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Agaricus Max
Article 1

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Agaricus Blazei Murrill (Hime-matsutake) is a newly discovered species of mushroom that is attracting the attention of many scientists in the world now. Artificial cultivation of this Brazilian mushroom was achieved for the first time in the world by Iwaide Fungology Institute (founder: Dr. Inosuke Iwaide, a professor at Tokyo University and Mie University) after many trials and errors. This mushroom was presented by professors Hitoshi Ito, Keishiro Shimura and Sensuke Naruse of mushroom research group at Mie University medical school as a highlight at the "the 39th General Meeting of Japanese Cancer Academy" in 1980.

  • Agaricus Blazei Murrill is a carcinostatic food that improves the immunity function of human body

Through the joint research by Mie University medical school, Kobe University faculty of agriculture and Iwade Fungology Institute, it was announced at various academic meeting that Agaricus Blazei Murrill (Iwaide's 101 strains) has anticancer effect against implanted solid cancer, ascites cancer and cancer induced by carcinogenic chemicals on test animals and various other medical effects including inhibition of hepatopathy induced by carbon quadrichloride, decholesterolization, reduction of serum lipid, activation of the third component in complement system and interferon induction. It was also found out through recent study that it activates helper-T lymphocyte, controls immunity system, activates macrophage, activates the function of cell membrane skin system and accelerates enterokinesia against gallbladder cancer. Furthermore, it has been proven that it has antiallergy effect and accelerates cardiac movement.

1. The surprising anticancer effect of Agaricus Blazei Murrill

When carcinoma cells called "Sarcoma 180" is transplanted to subcutis of 5 - 6 week old mice, the carcinoma cells proliferate into a big tumor (cancer) and most of such mice will die within 4-5 weeks.

After transplanting carcinoma cells and making sure that they are settled, certain solutions containing physiological saline and polysaccharides of various fungi including Agaricus Blazei Murrill were administered to the mice daily for 10 days, starting from 24 hours after transplanting. The size of cancer and proliferation impediment rate was periodically monitored and compared to control group of mice, to which only physiological saline was administered. Observation was continued for 60 days with different fungus used for the solution, and anticancer effect of each mushroom was determined by comparing the number of mice from which the cancer completely disappeared. From the result shown in "Table 1: Complete Disappearance of Cancer", Agaricus Blazei Murrill has demonstrated eminent anticancer activity with its complete disappearance rate of 87.5% and cancer impediment rate of 93.6% through administration of 10mg of polysaccharide per 1kg of mouse body weight.

2. Discovery of anticancer active components of Agaricus Blazei Murrill

Six kinds of high polymer polysaccharides have been found as carcinostatic active components of Agaricus Blazei Murrill (see Table 2). FIII-2-b (complex of b-(1-6)àD-glycan and protein) and RNA (nucleic acid) complex showed a remarkable anticancer activity. These substances were confirmed as anticancer active components obtained from the mushroom.

3. Carcinostatic polysaccharides obtained from cultured mycelium and filtrate of Agaricus Blazei Murrill

Many kinds of carcinostatic polysaccharides (Polysaccharides are also referred to as glycans. A glycan is a high polymer sugar containing many interconnected simple sugars such as glucose or xylose.) are contained in the fruit body (mushroom body) of Agaricus Blazei Murrill.

On the other hand, carcinostatic polysaccharides can also be obtained from the mycelium of Agaricus Blazei Murrill. Fungal seeds of Agaricus Blazei Murrill will be cultivated in a liquid culture media containing glucose, yeast extract, small amount of mineral salts and water for a long time under a fixed temperature. Then the mycelium gets centrifuged and goes through thermal extraction. Ethyl alcohol will be added to its culture filtrate in order to obtain precipitation of polysaccharides. Carcinostatic polysaccharides can also be extracted from the filtrate section obtained through cultivation of the mycelium.

Polysaccharide AB-P is obtained from the fruit body, ATOM from the culture mycelium and AB-FP from the filtrate of Agaricus Blazei Murrill. In the comparison experiment of mice carrying "Sarcoma 180" cancer, 10mg of AB-FP per 1kg of mice weight was administered for 10 days. Four weeks later, the tumor inhibition rate was found to be 100%. 20mg of ATOM and AB-FP also showed the tumor inhibition rate as high as 99%. Complete disappearance rate at five weeks was also close to 100%. From these results, it is confirmed that these polysaccharides have extremely high anticancer effect.

AB-P Agaricus Blazei polysaccharide
ATOM Antitumor Organic Substance Mie
AB-FP Agaricus Blazei culture filtrate polysaccharide

4.Cancer prevention effects observed through animal experiments

Cancer proliferation inhibition effect of Agaricus Blazei Murrill is confirmed through experiments with mice. Administration of antioncogenous polysaccharide originated from Agaricus Blazei Murrill to the subject mice was started from 10 days before cancer transplanting. Then "Sarcoma 180" solid cancer was transplanted to subcutis of the mice 24 hours after the final administration. After the transplantation, polysaccharide was not administered to the mice. Physiological salt solution was administered and the same cancer was transplanted to another group of mice for comparison. Anticancer effect was judged by comparison of tumor inhibition, complete disappearance and survival rates. From the result shown in Table 3, complete disappearance was observed in 5 cases out of 10 for the group of mice that received 10mg/kg and in 7 cases out of 10 for the group which received 20mg/kg. Tumor impediment rate was 64.1%, 79.6% and 94.2% for the group that received 5mg/kg, 10mg/kg and 20mg/kg respectively. Thus, anticancer effect was confirmed and it is dependent on the amount of polysaccharide.

