The Medicinal Mushroom for Cellular Immune Protection
The The maitake mushroom (Grifola frondosa) is the source of immune enhancing compounds that are being shown to offer significant health benefits.1,2 The commercial evolution of maitake has led to the development of Maitake Gold 404™, a proprietary maitake extract developed by Dr. Hiroaki Nanba – the world’s leading authority on maitake.
In the early 1980s, Dr. Nanba was researching the immune enhancing properties of mushrooms when he came to the conclusion that maitake extracts demonstrated more pronounced antitumor activity in animal tests than other mushroom extracts.3* One of the key benefits to maitake was the ability to be quite effective when given orally. In contrast, the other mushrooms Dr. Nanba was studying such as shiitake were only effective when injected into the bloodstream.
In 1984, Dr. Nanba identified a fraction of maitake that possessed a significant ability to stimulate white blood cells known as macrophages (literal translation “big eaters”).These specialized white blood cells phagocytize or engulf foreign particles including cancer cells, bacteria, and cellular debris. Dr. Nanba termed his discover maitake D-fraction.This fraction consisted of polysaccharide compounds (beta-1,6 glucan and beta-1,3 glucan) and protein. In 1984 a patent was issued in Japan to Nanba and others.
While other medicinal mushrooms have shown to have similar beta-glucan constituents, Dr. Nanba found that the beta-glucans found in the maitake D-fraction have a unique and complex structure.The biggest difference was a greater number of branching side chains. It is thought that the greater the degree of branching, the higher the likelihood the beta-glucan fraction will reach and activate a greater number of immune cells.4-6
Throughout the late 1980s and into the 1990s, Dr. Nanba and other Japanese researchers continued to study maitake, trying to improve upon the antitumor and immunopotentiating activity of the Dfraction. Further purification of the D-fraction yielded the MD-fraction (U.S. Patent #5,854,404), which is even more bioactive than the D-fraction.7 It is important to point out that any research references to the D-fraction also apply to the purer and more potent MD-fraction (i.e., Maitake Gold 404™). The MD-fraction is produced in a similar manner to the D-fraction; however, Dr. Nanba added a key step that removes some impurities found in the D-Fraction.7 The result is that the MD-fraction provides superior results over the D-fraction. For example, in an antitumor test described in the patent each solution was administered to mice with carcinomas.The researchers found the group given the MD-fraction experienced a significantly stronger inhibitory effect on tumor growth than that of the group given the D-fraction.The researchers also compared each fraction’s effects on white blood cells (macrophage and killer T-cell activity) five days after each test substance was given.The MD-fraction also exhibited stronger immune system potentiation compared to the D-fraction. Both the D- and MD-fractions are considered to have low toxicity and high safety.
What are the other effects of maitake beta-glucan fractions on the immune system and how does it fight cancer?
Maitake beta-glucan fractions exert profound effects on immune function.6,8-12* In a nutshell, it appears that the beta-glucans in the maitake MD-fraction actually bind to receptors on the outer membranes of macrophages and other white blood cells including natural killer (NK) cells and cytotoxic T-cells (Tc). These immune cells are very important in protecting against and fighting cancer because they can attack tumor cells directly.*
Just like a key in a lock, the binding of the beta-glucan literally flips white blood cells on and triggers a chain reaction leading to increased immune activity. In addition to increasing the ability of the macrophages to engulf and destroy cancer cells, microbes, and other foreign cells, the beta-glucan binding stimulates the production of important signaling proteins of the immune system such as interleukin-1 interleukin-2, and lymphokines. These immune activators ramp up defenses by activating immune cells.
Beta-glucans from Maitake Gold 404™ also stimulate the production of white blood cells within the bone marrow – the major area for white blood cell production. Reduced bone marrow production means lowered white cell counts and an increased risk of infection and cancer. This beneficial effect of the beta-glucan is put to good use in cancer patients undergoing radiation therapy or chemotherapy.
Do other sources of beta-glucans provide the same benefit as MaitakeGold 404™?
Beta-glucans are found in many other forms. However, the unique branching pattern of maitake MD-fraction makes it the ideal source of these molecules. Beta-glucans from oats and barley, for example, tend to form viscous gel. When consumed with a meal, oat and barley beta-glucans act as a good source of soluble fiber in lowering cholesterol and blood sugar levels, but they really don’t have much of an impact on the immune system. Purified beta-glucans from the common baker’s yeast (Saccharomyces cerevisiae) possess similar benefit to maitake beta-glucan fractions, but may not be as well absorbed.
How does maitake beta-glucan fractions inhibit tumor growth?
