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Malignant pleural mesothelioma with long-term tumor disappearance of a local relapse after surgery: A case report.

Higashiyama M, Oda K, Okami J, Maeda J, Kodama K, Imamura F.
Journal of Medical Case Reports. 2009;3

Introduction. There have been few reports of spontaneous regression of malignant pleural mesothelioma, but the mechanism for this is unknown. We present a case report on a patient with malignant pleural mesothelioma showing apparent tumor disappearance in a local relapse after surgery. Case presentation. A 73-year-old man presented with malignant pleural mesothelioma in the right thoracic cavity. A pleurectomy was performed, and as expected, the tumor locally relapsed with increasing chest pain. However, the symptoms suddenly improved while the tumor was apparently reduced, and spontaneous tumor regression was initially considered. The patient confessed that he had self-administered a mushroom extract with alternative parasympathetic nerve stimulation therapy thereafter. The complete disappearance of the tumor was clinically achieved during a 29-month follow-up with continuing self-treatment. Conclusion. This is the first report describing a malignant pleural mesothelioma patient in Japan showing long-term complete disappearance of a local relapse after surgery. This event was a tumor regression possibly due to an immunological effect of combined complementary and alternative therapy.

Effect of oral administration of dried royal sun agaricus, agaricus brasiliensis S. Wasser et al. (Agaricomycetideae), fruit bodies on anti-β-glucan antibody titers in humans.

2. Ishibashi KI, Motoi M, Liu Y, Miura NN, Adachi Y, Ohno N.
International Journal of Medicinal Mushrooms 2009;11(2):117-31

Agaricus brasiliensis ( Agaricus blazei Murrill sensu Heinem.) is a health food that has received recent attention. Β-Glucan is one of the major components of A. brasiliensis. We have reported that an anti-Β-glucan antibody was detected in sera from human volunteers. In this study, we examined the reactivity of the anti-BG antibody to A. brasiliensis extracts in human sera and change in the anti-BG antibody titer of healthy volunteers taking A. brasiliensis for 6 months (N 27, average age 43 11, male 13, female 14). Individual differences in the anti-BG antibody titer existed. We evaluated the rate of change in the titer in each individual. The volunteers in the A. brasiliensis group showed an increase in the anti-BG antibody titer as compared with those in the placebo group. Individual differences existed in the rate of the increase. We first demonstrated a clinical effect of the oral administration of A. brasiliensis on the anti-BG antibody titer. The oral administration of A. brasiliensis induced a Β-glucan-specific response and there were individual differences in this response. The resulting anti-BG antibody production could be useful as an index of the immune response to Β-glucan in humans.

Immunomodulating activity of Agaricus brasiliensis KA21 in mice and in human volunteers.

3. Liu Y, Fukuwatari Y, Okumura K, Takeda K, Ishibashi KI, Furukawa M, Ohno N, Mori K, Gao M, Motoi M.
Evidence-based Complementary and Alternative Medicine 2008;5(2):205-19

We performed studies on murine models and human volunteers to examine the immunoenhancing effects of the naturally outdoor-cultivated fruit body of Agaricus brasiliensis KA21 (i.e. Agaricus blazei). Antitumor, leukocyte-enhancing, hepatopathy-alleviating and endotoxin shock-alleviating effects were found in mice. In the human study, percentage body fat, percentage visceral fat, blood cholesterol level and blood glucose level were decreased, and natural killer cell activity was increased. Taken together, the results strongly suggest that the A. brasiliensis fruit body is useful as a health-promoting food.

The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B.

