the so-called dietary fiber), which is water-insoluble. The polysaccharides present in hemicellulose can be extracted with alkali or DMSO in high yield.

In addition to these active polysaccharides, many other polysaccharides have been isolated or reported to exist, such as alpha-(1-6); alpha(1-4)-G-glucan (glycogen-like polysaccharide), fucogalactan, mannofucagalactan, fucoxylomannan and xylomannoarabinogalactan. None of these showed anti tumor activity.

3.3 Dietary Fibers

A high molecular component neither digested nor absorbed but excreted upon intake by human being is called the dietary fiber. Mushroom fungi contain dietary fibers belonging to beta-glucan, chitinus substances, hetero-polysaccharides (pectinous substances, hemicellulose, polyuronides, etc.) and others, as much as 10-50% in the dried matter.

Since beta-D-glucan and chitinous substance with carcinostatic activity are contained much in the dietary fiber of mushroom fungi, certain pharmacological effects can be expected, and further by physical actions, they absorb hazardous matters as carcinogenic substances to prevent their absorption in the intestine and to hasten their excretion (laxative action), thus it seems to work effectively to prevent cancer of the colon and rectus.

3.4 Germanium Components

Crude drugs obtained from ginseng, a polyporaceae, treasured as Oriental medicine have high germanium contents. The ability to concentrate Ge was confirmed in G. lucidum fungus. Correlation between the anti tumor activity (interferon-inducing activity) and Ge contents is also of interest because Ge is said to neutralize pain during the final stages of cancer.

4. Extracellular Polysaccharides of G. lucidum

Polysaccharides were produced extracellularly when G. lucidum mycelia were shaking cultured using a liquid medium containing monosaccharides or disaccharides as the carbon source.

Dried polysaccharides thus obtained were separated into water-insoluble (47%) and insoluble (53%) fractions. The water-insoluble polysaccharide fraction contained a beta (1-3)-D-glucan

having beta-(1-6) branches. When this glucan was administered to mice (10 mg/kgX10, i.p.), it showed high anti tumor activity, with the suppression ratio percentage of tumor proliferation being 92% and the complete regression ratio being 4/6. The water-soluble fraction contained a heteroglucan composed of glucose, mannose and galactose having no anti tumor activity.

5. Clinical Study and Immunomodulating Effects of G. lucidum Mushroom in AIDS and HIV Patients.

5.1. In Vitro Immunomodulating Effects of Reishi Extracts

Our preliminary in vitro studies indicated that certain extracts of Reishi may function as immunorestorer in mild to moderately immunosupressed individuals. The effect may be mediated through changes T cells phenotypes or through enhancement of T cell function. Therefore, proper selection of the patients to be tested is essential to guarantee the favorable outcome of the clinical study.

5.2. Clinical Study of Micronized reishi Mushroom in Thai HIV Patients.

A fine-powdered Reishi from Japanese G. lucidum mushroom was administered to ten patients with advanced HIV infection in Thailand. Only one patient had already taken antiretrovirals for two or more months before enrolling into the study and the CD4 count still remained under 200 cell/cu mm. The same antiretroviral regiments were maintained throughout the 12-week study period. Patients were observed every 4 weeks for clinical, CD4 and HIV viral load changes. Results indicated that micronized Reishi mushroom was well tolerated. Nevertheless, the product did not show any appreciable benefits either for the clinical symptoms, the CD4 counts or HIV viral loads.

Therefore, it is desired to purify the active ingredients from the mushroom such as the terpenoids and polysaccharides including beta-D-glucan and its protein complex before additional clinical test in HIV patients is warranted.

References

1) T. Mizuno: Anti tumor Active Substances of Mushroom Fungi, Based Science and Latest Technology on Mushroom, pp. 121-135 (1991), Nohson Bunka Sha, Tokyo 2) T. Mizuno: Chemistry and Biochemistry of Mushrooms, pp. 35-45, 211-221 (1992), Gakkai Shuppan Center, Tokyo 3) T. Mizuno: Reishi Mushroom, Recent Development of Physiologically Functional Food, pp. 319-330 (1996), CMC Co. Ltd., Tokyo. 4) T. Mizuno: Food Function and Medicinal Effects of Mushroom Fungi, pp. 1-170 (1994), Laboratory of Biochemistry, Faculty of Agriculture, Shizuoka University, Shizuoka. 5) T. Mizuno: Mushroom Science and Biotechnology, 1, 53-59 (1994) 6) T. Mizuno: Mushroom Science and Biotechnology, , 99-114 (1995) 7) T. Mizuno: Food and Food Ingredients Journal of Japan, No. 167, 69-85 (1996). 8) T. Mizuno: Food Reviews International, 11, 7-21, 23-61, 151-166 (1995). 9) T. Mizuno: Ganoderma lucidum, p. 253-279 (1996), IL-YANG Pharm. Co. Ltd., Seoul, Korea. 10) T. Mizuno: Mushroom Book No. 1, p. 60-65, p 106-112 (1995), Toyo Igakusha, Tokyo 11) T. Mizuno: Reishi book No. 1, p.88-92, p. 106-122 (1995), Toyo Igaku, Tokyo. 12) T. Mizuno: Unpublished data.