Maitake researchers have identified four primary mechanisms by which maitake fights cancer:13-21
- By protecting healthy cells from becoming cancerous.*
- By enhancing the immune system’s ability to seek out and destroy cancer cells.*
- By helping the cell regain control of cell division and programmed cell death (apoptosis).*
- By helping to prevent the spreading (metastasis) of cancer.*
Another way in which maitake beta-glucan fractions may inhibit cancer formation is via enhancement of apoptosis, a distinct form of cell death controlled by an internally encoded suicide program.22* In cancerous cells, there is a tendency of suppression of this natural process of cell death. Instead of dying, the cancer cell multiplies. By promoting apoptosis, cancer cells can literally be turned off.
Does maitake have any benefit against the human immunodeficiency virus (HIV)?
Yes. In the late 1980s, Japanese researchers determined maitake D-fraction enhanced helper Tcells, the target cells of HIV.26* This was one of the earliest clinical indications that maitake may be a potential treatment for HIV. Since then, test tube studies have shown some promising results in inhibiting HIV. Recently, the effect of the MDfraction was studied in 35 HIV-positive subjects for 360 days.27 The researchers monitored helper T-cell (CD4+) counts, viral load, symptoms of HIV infection, status of secondary disease, and subjects’ sense of well-being. Effects on the helper T-cell count and viral load were variable: helper Tcells increased in 20 patients, decreased in eight patients, and remained static in four patients. Viral load decreased in ten patients, increased in nine patients, and was static in two patients. The big change was that 85% of the patients reported an increased sense of well-being with regard to various symptoms and secondary diseases caused by HIV. The researchers concluded that the MD-fraction appears to work on several levels: by direct inhibition of HIV, stimulation of the body’s own natural defense system against HIV, and making the body less vulnerable to opportunistic disease.33
Can maitake betaglucan fractions be used during chemotherapy?
According to preliminary data, maitake betaglucan fractions appear to help reduce the side effects of conventional chemotherapy (and radiation) while at the same time enhancing its effectiveness. 23* In 1994, a group from China published findings from a pilot study on 63 cancer patient reporting a total effective rate against solid tumors at higher than 95% and the effective rate against leukemia higher than 90%. In a preliminary study conducted by Dr. Nanba, 165 patients with advanced cancer were given maitake extract.24 In the patients who were also on chemotherapy, 90% of the patients experienced a reduction in the side effects common to chemotherapy including hair loss, decreased white blood cell counts, nausea, vomiting, and loss of appetite. Maitake was shown to effectively reduce pain levels in 83% of the patients. The results were best in breast, lung, and liver cancers. Dr. Nanba reported significant improvement in symptoms or regression of tumors in 73.3% of patients with breast cancer, 66.6% in lung cancer, and 46.6% in liver cancer. In contrast to the incredible response rates claimed in the Chinese study, in Dr. Nanba’s study less than 50% of the leukemias and cancers of the prostate, brain, stomach, and bone seemed to respond.
These preliminary studies need to be followedup by larger, better controlled studies. It appears that such studies are on the horizon as in February 1998 the U.S. Food and Drug Administration approved an Investigational New Drug Application (IND 54,589) for researchers to conduct a more detailed pilot study on maitake D-fraction’s potential effects on advanced breast and prostate cancers.
What type of tumors are inhibited by maitake beta-glucan fractions?
Preliminary studies in animal models have shown maitake fractions inhibit the growth of tumors in the colon, lungs, stomach, liver, prostate, cervix, bladder, and brain, as well as leukemia.* The significance of this inhibition in animal models to the human condition is not clear at this time, but it does give us an idea of the potential of maitake beta-glucan fractions.
What is the proper dosage for Maitake Gold 404™?
The dosage of maitake extracts is based upon the level of the D- or MD-fraction. The therapeutic dosage range is based upon body weight, 0.5mg to 1.0 mg for every 2.2 pounds (1 kg) of body weight per day. That translates to a dosage of approximately 35-70 mg of the D- or MD-fraction. The dosage recommendation for prevention is typically 5 to 15 mg of the D- or MD-fraction. For best results take 20 minutes before meals or on an empty stomach.
- Mayell M. Maitake extracts and their therapeutic potential. Altern Med Rev 2001;6:48-60
- Jones K. Maitake: a potent medicinal food. Alt Comp Ther 1998;4:420-429.
- Nanba H, Hamaguchi A, Kuroda H.The chemical structure of an antitumor polysaccharide in fruit bodies of Grifola frondosa (maitake). Chem Pharm Bull 1987;35:1162-1168.
- Adachi Y, Ohno N, Ohsawa M, et al. Change of biological activities of (1-3)-beta-D-glucan from Grifola frondosa upon molecular weight reduction by heat treatment. Chem Pharm Bull 1990;38:477-481.