4. Hsu CH, Hwang KC, Chiang YH, Chou P.
Journal of Alternative and Complementary Medicine 2008;14(3):299-301

Background: Hepatitis B is a global health problem. Use of complementary and alternative medicine has been popular among patients with hepatitis B. This 1-year open-label pilot study aims to observe whether Agaricus blazei Murill extract improves liver function in patients with hepatitis B. Methods: This study involved 12 months of clinical observation. Four (4) patients with hepatitis B who met the criteria (1) aged between 20 and 65 years; (2) being Chinese; (3) having been a hepatic B carrier (HBAg(+)) for more than 3 years; (4) alanine aminotransferase > 100 IU/L; and (5) not taking lamivudine, α-interferon, or other drugs for hepatitis participated in the study with informed consent. The enrolled patients were given Agaricus blazei Murill (ABM) extract of 1500 mg daily for 12 months. The level of alanine aminotransferase was taken as the major outcome measurement. Results: At the end of the study, the mean level of aspartate aminotransferase and alanine aminotransferase decreased from 246.0 (± standard deviation [SD] 138.9) to 61.3 (± SD 32.6) IU/L and 151.0 (± SD 86.9) to 46.1 (± SD 22.5) IU/L, respectively. Conclusions: Our initial observation seems to indicate the potential benefit of ABM extract in normalizing liver function of patients with hepatitis B. Controlled studies with larger samples should be conducted in the future.

Agaricus blazei Murill to improve side effects caused by anticancer drugs.

5. Okamoto T.
Current Topics in Pharmacology 2007;11(2):27-30

Agaricus blazei Murill (Himematsutake) was found in the south-east Brazil and introduced to Japan. Although A. blazei is frequently used for cancer treatment, it is not known whether A. blazei is effective or not for cancer. Therefore it is important to provide proper information which help to understand its efficacy in man. Antitumor and antimetastatic activities of A. blazei were shown by different types of tumor bearing mice models in vivo. Although effects are weak, A. blazei possesses anti-inflammatory and antidiabetic activities. In F344 rat, its subchronical safety was proved by 90 days ingestion of 5% A. blazei extract containing diet. In dimethylnitrosamine induced hepatocarcinogenesis in rat, post administration of A. blazei did not block promoter step, indicating that A. blazei may not a multipotential and broad-spectrum edible item for cancer prevention. Furthermore, some studies in human indicate ineffectiveness of A. blazei to promote cancer cell elimination by chemotherapy. However, the same studies suggest beneficial effect of A. blazei to improve anorexia, vomiting and insomnia caused by chemotherapy. In conclusion, A. blazei is suitable not for elimination of cancer cells, but for reduction of adverse effects caused by chemotherapy in man.

Measuring perceived effects of drinking an extract of basidiomycetes Agaricus blazei murill: A survey of Japanese consumers with cancer.

6. Talcott JA, Clark JA, Lee IP.
BMC Complementary and Alternative Medicine 2007;7

Background: To survey cancer patients who consume an extract of the Basidiomycetes Agaricus blazei Murill mushroom (Sen-Sei-Ro) to measure their self-assessment of its effects and to develop an instrument for use in future randomized trials. Methods: We designed, translated and mailed a survey to 2,346 Japanese consumers of Sen-Sei-Ro self-designated as cancer patients. The survey assessed consumer demographics, cancer history, Sen-Sei-Ro consumption, and its perceived effects. We performed exploratory psychometric analyses to identify distinct, multi-item scales that could summarize perceptions of effects. Results: We received completed questionnaires from 782 (33%) of the sampled Sen-Sei-Ro consumers with a cancer history. Respondents represented a broad range of cancer patients familiar with Sen-Sei-Ro. Nearly all had begun consumption after their cancer diagnosis. These consumers expressed consistently positive views, though not extremely so, with more benefit reported for more abstract benefits such as emotional and physical well-being than relief of specific symptoms. We identified two conceptually and empirically distinct and internally consistent summary scales measuring Sen-Sei-Ro consumers' perceptions of its effects, Relief of Symptoms and Functional Well-being (Cronbach's alpha: Relief of Symptoms, α = .74; Functional Well-Being, α = .91). Conclusion: Respondents to our survey of Sen-Sei-Ro consumers with cancer reported favorable perceived effects from its use. Our instrument, when further validated, may be a useful outcome in trials assessing this and other complementary and alternative medicine (CAM) substances in cancer patients.

The mushroom Agaricus blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: A randomized, double-blinded, and placebo-controlled clinical trial.