5. Agaricus Blazei Murrill is also effective against cancer induced by chemical carcinogen

It is said that more than 80% of human cancer is caused by chemical substances in the environment. Neutral polysaccharides (b-D-glycan, xyloglycan), acid hetero-polysaccharide (uronyde, a kind of galactoglycan), proteinic polysaccharide (peptide glycan) and nucleic acid elements (ribonucleotide protein) are the components of Agaricus Blazei Murrill enabling anticancer activity.

Fibroblastemic sarcoma (cancer) induced by chemical carcinogen called methylcholanthrene was transplanted to subcutis of mice. FIII-2-b originated from Agaricus Blazei Murrill (complex of b-D-glycan and protein), 5-FU (fluorouracil) and ATOM (mycelium polysaccharide obtained from Agaricus Blazei Murrill) were administered to the mice from 24 hours after the transplantation in order to examine the anticancer effect.

From the result shown in Figure 2, it is observed that FIII-2-b and 5-FU inhibits the proliferation of cancer independently. It is also confirmed that 5-FU, when administered together, remarkably increased the anticancer effect of polysaccharide extracted from Agaricus Blazei Murrill. Cell-destroying anticancer medicine also affects normal cells. Strong side effects are expected especially in hematopoietic, bone marrow and digestive systems. However, it is possible to reduce the dosage and side effects by using Agaricus Blazei Murrill concomitantly. It also enables long term administration of anticancer medicine to increase the effect of treatment.

It was confirmed from the result of Table 4 that a mycelium polysaccharide of Agaricus Blazei Murrill also shows anticancer activity against fibroblastemic sarcoma.

6. Agaricus Blazei Murrill is effective against naturally generated adenocarcinoma of mammary gland of mice

The tumor called "Shionogi 42" is the adenocarcinoma that naturally generated in the mammary gland at the left groin of female mice of "dds (DS) family" that were raised in Aburabi Farm at Shionogi Co., Ltd. Research Center in 1959. This cancer is transplantable to DS mice of family only and as shown in Table 6, it is difficult to cure this cancer with conventional anticancer medicine.

The tumor inhibition rate 25.1% as the result of ATOM administration at 100mg/kg dosage is not so convincing, but at 300mg/kg dosage, the inhibition rate rose to 48.5%. It was also observed that polysaccharide originated from Agaricus Blazei Murrill shows stronger cancer inhibition activity than anticancer medicines such as mitomycin C (antioncogenous antibiotic) or fluorouracil (pyrimidine metabolism antagonizing antitumor medicine).

7. Steroid content of Agaricus Blazei Murrill inhibits proliferation of uterocervical cancer cell that originated in human body

Agaricus Blazei Murrill's inhibition system inhibits, destroys and stops proliferation or metastasis of carcinoma cell by activating and reinforcing the self-defense system naturally endowed to the host, i.e. immunity function. This function can be divided into specific and non-specific immunity. Typically, immunity function is exercised by lymphocyte (T- and B-lymphocyte) that exists in the blood, antibody (globulin), complement, macrophage (a serum protein enzyme that plays an important role in bacteriolysis, phagocytosis and immune cytolysis, activated by various antigen-antibody reaction), leukocyte, etc. In addition to various polysaccharides which shows anticancer activity by strengthening the immunity function, Agaricus Blazei Murrill contains steroids that directly affect carcinoma cells and inhibit cancer proliferation in the manner similar to that of typical chemotherapeutic medicines. Three out of six kinds of steroids dissociated from the acetone extract of Agaricus Blazei Murrill were found to have inhibition effect against the proliferation of carcinoma cell in a test tube.

It is reported that the steroids with structures shown as formula 1,2 and 4 of Figure 3 inhibited the proliferation of carcinoma cells at such low density as 8ppm, 16ppm and 64ppm respectively, in an experiment using HeLa cells (uterocervical cancer cell that originated in human body).

Ergosterol, a precursor of vitamin D, does not show an anticancer action by itself. However, it has been made clear that the new synthetic steroid biosynthesized from ergosterol (structural formula 3 of in Figure 3) also works as an inhibitor against proliferation of carcinoma cells. Even if carcinoma cells are generated in the body, it does not immediately start carcinogenesis. Considering the fact that it takes years for carcinoma cells to proliferate and undermine the body and finally cause carcinogenesis, it can be said that Agaricus Blazei Murrill is a mushroom of wonder that prevents every disease with its steroids content, directly inhibiting the proliferation of carcinoma cells.