- Okazaki M, Adachi Y, Ohno N,Yadomae T. Structure-activity relationship of (1Ñ>3)-beta-D-glucans in the induction of cytokine production from macrophages, in vitro. Biol Pharm Bull 1995;18:1320-1327.
- Borchers AT, Stern JS, Hackman RM, et al. Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med 1999;221:281-293.
- Nanba H, Kubo K. Antitumor substance extracted from Grifola. U.S.Patent 5,854,404, issued December 29, 1998.
- Adachi Y, Okazaki M, Ohno N,Yadomae T. Enhancement of cytokine production by macrophages stimulated with (1Ñ>3)-beta-D-glucan, grifolan (GRN), isolated from Grifola frondosa. Biol Pharm Bull 1994;17:1554-1560.
- Adachi Y, Ohno N,Yadomae T. Activation of murine kupffer cells by administration with gel-forming (1Ñ>3)-beta-D-glucan from Grifola frondosa. Biol Pharm Bull 1998;21:278-283.
- Ohno N, Egawa Y, Hashimoto T, et al. Effect of beta-glucans on the nitric oxide synthesis by peritoneal macrophage in mice. Biol Pharm Bull 1996;19:608-612.
- Suzuki I, Itani T, Ohno N, et al. Effect of a polysaccharide fraction from Grifola frondosa on immune response in mice. J Pharmacobiodyn 1985;8:217-226.
- Suzuki I, Hashimoto K, Oikawa S, et al. Antitumor and immunomodulating activities of a beta-glucan obtained from liquid-cultured Grifola frondosa. Chem Pharm Bull 1989;37:410-413.
- Yamada Y, Nanba H, Kuroda H. Antitumor effect of orally administered extracts from fruit body of Grifola frondosa (maitake). Chemotherapy 1990;38:790-796.
- Adachi Y, Ohno N, Ohsawa M, et al. Physiochemical properties and antitumor activities of chemically modified derivatives of antitumor glucan “grifolan LE” from Grifola frondosa. Chem Pharm Bull1989;37:1838-1843.
- Mizuno T, Ohsawa K, Hagiwara N, Kuboyama R. Fractionation and characterization of antitumor polysaccharides from maitake, Grifola frondosa. Agric Biol Chem 1986;50:1679-1688.
- Ohno N, Asada N, Adachi Y,Yadomae T. Enhancement of LPS triggered TNF-alpha (tumor necrosis factor-alpha) production by (1Ñ>3)-beta-D-glucans in mice. Biol Pharm Bull 1995;18:126-133.
- Suzuki I, Itani T, Ohno N, et al. Antitumor activity of a polysaccharide fraction extracted from cultured fruiting bodies of Grifola frondosa. J Pharmacobiodyn 1984;7:492-500.
- Takeyama T, Suzuki I, Ohno N, et al. Host-mediated antitumor effect of grifolan NMF-5N, a polysaccharide obtained from Grifola frondosa. J Pharmacobiodyn 1987;10:644-651.
- Ohno N, Adachi Y, Suzuki I, et al. Antitumor activity of a beta-1,3-glucan obtained from liquid cultured mycelium of Grifola frondosa. J Pharmacobiodyn 1986;9:861-864.
- Yang DA. Inhibitory effect of Chinese herb medicine zhuling on urinary bladder cancer. An experimental and clinical study. Chung Hua Wai Ko Tsa Chih 1991;29:393-395,399.
- Suzuki I,Takeyama T, Ohno N, et al. Antitumor effect of polysaccharide grifolan NMF-5N on syngeneic tumor in mice. J Pharmacobiodyn 1987;10:72-77.
- Fullerton SA, Samadi AA,Tortorelis DG, et al. Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide). Mol Urol 2000;4:7-13.
- Nanba H. Maitake D-fraction: healing and preventive potential for cancer. J Orthomol Med 1997;12:43-49.
- Nanba H. Results of non-controlled clinical study for various cancer patients using maitake D-fraction. Explore 1995;6:19-21.
- Nanba H, Kodama N, Schar D,Turner D. Effects of maitake (Grifola frondosa) glucan in HIV-infected patients. Mycoscience 2000;41:293-295.
- Hishida I, Nanba H, Kuroda H. Antitumor activity exhibited by oral administered extract from fruit body of Grifola frondosa (maitake). Chem Pharm Bull 1988;36:1819-1827.
- Nanba H, Kodama N, Shar D,Turner D. Effect of Maitake (Gifolia frondosa) glucan in HIV-infected patients. Mycoscience 2000;41:293-5.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.