7. Hsu CH, Liao YL, Lin SC, Hwang KC, Chou P.
Journal of Alternative and Complementary Medicine 2007;13(1):97-102

Background: Complementary and alternative medicine use in adults with type 2 diabetes is popular. Although most of the herbs and supplements appear to be safe, there is still insufficient evidence that demonstrates their definitive beneficial effects. This study was done to determine whether the supplement of Agaricus blazei Murill extract improves insulin resistance in type 2 diabetes. Materials and Methods: This study was a clinical randomized, double-blind, placebo-controlled trial. Of a population of 536 registered diabetes patients with 72 subjects (1) aged between 20 and 75 years, (2) being Chinese, (3) having type 2 diabetes for more than 1 year, and (4) having been taking gliclazide and metformin for more than 6 months were enrolled in this study. The enrolled patients were randomly assigned to either receiving supplement of Agaricus blazei Murill (ABM) extract or placebo (cellulose) 1500 mg daily for 12 weeks. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as the major outcome measurement. Results: At the end of the study, subjects who received supplement of ABM extract (n = 29) showed significantly lower HOMA-IR index (3.6[standard deviation, 2.5] versus 6.6[standard deviation, 7.4], p = 0.04) than the control group (n = 31). The plasma adiponectin concentration increased 20.0(standard deviation, 40.7)% in the ABM group after 12 weeks of treatment, but decreased 12.0(20.0)% among those taking the placebo (p < 0.001). Conclusions: Supplement of ABM extract improves insulin resistance among subjects with type 2 diabetes. The increase in adiponectin concentration after taking AMB extract for 12 weeks might be the mechanism that brings the beneficial effect. Studies with longer periods of follow-up should be conducted in the future.

An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients.

8. Mukai H, Watanabe T, Ando M, Katsumata N.
Japanese Journal of Clinical Oncology 2006;36(12):808-10

Agaricus blazei (Himematsutake) extract, one of the most popular complementary and alternative medicines among Japanese cancer patients. In one patient, liver functions recovered gradually after she stopped taking the Agaricus blazei, but she restarted taking it, which resulted in deterioration of the liver function again. The other patients who were admitted for severe liver damage had started taking the Agaricus blazei several days before admission. Although several other factors cannot be completely ruled out as the causes of liver damage, a strong causal relationship between the Agaricus blazei extract and liver damage was suggested and, at least, taking the Agaricus blazei extract made the clinical decision-making process much more complicated. Doctors who are aware of their patients taking the extract may accept it probably because they believe there is no harm in a complementary and alternative medicine. When unexpected liver damage is documented, however, doctors should consider the use of the Agaricus blazei extract as one of its causal factors. It is necessary to evaluate many modes of complementary and alternative medicines, including the Agaricus blazei extract, in rigorous, scientifically designed and peer-reviewed clinical trials.

Effect of extracts squeezed from Agaricus blazei for high-normal blood pressure or mild hypertension on human blood pressure.

9. Inatomi S, Ouchi K, Adumi Y, Kobayashi H, Tsuchida T.
Japanese Pharmacology and Therapeutics 2006;34(12):1295-309

Extracts squeezed from Agaricus blazei fruits-body (ABFE) contain γ-aminobutyric acid (GABA), which expect hypotensive effects in hypertensive persons. We investigated hypotensive effects of A-extract in a double blind trial, 134 adults (averaged 48 years old) with high-normal blood pressure or mild hypertension. The amount of GABA in A-extract prepared 4 groups, which contain placebo (A group), 20mg GABA/ 50mL ABFE (B group), 40mg GABA/50mL ABFE (C group) and 70mg GABA/50mL ABFE (D group). All subjects were administrated once dairy for 8weeks. The results revealed that C group significantly decreased diastolic blood pressure (DBP) at 8 weeks in comparison with A group. C group significantly decreased systolic blood pressure (SBP) at 6 and 8 weeks and DBP at from 4 to 8 weeks in comparison with A group. D group significantly decreased systolic blood pressure (SBP) at 6 and 8 weeks and DBP at from 2 to 8 weeks in comparison with A group. B and D group increased blood pressure after finished administration of ABFE at once. Furthermore, subjective symptom, objective symptom, and blood examination were not observed in all subjects. These results of this study suggested that ABFE has hypotensive effects in adults with high-normal and mild hypertension, and optimal concentration of GABA is 40mg GABA/50mL ABFE.