8. Concomitant use of Agaricus Blazei Murrill and anticancer medicine results in synergistic effect

Krestin (PS-K) extracted from trametes versicolor, a mushroom of polyporaceae family and letinan made of polysaccharide extracted from lentinula edodes are clinically used as medicines for immunotherapy. These medicines are said to be more effective when used with other anticancer (chemotherapeutic) medicines. Concomitant use of polysaccharide extracted from the mycelium of Agaricus Blazei Murrill (ATOM) and other anticancer medicines was examined using Sarcoma 180 solid cancer. Starting from 24 hours after transplantation of the cancer, ATOM was administered to the mice in the abdomen for 10 consecutive days and other anticancer medicines were administered by injection 3 times a week, for 2 weeks. As shown in Table 5, through concomitant use with ATOM, it resulted in 4.8 times for mitomycin, 6.8 times for endoxan, 2.1 times for cytosine arabinosid and 6.3 times for fluorouracil synergistic effect compared to single use of respective anticancer medicine. The data suggests that the immunity activation effect of polysaccharide from Agaricus Blazei Murrill increases the anticancer activity of other medicines and more effective extermination of cancer can be expected by impeding the proliferation of carcinoma cell through concomitant use.

9. Agaricus Blazei Murrill enhances the cancer treatment effect of radiotherapy

Radiotherapy is a popular cancer treatment method, but it also has a disadvantage of attacking normal cells as well as carcinoma cells. NFT (Nakahara-Fukuoka Tumor) is a fiber sarcoma that naturally generated in the subcutis of mice. This sarcoma was named after the doctors Kazuro Nakahara and Fumiko Fukuoka at National Cancer Center of Japan who discovered it in 1949.

Administration of ATOM does not produce anticancer effect against this tumor. When it is administered twice with a week's interval to NFT cells that received X-ray irradiation of 1500R, the mortality of mice drops, but the tumor does not disappear completely. However, it was confirmed that through concomitant use of Agaricus Blazei Murrill polysaccharide (ATOM) and radiotherapy, the tumor in 40 - 50% of the mouse disappears completely. As to Shionogi 42 cancer, when AST cells were administered of ATOM twice with a week's interval after receiving X-ray irradiation of 1500R (this amount was found to be appropriate through preliminary experiments), complete disappearance rate increased and mortality remarkably dropped. Thus, synergistic anticancer effect through concomitant use of Agaricus Blazei Murrill and radiotherapy was confirmed in animal experiments. This mushroom plays an important clinical role when used with radiotherapy as well as anticancer medicines. Furthermore, the synergistic effect of ATOM and radiotherapy was found to be more effective to female mice than male mice, as shown in Table 6. Considering the similarity between mice and human being in the aspects of life span difference between men and women, the data is very interesting because it may be suggested that the same is true for human being.

10. The first step of treatment by anticancer medicine is to understand its side effect.

Curing cancer is an earnest wish of mankind. Unlike foreign microorganism, carcinoma cells are part of human body system and have few differences from normal cells. This is the reason why anticancer medicine cannot fully control the disease. In other words, there is yet no anticancer medicine effective specifically against carcinoma cells. In some cases, unfortunately, patients die sooner from lethal complication caused by the side effect, even though the number of carcinoma cells may be reduced by the treatment using anticancer medicine. Side effect is a big obstacle in the use of anticancer medicines. There is no medicine without side effect and medicines with fewer side effects are less effective against cancer. So, it is important to understand the side effect as the first step of treatment by anticancer medicines.

Many anticancer medicines clinically used today make a covalent or non-covalent bond with DNA and affect the replication, transcription and translation of DNA. Ironically enough, such medicine itself is sometimes carcinogenic. It is commonly known that many of nitrogen mustard derivatives used as alkylating medicines increase pulmonary and thymus tumor of mice. It is also known that cyclophosphamide and endoxan increase mammary gland tumor and mitomycin C used as antitumor antibiotic increases subcutaneous sarcoma of mice. As such, an anticancer medicine ultimately has a possibility to affect human body as a carcinogenic agent. Patients should be aware that it is possible that an anticancer medicine used to cure the primary cancer may cause the secondary cancer.

11. Agaricus Blazei Murrill helps recovery from the inhibition of reticuloendothelial system function caused by anticancer medicines

Popular clinical anticancer medicines such as mitomycin C (MMC), fluorouracil (5-FU) and cyclophosphamide (CY) are known to more or less inhibit the reticuloendothelial system function. In a study made under the condition of Ehrlich ascites and gallbladder cancer, whereas K-value of the subject group is 100, the K-value was significantly inhibited to 57% for group administered with 1mg/kg of MMC, 60% for 20mg/kg of CY and 72% for 30mg/kg of 5-FU (see Figure 4).

At the same time, ATOM was found to prevent the said inhibition of the reticuloendothelial system function caused by anticancer medicine administration. Thus, the concomitant use of ATOM and anticancer medicine reduces the side effect caused by the anticancer medicine and improves the treatment effect.

