Medicinal Mushrooms

Modern Uses of Medicinal Fungi

Far from being curiosities of the past, medicinal mushrooms are gaining an ever-wider popularity today. This new interest has been greatly stimulated by the large number of scientific studies that have been conducted on medicinal mushrooms. These modern studies have confirmed the traditional uses of many fungi and have even found new applications for them in some cases. Let’s take a brief look at some of the findings. For complete summaries, see the monographs on individual species in the materia medica section.

Scientific Findings with Medicinal Fungi

One of the key results that has come out of both laboratory and human clinical studies conducted on fungi is that a number of compounds in fungi can stimulate immune function and inhibit tumor growth. In particular, compounds called polysaccharides, which are large, complex branched chain-like molecules built from many smaller units of sugar molecules, have been intensively studied since the 1950s. Again and again they have been shown to have antitumor and immunostimulating properties, not only from many of the medicinal mushrooms reviewed in this book, but also from lichens (such as usnea), bacteria, and even from the cell wall of a yeast (called zymosan) (Chihara et al, 1970b).

mannose
galactose
xylose
fucose
+18-38% protein co-valently bound
Fig. 7: High-molecular weight heteropolysaccharides

Recently, German researchers have demonstrated that immune-activating polysaccharides similar to those found in many fungi are also found in higher plants, such as the widely popular Echinacea, and Astragalus, an important Chinese herb (Wagner and Proksch, 1985). These giant molecules are similar to ones found in the cellular membranes of bacteria, and thus may “fool” our immune system into mounting an immune response to them, while posing no actual threat. This response has been shown to activate a variety of immune effector cell responses, including an increase in macrophage and killer T-cell activity. Since these heteropolysaccharides are considered to be among the most important of the active compounds in medicinal mushrooms, it is useful to look at them in closer detail for a moment.

In fungi, polysaccharides are often molecularly bound to various proteins. Proteins are molecules that closely represent the unique identity of organisms, and thus often activate the immune system as they enter the body. They can sometimes initiate an immune response which does not act as a beneficial stimulant or tonic but can induce a powerful immune overreaction-leading to an allergic response, for instance as in casein from milk products or gluten from wheat or grass pollens. This response can even be life-threatening, such as in a bee or wasp sting. I know of no reported cases of people having such extreme immunological responses to proteins in the medicinal mushrooms covered in this book; however, some people are known to have idiosyncratic (highly individualized) reactions to such usually safe mushrooms as Boletus edulis. It is unknown what the allergenic compound(s) are. On the flip side, a number of mushrooms are said to increase the beneficial immune-activating response of the body.

There are several questions that come up when one considers exactly what role the polysaccharides or protein-bound polysaccharides play in the overall benefits ascribed to the herbs and mushrooms that contain them.

Many existing scientific studies on medicinal mushrooms and their active components are performed with test animals such as rats and mice, where extracts of various kinds are injected, rather than given orally. It is pertinent to ask how this applies to humans using fungi for food and medicine. Do the polysaccharides, which are large molecular weight molecules, make it past the highly acidic environment of the stomach and the alkaline environment of the duodenum? Do the polysaccharides work when taken orally, or do they have to be injected? Also, when a tincture is made from the mushrooms (extracted with alcohol and water), how does the alcohol affect the polysaccharides or proteins? Are they destroyed by the alcohol, or partially broken down so that their activity is reduced? What aspects of the immune system do they activate (T-cell function and growth, macrophage activity, etc.), and how long does the activity last? While we do not know all the answers to these questions, there is some evidence to support the positive activity of polysaccharides orally, and a low (below 25%) percentage of alcohol does not seem to destroy all their beneficial effects. For instance, the world’s oldest echinacea product that is still manufactured today is made from the freshly-pressed juice of Echinacea purpurea (L.) Moench and then stabilized with about 24% ethanol. Because no other active compounds have been demonstrated (such as alkylamides), the manufacturer points to the polysaccharides as the immune-activating principle. Other studies have shown that while very large molecular-weight polysaccharides (about 800,000) activate a wide variety of immune functions, after reducing the size of the molecules by heating, the range and strength of the activity is proportionately reduced (Adachi, 1990). Small compounds with a molecular weight of about 6400 show only the ability to activate glucose consumption (possibly lowering blood glucose) and synthesis of lysosomal enzyme (an anti-bacterial protective function).

Various polysaccharides and protein-bound polysaccharides (i.e. they occur naturally bound to protein molecules) have shown strong antitumor and immune-enhancing effects.