The safety of excessive ingestion of Agaricus blazei in high-normal blood pressure persons.

10. Inatomi S, Ohuchi K, Adumi Y, Kobayashi H, Enoki R, Tsuchida T, Kanematsu T.
Japanese Pharmacology and Therapeutics 2006;34(12):1311-21

Agaricus blazei which is containing γ-aminobutyric acid (GABA), is expected lower blood pressure of a person of high blood pressure. To study the safety of extracts squeezed from A. blazei fruit-body (ABFE), we examined 25 high-normal blood pressure persons that were 30-65 years old (19 males and 6 females). All subjects were taken 150mL/ day (3 times of the normal) of ABFE for 4 weeks. Both systolic blood pressure and diastolic blood pressure decreased significantly after two weeks for ABFE oral administration. Then those blood pressures gradually increased without ABFE oral administration. All cases did not admit abnormality in a physique index, blood pressure, heartbeats, bloody chemical inspection, bloody general inspection and urine test for the result and all examination period. No abnormal clinical findings were observed from interviews in all subjects. These results suggested that oral administration ABFE of 150mL at a daily for 4 weeks is safe in high-normal blood pressure persons.

The safety of normal and excessive ingestion of Agaricus blazei in healthy persons.

11. Enoki R, Inatomi S, Ouchi K, Adumi Y, Mashiko K.
Japanese Pharmacology and Therapeutics 2006;34(11):1247-57

Agaricus blazei which is the native fungi in Brazil, is cultivated in the world and is known to be healthy foods. To study the safety of extracts squeezed from A. blazei fruit-body, we examined 30 healthy persons that were 40-60 years old (14 males and 16 females, averaged age 46.4). The subjects were divided into two groups, one group was taken 50 mL/day (the amount of normal during a day) of A. blazei extracts and the other group was taken 150 mL/day (3 times of the normal) of it for 4 weeks. No abnormal clinical findings were observed from the physical examination, blood analysis and interviews in all subjects. These results suggested that A. blazei extracts of 50-150 mL at a daily is safe in healthy persons.

Hypotensive effects and safety of extracts squeezed from Agaricus blazei on high-normal blood pressure and mild hypertensive subjects.

12. Kobayashi H, Inatomi S, Ouchi K, Adumi Y, Tsuchida T.
Japanese Pharmacology and Therapeutics 2006;34(12):1323-41

To investigate hypotensive effects and safety in the long term ingestion of extracts squeezed from Agaricus blazei (ABFE) containing γ-aminobutyric acid (GABA) which is expected hypotensive effect in hypertensive persons, we conducted double-blind, placebo-controlled study on high normal blood pressure and mild hypertensive subjects to the number of 80 (mean age, 46). Group A (n = 40) ingested 50mL of placebo water non-containing GABA as placebo-control, and group B (n = 40) ingested 50mL of ABFE containing 40mg of GABA for 12 weeks consecutively. In group B, systolic blood pressures of high normal blood pressure subjects decreased significantly at 4 weeks after ingest initiation compared with that of group A (p ~ 0.01), and diastolic blood pressure decreased significantly at 8 weeks after ingest initiation compared with that of group A (p < 0.01). In mild hypertensive subjects of group B, both systolic and diastolic blood pressures decreased significantly at 6 weeks or 4weeks after ingest initiation compared with those of group A, respectively (p < 0.05, p < 0.01, respectively). Furthermore, when the ABFE ingestion was stopped at 12 weeks after ingest initiation, systolic and diastolic blood pressures of all subjects in the group B were increased gradually. In addition, abnormalities in subjective symptom, interview by medical doctors, blood test, biochemical test and urinary test were not observed in all of subjects during the study period. These results suggest that the ABFE containing 40 mg of GABA causes reduction of systolic and diastolic blood pressures of high normal blood pressure and mild hypertensive persons in the long-term ingestion, and the ABFE is safety food.