12. Agaricus Blazei Murrill stimulates the immunocompetent cells, improves the immunity function and stops the activity of cancer

Figure 5 is the result of study made under gallbladder cancer condition with weak immunity function to see whether Agaricus Blazei Murrill shows an action to help the recovery of the immunity function. When the polysaccharide extracted from Agaricus Blazei Murrill was administered, the level of Thy1 and 2 positive cells (marker of all T-cells), L3T4 positive cells (marker of helper/inducer T-cells) and Asisalo GM1 positive cells (marker for natural killer cells and activated macrophage) significantly increased. From this result, it can be observed that Agaricus Blazei Murrill prevents carcinoma cell activities by strengthening the helper T-cells (commanders of immunity system) and cooperating with macrophage and natural killer cells (guards and soldiers).

13. Agaricus Blazei Murrill is also effective against ascites cancer

Polysaccharides extracted from mushrooms of polyporaceae family are generally effective against sarcoma 180 solid cancer. But it is said that this effect cannot be expected against ascites cancer where the growth of cancer is slow (they are scattered and floating under the peritoneum) such as Ehrlich ascites cancer.

When ascites cancer is transplanted, all subjects die from it within 2 weeks. Animals are considered to die from fast growth of ascites cancer cells while the polysaccharides cannot improve the cancer inhibition function of immune system in time. However, there are data (Table 7) to show the effectiveness of Agaricus Blazei Murrill in animal experiments with ascites cancer, for which the same effect could not be expected by using traditional immunoactivating medicines.

14. Agaricus Blazei Murrill's lipid section is also anticancer active

In addition to Agaricus Blazei Murrill's various polysaccharide section, its lipid section was also found to have anticancer effect. As shown in Figure 6, a group of mice (10 subjects) transplanted of ascites cancer survived only 15.0 days as an average. But another group administered with 150mg/kg of lipid section of Agaricus Blazei Murrill survived 19.7 days and with 300mg/kg survived 30.6 days as an average. The cancer on 2 subjects out of 10 had completely disappeared. Thus, the lipid section was confirmed to be anticancer active against Ehrlich ascites cancer.

15. Agaricus Blazei Murrill activates macrophage

Agaricus Blazei Murrill contains 3.6 % of lipid, of which 26.8% is neutral lipid and 73.2% is phospholipid. So phospholipid is the primary part of the mushroom's lipid. The lipid can be decomposed into linolic, palmitic, oleic and palmitoleic acids, each of which is observed to be anticancer active against ascites cancer. Macrophage was also found activated in the group of mice administered with the lipid section of Agaricus Blazei Murrill. It is known that such activated macrophage plays an important role in biophylaxis in addition to anticancer activity.

16. Agaricus Blazei Murrill proved to be more effective against ascites cancer than other anticancer medicines

Antioncogenous polysaccharides obtained from other mushrooms are generally considered to be effective only against solid cancer. However, as already explained, polysaccharides obtained from Agaricus Blazei Murrill is effective against ascites cancer as well as solid cancer. Table 8 is the result of comparison between the anticancer effects of Agaricus Blazei Murrill polysaccharide (ATOM) and other anticancer medicines against Ehrlich ascites cancer transplanted to mice. ATOM and other anticancer medicines were administered in the amount shown in Table 8 for 10 consecutive days, starting from 24 hours after the transplantation. Comparing the number of survival days of each group of mice, the group administered with 100mg/kg of ATOM survived 168.5% longer than the control group. Furthermore, the longevity rate remarkably increased to 237% by concomitantly using MFC (administration of 1/3 of appropriate dosage of mitomycin C, fluorouracil and cytosine arabinosid). It was also confirmed that ATOM by itself at 50mg/kg and 100mg/kg dosages was more effective in anticancer activity than fluorouracil or cytosine arabinosid. Thus, ATOM extracted from Agaricus Blazei Murrill is more effective against ascites cancer than other anticancer medicines for clinical use.

17. Agaricus Blazei Murrill activates reticuloendothelial system function

Reticular cells in liver, spleen, lymphoid tissues and bone marrow and macrophage neutrophils in lungs and under peritoneum are typically involved in reticuloendothelial system activity. In the experiment of administering 150mg/kg and 300mg/kg of Agaricus Blazei Murrill polysaccharide (ATOM) for 10 consecutive days from 24 hours after transplantation of Ehrlich ascites cancer, the phagocytosis index K (the unit of reticuloendothelial system activity indicating its capacity to catch and eat large particles such as bacterium, protozoa, perished tissue cell and colloid particle. Carbon clearance values were examined as its guideline in this experiment) rose significantly in comparison with the control group (see Figure 7).

This result is at the same level as the one obtained by administration of 10KE/kg of picibanil (an immunopotentiative anticancer medicine obtained from streptobacteria of group A, type 3) or 100mg/kg of PSK (an immunopotentiative anticancer medicine obtained from mycelium of trametes versicolor).

The organ weight of liver, spleen and thymus increased significantly in comparison with the control group, by orally administering ATOM under Ehrlich ascites cancer as shown in Figure 8. Since liver and spleen create single-nucleus cells including macrophage and thymus involved in the immunity activity, such increase in their weight it suggests that concomitant use of ATOM with anticancer medicines is effective from the aspect of side effect reduction in cancer treatment.