I have summarized a number of representative studies about active polysaccharide-containing fractions from medicinal mushrooms in Table 4. More detailed information can be found in the individual monographs.

Table 4
SHIITAKE, Lentinula edodes
Polysaccharide/ Protein Activity Subjects Ref.
lentinan (a polysaccharide containing no protein; must be administered by injection) accelerates dengeneration of tumor cells animals & humans Kosaka,1986
increases T-lymphocytes; improves health of chronic hepatitis patients animals Liu,1987
inhibits HIV virus; benefits AIDS patients humans Lin,1987;
Iizuka,1988,
1990a,b
LEM (a protein-bound polysaccharide) benefits chronic hepatitis sufferers humans Izuki,1986;
liver protectant, anti-viral, and immune stimulating animals Mizoguchi,1987b;
Lin,1987
hiv inhibitor animals Aoki,1984a
TURKEY TAIL, Trametes versicolor
Polysaccharide/ Protein Activity Subjects Ref.
psk/krestin (a water-soluble, protein-bound polysaccharide) inhibits binding of HIV with lymphocytes in vitro Tochikura, 1987a
immunopromoter antioxidant activity animal Zhu, 1987
antioxidant activity animal Nakamura, 1986
interferon and antitumor activity animal Ebina, 1987a
many chronic ailments improved with administration orally and by injection human see monograph p. 161
cancer patients show increased life span human see monograph
OYSTER MUSHROOM, Pleurotus ostreatus, (Jacq:Fr.) Quél
Polysaccharide/ Protein Activity Subjects Ref.
acidic polysaccharide fraction 95% tumor inhibition rate against sarcoma-180 from doses of 5 mg/kg animal Yoshioka, 1972
polysaccharide 4% addition to a normal diet was found to lower serum and liver levels of cholesterol after 2 months’ feeding animal Bobek, 1991b
HEN OF THE WOODS, Grifola frondosa
Polysaccharide/ Protein Activity Subjects Ref.
fraction-D etc. from Grifola tumor growth inhibition, orally animal Nanba, 1993s

Of course polysaccharides are not the only active constituents found in fungi, nor do they show only antitumor activity. Smaller compounds, such as terpenes and steroids, have also been found, and some of these have shown antitumor activity. And a great number of polysaccharides and protein-bound polysaccharides have been shown to have antibiotic and antiviral properties, as well as the ability to lower blood pressure and reduce blood levels of lipids (that is, fatty acids) and sugar (Lindequist, 1990). These active compounds make many fungi useful for treating infections, flu, diabetes, heart conditions, and perhaps even AIDS.

Following is a summary of research on the three fungi discussed above in the section on Chinese medicine. These fungi are by no means the only ones studied, but two of them, ling zhi or reishi (Ganoderma lucidum) and shiitake (Lentinula edodes), are perhaps the best-known and most extensively studied mushrooms in the world. For more complete information on their chemistry and pharmacology, as well as literature references to document all of the uses, please refer to the monographs in the second half of this book.

REISHI – LING ZHI

In numerous clinical trials conducted on humans over the last 20 years, Ganoderma lucidum has been used to treat a wide variety of disorders, including:

neurasthenia, dizziness, insomnia, rhinitis, and duodenal ulcers
retinal pigmentary degeneration, leukopenia, progressive muscular dystrophy, and osteogenic hyperplasia
mental disease caused by environmental stress, Alzheimer’s disease, hyper-lipidemia, and diabetes
hepatitis and symptoms associated with anorexia
high-altitude sickness (by oxygenating the blood)

Of special note are reishi’s action on the heart and lungs. In patients with coronary heart disease and hyperlipidemia, reishi has been studied for its ability to alleviate symptoms such as palpitations, dyspnea (sudden difficulty in breathing), precordial pain, and edema, and it seems to lower blood cholesterol and blood pressure. G. lucidum has also been used to treat heart arrhythmias. As for reishi’s effect on the lungs, in one study of over 2,000 patients with chronic bronchitis, reishi brought about marked improvement in 60-90% of the patients. The older patients, especially, seemed to benefit the most (Chang & But, 1986). Bronchial asthma has also been reported to respond well to treatment with G. lucidum, as do several other allergic diseases. Although the antiallergic compounds in G. lucidum are not yet clearly understood, scientists have shown that G. lucidum inhibits the release of histamine, a compound that causes blood vessels to dilate and is responsible for swelling, inflammation, and other allergic reactions.