Effects on gene expression and viral load of a medicinal extract from Agaricus blazei in patients with chronic hepatitis C infection.

13. Grinde B, Hetland G, Johnson E.
International Immunopharmacology 2006;6(8):1311-4

Extracts from the mushroom Agaricus blazei Murill (AbM) are used extensively as a non-prescription remedy against cancer and infections, including hepatitis. We previously demonstrated a potent immunomodulating effect of a particular preparation on monocytes in vitro, and a protective effect on bacterial infections in mice. Here we report the effect on gene expression in peripheral blood cells from four chronic hepatitis C patients, using global (29 k) oligo-based, single channel microarrays. The viral load was slightly, but not significantly, decreased after 1 week of AbM treatment. The cytokine genes most strongly induced in vitro were not induced in vivo. The more notable changes in mRNA levels were related to genes involved in the G-protein coupled receptor signalling pathway, in cell cycling, and in transcriptional regulation. The results suggest that the β-glucans of the extract, which presumably are responsible for cytokine induction, did not readily enter the blood, while other components, such as substances proposed to have anticancer effects, were active in the blood.

The safety of extended consumption of freezing dryness Agaricus blazei (Iwade strain 101) Himematsutake.

14. Kajimoto O, Ikeda Y, Yabune M, Sakamoto A, Kajimoto Y.
Japanese Pharmacology and Therapeutics 2006;34(1):103-17

We investigated the safety of "Freezing dryness Agaricus blazei (Iwade strain 101) Himematsutake" in a double-blind, placebo-controlled, parallel group study. The subjects were 46 adults with normal and slight hepatic function disorder who were not yet on medication (normal: 22 adults, slight hepatic function disorder: 24 adults). The subjects were divided into two groups at random. The treatment group was given the test food, and another group was given placebo food. They ingested each food (3g) twice a day for 12 weeks. We carried out inspection at the start day, after 2 weeks, 4 weeks, 8 weeks, 12 weeks, and more 4 weeks. As a result, there were no clinical problems in the blood examination, urinalysis, physical examination and history taking. These results demonstrate that "Freezing dryness Agaricus blazei (Iwade strain 101) Himematsutake" has no ill effects on the human body.

Use of complementary and alternative medicine by patients with urologic cancer: A prospective study at a single Japanese institution.

15. Yoshimura K, Ueda N, Ichioka K, Matsui Y, Terai A, Arai Y.
Supportive Care in Cancer 2005;13(9):685-90

We prospectively evaluated the prevalence and predictors of complementary medicine (CAM) use among Japanese patients with urologic cancer 1 year after diagnosis. Patients and methods: A total of 349 patients with newly diagnosed urologic cancer answered a self-administered questionnaire on CAM use 1 year after diagnosis. General-health-related quality of life (GHQL) of the patients was also assessed at diagnosis and 1 year after diagnosis using the Medical Outcome Study Short Form-36 (SF-36). The overall prevalence, types of CAM used, and costs of CAM were assessed. The effects of several variables including GHQL at baseline and 1 year after treatment on the prevalence of use of CAM were evaluated. Results: A total of 164 respondents (47%) admitted using some type of CAM, of which 73 (45%) had used multiple types. "Health food," in particular extract from Agaricus blazei, was the most common type of CAM used. CAM users had significantly lower scores for social function, general health perception, and vitality domains than CAM non-users 1 year after diagnosis. This tendency was more marked in users of multiple types of CAM. Conclusions: "Health food," including extract from A. blazei, was the most commonly used CAM in Japan. The prevalence of CAM use did not differ between patients with prostate cancer and those with urologic cancer other than prostrate cancer. CAM users, especially those who used multiple types of CAM, had lower GHQL scores than non-users of CAM.

Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy.