18. Agaricus Blazei Murrill can be a solution to allergic diseases without fear of side effects

When foreign substance (antigen) such as virus, drug, pollen or indoor dust enters human body, the human body distinguishes the substance and makes a weapon (antibody) to attack and expel such substance. This is called immunoreaction. Symptom of allergy such as asthma and atopy breaks out in the same manner as immunoreaction. Normally, immunoreaction occurs in order to protect the body from germs. However, in the case of a person with allergy, the reaction lacks normal control and it does harm to the body. The cause of allergy is an antibody called IgE (immunoglobulin E) created by B-cells which are involved in immunity system. Substance which triggers allergic reactions such as cedar pollen or mite are called allergen. When the body is repeatedly exposed to allergen, the antibody IgE will be created. And the antibody IgE attached to mast cells discharges substances including histamine, causing organic reactions including an itchy feeling. Symptoms such as atopic dermatitis, allergic rhinitis and bronchial asthma are caused by histamine.

Therefore, antihistaminic that controls the isolation of histamine from mast cells is used for treatment of allergy as well as steroid. But traditional antihistaminic very frequently causes sleepiness as a side effect. We have so far learned that Agaricus Blazei Murrill, as its anticancer action, is closely involved in the functions of macrophage and complement supporting the immunity system, activation of reticuloendothelial system and T-lymphocyte functions. So we examined the antiallergy effect of ABWE (hot water extract of Agaricus Blazei Murrill). The experiment result is shown in Tables 9 and 10, and in Figure 9. See Table 9 first. This is the result of inhibition of histamine isolation from peritoneal mast cells of unsensitized rats that was induced by compound 48/80 (histamine isolator). Administration of 200mg/ml, 500mg/ml and 1000mg/ml of ABWE resulted in isolation rate of 77.2±5.7%, 67.4±5.7% and 49.1±5.0% and inhibition rate of 11.9%, 23.1% and 44.0% respectively.

Table 10 shows the isolation of histamine from cells sensitized by antiserum involving antibody IgE. The isolation rate after administration of 200mg/ml, 500mg/ml and 1000mg/ml of ABWE was 28.9±3.0%, 24.6±2.1% and 20.1±2.3% and inhibition rate was 3.9%, 19.1% and 33.9% respectively. The inhibition rates with 500mg/ml and 1000mg/ml are significant. Figure 9 shows the inhibition of histamine contraction of a guinea pig intestine piece. Immediately after 1ml of 120,000x histamine solution was infused, a strong intestinal contraction started as shown in the figure. While the contraction continued, 1ml of 1,200,000x solution of diphenhydramin was infused. Then a strong inhibition action was immediately observed. A similar experiment was made with 1ml of 10x ABWE solution using another piece of intestine. The inhibition action was observed after a latent period of about 2 minutes (see the middle line of the figure). This inhibition action was also observed with 1ml of 50x ABWE solution (see the bottom line of the figure).

Unlike other medicines, an edible mushroom Agaricus Blazei Murrill will not cause any side effect.

19. Clinical data confirms that Agaricus Blazei Murrill improves hepatic function

From the data obtained through my joint research with Dr. Wang Jun Zhi of Lanzhou Medical Institute of China, daily administration of 20mg of Agaricus Blazei Murrill brought about various effects including hepatic function improvement and negative index of virus activity in chronic hepatitis B patient (see Table 11).

Dr. Wang divided 20 patients into an experimental group and a control group. Each member of the experimental group took Agaricus Blazei Murrill and the control group received ordinary treatment only. The result was compared 3 months later and it was confirmed that the treatment effect on the experimental group was 2 significant, 8 effective and 0 ineffective, while the effect on control group was 1 significant, 6 effective and 3 ineffective. The difference in hepatic function improvement is especially noteworthy. GOT, GPT, connective bile acid, serum iron protein, total bilirubin and prothrombin values of the experimental group also indicated the mushroom's remarkable effectiveness in keeping hepatic function in order. These clinical data proves that Agaricus Blazei Murrill promotes the recovery of the hepatic cell of a chronic hepatitis patient. And the effect will be retained after treatment.

20. Agaricus Blazei Murrill's immunopotentiation effect strongly supports pancreas

Let me explain about Agaricus Blazei Murrill's effect against diabetes, a life custom disease that causes various complications. Diabetes is caused by insufficiency of insulin, a hormone that is secreted from pancreas. Insulin helps human body utilize glucose as a source of energy. When there is an insufficiency of insulin, human body cells cannot absorb the energy and the sugar will be left in the blood. Under this condition, human body becomes easily tired and its resistance against foreign enemy becomes weak. As a result, infectious diseases and various disabilities may be caused. Therefore, in order to control the blood sugar value, medical treatment is very important as well as dietary control and physical exercise. Insulin will be administered for diabetes. However, any effective medicine carries a risk of side effect, depending on the usage. In the case of insulin, it may cause hypoglycemia as a side effect. Considering the possibility of a treatment that is safe and independent on medicines, Agaricus Blazei Murrill would play a really big role with its immunopotentiation effect.