CORDYCEPS

DONG CHONG XlA CAO

In the clinic, C. sinensis has been studied for the treatment of chronic obstructive liver disorders, high cholesterol, and other aging disorders, including loss of sexual drive, and has shown positive effects. C. sinensis has also been reported to be effective in the treatment of heart arrhythmias, lung carcinoma, and chronic nephritis and kidney failure.

SHIITAKE

Note: “The shiitake mushroom is now Lentinula edodes; this separates it from a number of other Lentinula spp. that are not closely related. DNA studies support this separation. Many other Lentinula species are more closely related to the genus Polyporus (Arora, 1994).”

Two types of shiitake preparations have been studied extensively: lentinan, an active polysaccharide extracted from the fungus, and an extract preparation of the mycelium of Lentinula edodes called LEM (an acronym for “Lentinula edodes mycelia”). In animal studies, lentinan and/or LEM have shown antitumor and antiviral activity, and a distinct stimulation of killer T-cells, which are involved in the immune response. They have also stimulated the production and function of white blood cells, as well as the production of both antibodies and interferon (an antiviral protein), while they have inhibited the synthesis of prostaglandins, which are locally-acting hormones that regulate blood vessel size, mediate inflammation (a protective immune response) and smooth muscle reactivity. Another active constituent of shiitake, eritadenine, may lower levels of cholesterol in the blood (Yamamura and Cochran, 1974a). Table 5 summarizes the important potential uses of shiitake based on studies conducted on both animals and humans.

Table 5:
Summary of Research on Shitake
ACTION TYPE OF
TEST EXTRACT OR FORM DOSE (AMOUNT, ORAL OF IV) REFERENCE
Antitumor in vivo— Mice Lentinan 10 doses of 1 mg/kg body weight (i.p.) Chihara et al. 1970 b
Antiviral in vitro Mice LEM Cultured Mycelia 10 mg/ml Sormiachi et al. 1990 Fujii et al. 1978
Immune enhancement in vivo— Mice Culture cells i.p. Zheng et al. 1985
Lowers blood pressure & cholesterol in vivo— human Shiitake powder Oral Kabir et al, 1987
Protects liver from immunological damage in vitro LEM Animals Mizoguchi et al 1987
Helps produce antibodies to hepatitis B and improves liver function in vivo— Mice LEM —— Harada, 1987
Protects physically active people from overwork and exhaustion; builds vitality in the elderly in vivo— Human Lentinan —— Aoki, 1984b
Inhibits growth of HIV in vitro LEM 0.4mg/ml Tochikura et al., 1987 b
Redues bronchial inflammation in vivo— Human Fruiting body 6-16 g, dry Liu and Bau, 1980
Regulates urinary Incontinence in vivo— Human Fruiting body 6-16 g, dry Liu and Bau, 1980
Anti-cholesteremic in vivo— Human Fresh dried 90g/day
9g/day Suzuki & Oshima, 1974

In human clinical trials, lentinan has shown antitumor activity and has been reported to increase the survival rate and length of life of women with various cancers in hundreds of patients (Aoki, 1984). Today it is commonly used for treating cancer, often in conjunction with chemotherapy. It has also been reported to be useful in treating chronic hepatitis and pulmonary tuberculosis, as well as gastric cancer, pancreatic cancer, leukemia, lymphosarcoma, and Hodgkin’s disease

LEM has inhibited HIV infection of cultured human T-cells in vitro and in clinical trials (Iizuka, 1988, 1990a,b). A symptomatic patient with antibodies to the AIDS virus and a T4 cell count of 1,250/mm3 was given a freeze-dried tea of shiitake mycelium orally at 6 g/day. The T4 cell count improved to 2,045 after 30 days and 2,542/mm3, and the symptoms were much improved after 60 days. The extract also inhibited the production of AIDS virus particles by infected T4 lymphocytes in vitro and increased the production of interleukm 1 by peritoneal macrophages.

LEM may also be beneficial for non-insulin-dependent diabetics because of its reported ability to lower blood sugar levels. In Japan, lentinan is currently classified as a drug, while LEM is considered a food supplement. Note that LEM or other concentrated extracts are probably preferable to raw shiitake for medicinal purposes because they are more concentrated and are easily absorbed in the digestive tract, but using the mushrooms in cooking and in teas may also be effective. It is known that large overdoses of 10 to 50 times the normal clinical dose can lead to immune suppression, or it simply will not have any immunopotentiating effect. Otherwise, side effects are few, except for skin rashes that clear up shortly after discontinuing the extract.

Excerpt from Medicinal Mushrooms