16. Ahn WS, Kim DJ, Chae GT, Lee JM, Bae SM, Sin JI, Kim YW, Namkoong SE, Lee IP
International Journal of Gynecological Cancer 2004;14(4):589-94

A mushroom extract, Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and antitumor effects. Here, we investigate the beneficial effects of ABMK consumption on immunological status and qualities of life in cancer patients undergoing chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated either with carboplatin (300 mg/m2) plus VP16 (etoposide, 100 mg/m2) or with carboplatin (300 mg/m2) plus taxol (175 mg/m2) every 3 weeks for at least three cycles with or without oral consumption of ABMK. We observed that natural killer cell activity was significantly higher in ABMK-treated group (ANOVA, n = 39, P < 0.002) as compared with nontreated placebo group (n = 61). However, no significant difference in lymphokine-activated killer and monocyte activities was observed in a manner similar to the count of specific immune cell populations between ABMK-treated and nontreated groups. However, chemotherapy-associated side effects such as appetite, alopecia, emotional stability, and general weakness were all improved by ABMK treatment. Taken together, this suggests that ABMK treatment might be beneficial for gynecological cancer patients undergoing chemotherapy.

Lowering effects in plasma cholesterol and body weight by mycelial extracts of two mushrooms: Agaricus blazai and Lentinus edodes.

17. Kweon MH, Kwon ST, Kwon SH, Ma MS, Park YI.
Korean Journal of Microbiology and Biotechnology 2002;30(4):402-9

The effects of protein-bound polysaccharides (A-PBP and L-PBP) that were extracted from the mycelia of two edible mushrooms, namely Agaricus blazai and Lentinus edodes, on serum cholesterol and body weight were investigated in mice and female volunteers. Six groups of Male Balb/c mice were fed six kinds of diet supplement-solutions composed of L-PBP, A-PBP, chitosan, and other fiber constituents, for 30 days under the normal diet. Ninety female volunteers were also supplemented for 8 weeks with six kinds of capsules including control and five test groups as the same manners (two times a day, 4 capsules). From 12 days after feeding of L-PBP (Group I) and A-PBP (Group II), the weight of mice began to reduce as compared with control, whereas that of Group III fed chitosan was decreased 15 days after feeding. Group IV and Group V, which were fed mixture of L-PBP, A-PBP, chitosan, and other dietary fiber, were more significant in lowering weight. After 4 weeks of the supplementation in women, their serum LDL-cholesterol level and body weights in Group I and II were reduced, but Group III taken with chitosan capsule showed weaker effect than Group I and II. After 8 weeks, LDL-cholesterol content in the sera of Group I (132.5 mg/ dL) and II (131.5 mg/dL) was decreased to ideal level (125.4 and 122.8 mg/dL) for healthy blood vessel. In the case of Group IV supplemented with mixture of L-PBP, A-PBP, and chitosan, the weight-reduction effect (11.8%) and hypocholesterolemic effect (11.0%) was most significant, indicating their synergistic action. These data suggested that the weight-controlling and hypolipidemic effect of L-PBP and A-PBP was involved, at least in part, in absorption of cholesterol as their role of dietary fiber, as well as cholesterol metabolism.

Clinical utility of ABCL (Agalicus Mushroom Extract) treatment for C-type hepatitis.

18. Inuzuka H, Yoshida T.
Japanese Pharmacology and Therapeutics 2002;30(2):103-7

The aims of present study are to investigate the clinical effects and safety evaluation on human volunteers with elevated γ-GTP activity for Agaricus Blazei Condensed Liquid (Agaricus Mushroom Extract; ABCL). Agaricus extracts have various physiological active substances such as β-glucan protein complex, and various other polysaccharides. Specially, β-glucan activates cellular immunological system of macrophages and/or lymphocytes and stimulates secretion of various cytokines. A total of 20 patients (50% of men) with chronic C-type hepatites received the ABCL orally twice a day for 8 weeks. Clinical decreasing effect for serum γ-GTP activity was found in 80% of the patients in both sexes. The toxicological findings and other side effects were not observed at all. From these results, it is considered that the ABCL is useful for patients with light hepatopathy such as C-type hepatitis.