Agaricus Blazei Murrill research group has confirmed the effect in the experiment of mice with diabetes. The disability of the Langerhans' islands of their pancreas caused the diabetes. Agaricus Blazei Murrill successfully activated the immunity system of these mice and inhibited the progress of diabetes (see Chart 1).

21. Agaricus Blazei Murrill contributes to the prevention of diabetes-related complications

It is regrettable that it is still impossible to cure diabetes completely, even with the advanced medicine of today. However, neglecting the disease may lead to various complications and it is sometimes fatal. Therefore, treatment of diabetes is focused on control of blood sugar level and prevention of complications. Vegetable fiber is said to be effective in preventing the increase of blood sugar level. Vegetable fiber means everything that cannot be digested with human digestive enzyme, such as indigestible high polymer polysaccharides, cellulose, pectic substance, chitin and chitosan.

It is important to take vegetable fiber as a treatment of diabetes because (1) vegetable fiber contains low energy, (2) it is not insulin-stimulant and (3) it causes inhibition and delay in absorption of nutrient, so that it slows down the rise of blood sugar level.

Agaricus Blazei Murrill contains abundant vegetable fiber such as b-D-glycan, heteropolysaccharides (pectic substance, hemicellulose) and chitin. In order to avoid complications, it is also important to prevent arteriosclerosis as well as keeping normal blood sugar level. Agaricus Blazei Murrill also contains linolic acid. Linolic acid has a similar function as vegetable fiber to reduce blood cholesterol (see Figure 10).

Agaricus Blazei Murrill is also a food of high nutritive value, since it contains various amino acids, vitamin B and D, magnesium, potassium, etc. Diabetes patients tend to become sensitive about calorie value and take low energy meals with insufficient vitamin and mineral. Agaricus Blazei Murrill contains abundant vitamin and mineral and will provide desirable supplementary nutrition.

Treatment of diabetes takes a long time. Instead of using medicines with a threat of side effects, patients can take Agaricus Blazei Murrill without any fear. This is an important option for diabetes patient.

22. Many effective components included in Agaricus Blazei Murrill repair and maintain homeostasis

Due to the problematic medical practice of "soaking" patients with medicine and patients' anxiety related to it are urging patients to look at oriental medicine. Anyway, what do we expect from oriental medicine? One of the things we expect must be its attitude towards diseases. In oriental medicine, every disease is caused by the disorder of homeostasis of body. A disease is a local result from loss of balances between false/true, cold/hot, positive/negative and spirit/blood. Therefore, oriental medicine focuses on repairing homeostasis and increasing immunity. With such a philosophy, oriental medicine is useful in treating physical weakness during the recovery period from a disease and chronic or ill-defined diseases such as fatigue, cold constitution, lumbago, climacteric disorders and anxiety. While repairing homeostasis, Chinese herbs are also considered to be effective against chronic hepatitis, chronic rheumarthritis and bronchial asthma, which cannot be cured by western medicine. Numerous well-balanced components of Agaricus Blazei Murrill will correct the lost balances, ease various strains and maintain homeostasis. The b-D-glycan is also contained in the mushroom for improvement of immunity function. The edible mushroom Agaricus Blazei Murrill's effect in improving both homeostasis and immunity will also be well supported from the viewpoint of oriental medicine.

Table 1

The effect of polysaccharides extracted from basidiomycetes and bacteria against "Sarcoma 180" solid cancer

Name Dosage (mg/kg x days) Complete disappearance rate Tumor impediment rate
Agaricus Blazei Murrill (Iwaide's 101 strains) 1x10 10/16 80.7
  10x10 28/32 93.6
Fomitopsis pinicola(cultivated) 10x10 5/10 73.4
Tremella fuciformis 10x20 4/8 75.2
  50x16 0/8 66.7
Fomitopsis castanea 10x10 0/9 64.8
Inonotus flavidas 10x10 3/10 76.9
Trametes versicolor (cultivated) 10x10 6/8 88.7
  50x10 8/8 92.9
Polyporus umbellatus 0.5x10 25/30 83.3
  1x10 26/30 86.7
Ganoderma lucidum 20x10 5/10 83.9
  100x10 4/10 68.2
Trametes orientalis 10x11 0/8 60.4
Penicillium (cultivated) 10x11 0/8 33.3
Plant damping-off germ (cultivated) 10x11 3/8 79.6
Bjerkandera dichrous 10x11 1/8 75.2
Morchella esculenta 10x11 1/8 77.1
Control Group (Physiological saline 0.25ml) x10 0/68 -

Tumor impediment rate was judged at week 4.

Table 2

Polysaccharide contents of Agaricus Blazei Murrill which showed significant anticancer effect against "Sarcoma 180" solid cancer

Polysaccharides extracted from fruit body Average number of molecules (in 10,000's) Tumor inhibition rate (%) Complete disappearance rate (dis-appearance/ group size) Mortality (deaths/ group size) Dosage mg/kg/day (injection)
b-glycan F1o-a-b 50 71 1/6 4/6 10x10
a-glycan *1 FA-1-a-a 200 93 4/8 0/8 10x10
b- galactoglycan FA-1-a-b 200 97 5/8 0/8 10x10
Nucleic acid (RNA) *2 FA-2-b-b 1 95 7/8 0/8 10x10
Proteinic glycan FIII-2-b 1 - 5 99 8/10 0/10 10x10
Xyloglycan FIV-2-b 1 - 5 80 4/10 3/10 10x10
Water (control group) - 0 0/6 10/10 10x10

Notes *1 and *2: Even when orally administered (50mg, 150mg/kg/10days), these polysaccharides show high tumor inhibition rates (68% and 74%). This means mice with ascites cancer can still survive.

Table 3

Antitumor effect against "Sarcoma 180" solid cancer after preparatory administration of ATOM (polysaccharide extracted from Agaricus Blazei Murrill)

Treatment No. of days administered Average tumor size (cm3) Tumor inhibition rate (at 4 weeks) Complete disappearance rate (at 5 weeks) Mortality (at 5 weeks)
Control Group (Physiological saline) from day -11 to day -1 32.3 - 0/10 10/10
ATOM (5mg/kg) -11 à -1 11.6 64.1 1/10 4/10
ATOM (10mg/kg) -11 à -1 6.6 79.6 5/10 2/10
ATOM (20mg/kg) -11 à -1 1.9 94.2 7/10 0/10

Each group consisted of 10 mice. ATOM was administered for 10 days and then Sarcoma 180 cancer was transplanted. The day of transplantation is "day 0". ATOM was not administered after the 10-day period.

Table 4

Anticancer effect of ATOM against Meth A fibroblastemic sarcoma

Dosage (mg/kg x days) Administration method Average tumor size (cm3) at 28 days later Tumor inhibition rate (%)
Control group (Physiological saline) Peritoneal 21.23±8.76 -
10x10 Peritoneal 21.01±9.02 1.0
50x10 Peritoneal 9.46±3.65 * 55.4
100x10 Peritoneal 8.32±3.43 * 60.8
Control group (Physiological saline) Oral 23.91±9.98 -
300x10 Oral 14.12±3.01 * 41.0

Meth A fibroblastemic sarcoma was transplanted to female mice of Balb/c family. Starting from 24 hours after transplantation, ATOM was administered by intraperitoneal injection or by mouth. Each control groups consisted of 15 mice and each ATOM experimental group consisted of 10 mice.
* P<0.05, examination of significant difference from control group data

Table 5

Synergistic effect by concomitant use of ATOM and other anticancer medicine against Sarcoma 180 solid cancer

Experimental group (mg/kg x days) Tumor inhibition rate (%) Complete disappearance rate (disappearance/group size)
ATOM (0.5x10) 52.6 0/10
Mitomycin C (0.25x6) 15.8 0/10
ATOM + Mitomycin 76.2 4/10
Endoxan (10x6) 10.4 0/10
ATOM + Endoxan 70.9 4/10
Cytosine arabinosid (10x6) 27.4 0/10
ATOM + cytosine arabinosid 57.2 2/10
Fluorouracil (10x6) 11.5 0/10
ATOM + fluorouracil 72.5 3/10

Sarcoma 180 was transplanted to female Swiss mice (6 weeks old). ATOM was administered once a day for 10 days, and other medicines 3 times a week for 2 weeks by intraperitoneal injection. The result was judged at week 4.
Complete disappearance was confirmed for all members of the group administered with 5mg/kg of ATOM for 10 days.

Table 6

Synergistic anticancer effect of ATOM and radiotherapy

Experimental group Complete disappearance rate (disappearance/group size) Mortality
(deaths/group size)
(mg/kg x days) Male Female Male Female
Control group (NFT) 0/10 0/10 10/10 10/10
ATOM (100x20) 0/10 0/10 8/10 8/10
X-NFTx2 0/10 0/10 8/10 7/10
ATOM + X-NFTx2 4/10 5/10 3/10 2/10
Control group (AST) 0/10 0/10 10/10 8/10
ATOM (100x20) 0/10 0/10 8/10 10/10
X-ASTx1 1/10 2/10 5/10 3/10
X-ASTx2 2/10 4/10 3/10 2/10
ATOM+X-ASTx2 5/10 6/10 1/10 0/10

50mg/kg of ATOM was administered twice a day for 20 consecutive days to applicable groups of mice of DS family (27±4g). Then NFT and AST was transplanted. Radiation of 1500R was given to tumor cells (5 x 106 cells) once or twice at 7-day interval. The complete disappearance rate and mortality was judged at week 5 after tumor transplantation.

  • ATOM: Antitumor Organic Sunbstance Mie
  • NFT: Nakahara-Fukuoka Tumor
  • AST: Aburai Spontaneous Tumor (also called Shionogi 42 cancer)

Table 7

Anticancer effect of ATOM against Ehrlich ascites camcer

Dosage (mg/kg x days) Administration method Average days of survival Longevity rate(%) Complete disappearance rate (disappearance/ group size)
Control group (Physiological saline) Peritoneal 17.81±1.61 - 0/15
10x10 Peritoneal 22.80±2.43 28.0 0/16
50x10 Peritoneal > 47.21±4.30 * 165.1 8/20
100x10 Peritoneal > 49.90±4.71 * 180.2 19/32
Control group (Physiological saline) Oral 18.44±2.23 - 0/20
100x10 Oral > 29.75±3.15 * 61.3 0/10
300x10 Oral > 39.97±3.79 * 116.8 2/10

* P<0.05, examination of significant difference from control group data
Ehrlich ascites cancer was transplanted to male mice of C3H/HeN family. Starting from 24 hours after transplantation, ATOM was administered by intraperitoneal injection or by mouth for 10 consecutive days.

Table 8

Comparison of anticancer effect of ATOM and other anticancer medicines against Ehrlich ascites camcer

Experimental group (mg/kg x days) Group size No. of days survived Complete disappearance rate (disappearance/ group size) Longevity rate (%)
Control group 16 17.8±0.6 0/16 0
ATOM (10x10) 8 22.8±2.4 0/8 28.1
ATOM (50x10) 10 40.2±4.2 4/10 > 125.8
ATOM (100x10) 16 47.8±4.3 12/16 > 168.5
Endoxan (25x10) 10 38.4±7.2 1/10 > 116.7
Daunomycin (1x10) 10 50.3±5.8 3/10 > 182.6
Mitomycin (0.25x10) 10 54.9±6.3 5/10 > 208.4
Cytosine arabinosid (20x10) 10 25.3±1.7 0/10 42.1
5-FU (30x10) 10 31.0±5.2 0/10 74.2
MFC (1/3 each) 10 58.4±4.1 6/10 > 228.1
MFC + ATOM 8 60.0±0 8/8 > 237.0

Ehrlich ascites cancer was transplanted to mice (5 weeks old) of C3H/HeN family. Starting from 24 hours after transplantation, each medicine was administered by intraperitoneal injection for 10 consecutive days and the mice were checked for 60 days.

Table 9

Inhibition of histamine isolation from peritoneal mast cells of unsensitized rats that was induced by compound 48/80 (10mg/ml)

Experimental group Dosage (mg/ml) Histamine isolation rate (%) Inhibition rate (%)
Control group - 87.6±7.0 -
ABWE (Hot water extract of Agaricus Blazei Murrill) 200 77.2±6.7 11.9
  500 67.4±5.7 * 23.1
  1000 49.1±5.0 * 44.0
AH (Antihistaminic) 100 29.2±5.0 * 66.7
  500 10.6±2.1 * 87.9

* P<0.05

Table 10

Inhibition of histamine isolation from peritoneal mast cells of rats sensitized by anti-EWA serum

Experimental group Dosage (mg/ml) Histamine isolation rate (%) Inhibition rate (%)
Control group - 30.4±3.7 -
ABWE (Hot water extract of Agaricus Blazei Murrill) 200 28.9±3.0 3.9
  500 24.6±2.1 * 19.1
  1000 20.1±2.3 * 33.9
AH (Antihistaminic) 100 24.1±1.7 * 20.7
  500 13.8±2.5 * 54.6

* P<0.05, 2mg/ml of EWA (Egg white albumin) was added as an antigen
(source: Ito et al. "Medicine and Biology" July 10, 1995)

Table 11

Clinical research of Agaricus Blazei Murrill's treatment effect to chronic hepatitis B patients
(Data comparison between experimental groups)

Experimental group Group size Sex Average age (youngest - oldest) No. patients diagnosed to have hepatitis B
    Male Female    
Treated with Agaricus Blazei Murril 10 9 1 41 (27-55) 10
Control group 10 8 2 39 (21-57) 10
Treatment method:
  1. Treatment with Agaricus Blazei Murrill: 20g of Agaricus Blazei Murrill and its decoctum were administered by mouth twice a day in addition to general medication (vitamins, ATP, 5-FU, etc.) for 3 months
  2. Control group: General medication (vitamins, ATP, 5-FU, etc.) only

(Changes in hepatic functions due to administration of Agaricus Blazei Murrill)

Experimental group Group size/ Before or after treatment SGPT (U) SGOT (IU/L) Bilirubin(mmol/L)
Treated with Agaricus Blazei Murril 10 Before 83.1±33.2 49.8±18.0 114.1±12.7
    After 24.1±9.0 *¨ 27.3±13.4 *¨ 17.8±4.0 *¨
Control group 10 Before 88.3±35.3 52.6±24.6 103.6±51.0
    After 64.6±28.5 * 40.6±24.9 * 31.4±17.2 *

* P<0.05 Comparison before and after the treatment; ¨ P<0.05 Comparison after the treatment

Changes in hepatic function indices due to administration of Agaricus Blazei Murrill

Experimental group Group size/ Before or after treatment Connective bile acid(µg/dL) Serum iron protein(ng/ml) Prothrombin(S)
Treated with Agaricus Blazei Murril 10 Before 2803±1535 341±137 19.8±3.8
    After 748±951 *¨ 198±111 *¨ 15.0±2.6 *
Control group 10 Before 2803±1189 303±421 19.7±3.1
    After 2456±836 293±29 17.6±2.1 *

* P<0.05 Comparison before and after the treatment;
¨ P<0.05 Comparison after the treatment

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