Maitake Mushroom: a novel immune enhancer

Maitake Mushroom: a novel immune enhancer

Harry Preuss

Background

Throughout much of the world, extracts derived from maitake and other mushrooms are considered to be frontline medical “drugs,” even though the scientific study of mushrooms has only begun during the last 20 years. (1-6) Some mushrooms are rich in minerals (potassium, calcium, and magnesium), various vitamins (D2, B2, niacin, and C), and amino acids, but perhaps the most important ingredients found in maitake are polysaccharide compounds called beta-glucans that exhibit strong immune support activity. (7-25) The maitake mushroom, indigenous to the northeastern part of Japan, is an especially rich source of beta-glucans. (7,13,17) For hundreds of years, indeed for 3000 years, this rare mushroom has been prized in China and Japan not only for it delicious taste but for its health benefits. Common lore states that maitake is so named because people who found it in the deep mountains knew of its luscious flavor and health benefits and thus began dancing with joy. In the feudal era of Japan, the mushroom was excha nged for the same weight of silver by local lords who, in turn, offered it to the shoguns. The botanical name of maitake is Grifola frondosa, a designation that refers to a mythical beast — half-lion and half-eagle.

Beta-Glucans: An Introduction

Today, many mushrooms are being recognized for their important health benefits. This is primarily because they are an excellent source of beta-glucan polysaccharide compounds that promote well-being. (3) Beta-glucans (also known as [beta]-l,3/1,6-D-glucan or beta1,3/1 ,6-glucan) are non-digestible polysaccharides (long chain carbohydrates) found in the cell walls of maitake mushroom. As with any beta-glucan (or poly-glucose), its [beta]-1,3/1,6-D-glucan consists of multiple glucose units linked together. While common table sugar, a dimer composed of glucose and fructose, may be deleterious to health when consumed in excess, beta-glucans are healthful. Indeed, we need small amounts of beta-glucans for our bodies to function properly. However, these are no longer abundant and scarcely present in our limited, over-processed diets.

Immune Enhancing Functions of Beta-Glucans

When beta-glucans are consumed prudently, one’s immune health benefits greatly. Individuals reactivate their immune system, regain their ability to fight disease, and are able to ward off infection. These complex sugars are the basis of multicellular immune intelligence — the ability of immune cells to communicate, cohere, and work together to keep us healthy and balanced.

How do they work? Beta-glucans have been shown to dock onto receptors on the outer cell walls of macrophages and activate them, so that they can aid us in our fight against cancer and infectious diseases. (26) Macrophages contain specific protein-based receptor complexes on their cell walls to which the [beta]-1,3/1,6-D-glucan molecule readily binds. The binding of [beta]1,3/1 ,6-D-glucan enhances their ability to detect and scavenge a variety of health threats. It may be truly stated that the body’s macrophages and beta-glucans were meant for each other. Bacterial infections respond remarkably to these polysaccharides, as do many viral infections from the common cold and flu to herpes and HIV. Beta-glucans even mitigate the toxic effects of radiation and chemotherapy while augmenting their cancer-killing effects, resulting in prolonged survival and improved quality of life for cancer patients. (1,2)

Many biological response modifiers stimulate nonspecific immunity. Among these are various synthetic and biological agents, each with completely different chemical structures. Herbs, such as astragalus, echinacea, and others, have been documented to possess a non-specific immunomodulatory effect. (27,28) In contrast, most of the medicinal mushrooms, such as reishi, shiitake, cordyceps, and maitake, show a common ability to enhance immune function by stimulating cell-mediated immunity. (29) Quite simply, mushrooms seem to turn on cells in the immune system, including macrophages and T-cells that appear to have significant cancer- and infection-fighting properties. It is important to note that while many fungi can be used as a source of beta-glucans, maitake is substantially differentiated from the others because it appears to retain efficacy when administered orally. To use an example, lentinan derived from shiitake must be administered intravenously to be most effective. (29) Accordingly, maitake is the most effective when compared to other mushrooms, can be taken orally, and is completely safe. Also worth noting is that other factors, in addition to specific beta-glucan fractions, present in the crude maitake powder offer many additional health benefits to consumers, including blood sugar control, lowering of cholesterol, high blood pressure reduction, and even aiding weight loss. (30-36)

Today, numerous studies have been conducted on various beta-glucans, and much information can be derived from them. Beta-glucans are classified by scientists as semi-essential, non-vitamin factors and are believed to protect against certain diseases. These polysaccharides are found in other “superfoods,” including oats, nutritional yeasts, and other medicinal mushrooms, but the chemical structures of maitake’s beta-glucans, especially those found in the D-fraction, are unique due to their greater degree of molecular branching. (6,7) People have known for a very long time that the Monkey’s Bench mushroom family, of which maitake is a member, possesses significant anti-cancer effects. Therefore, they have used the ingredients obtained by boiling these substances down as a sort of medicinal hot water treatment for certain cancers. It is now known conclusively that the anti-tumor effects are the result of the activity of various beta-glucans found in the mycelium (which is the mass of interwoven filaments that fo rm the vegetative portion of the maitake mushroom and are submerged in soil or organic matter). (14) Researchers obtained various fractions by continually refining down the elements in the fruiting body of maitake. The results of this research were first published in the l980s. (6-22)

It was the D-fraction of maitake extract, which was obtained last, that was found to possess the most potent anti-tumor activity, leading to the highest reduction rate in cancer proliferation. (1,2,37-41) Research on the beta-glucans found in the D-fraction of maitake has demonstrated effects on not only macrophages but also natural killer cells and various T-cells and demonstrates perhaps the highest cancer inhibition with oral administration of any source of beta-glucan. (8,10,20-22)

Mechanisms of Action of Beta-Glucans

No matter whether an infection is bacterial, viral, fungal, or parasitical, maitake’s beta-glucans have been known to effectively activate the immune system and enhance the body’s healing response. (1) Complementing antibiotics and chemotherapeutic agents, beta-glucans influence generalized immune enhancement by supporting a fundamental aspect of immune function — the workings of the primitive macrophage. Indeed, beta-glucans may be essential to optimal immune function for virtually all life forms. Meanwhile, more studies on various beta-glucans, all with similar configurations and derived from a variety of sources, continue to demonstrate an even broader array of therapeutic benefits. These include prevention and treatment of a wide variety of cancers, as well as protection against surgical-, chemotherapeutic- and radiation-induced side effects. A literature review on maitake confirms this natural medicine is an important adjuvant in cancer therapeutics for mitigating the damaging side effects of chemothera py and radiation, as well as for improving the body’s innate immune defenses and improving the main outcome — living cancer-free.

Another way that maitake’s beta-glucans may aid is by stimulation of tumor inhibitors. In certain experimental models, systemic macrophage activation and certain cytokine releases seem to be critical for clearing tissues of tumor cells and inhibiting metastasis. In 1995, Dr. Mitsuhiro Okazaki and co-researchers (43) demonstrated that maitake mushroom stimulates release of, or rather “primes” the body to release, tumor necrosis factor-alpha. Additional studies have corroborated that maitake is a potent, broad-spectrum cytokine inducer. In other words, maitake D-fraction exhibits an anti-tumor effect on tumor-bearing mice through both enhanced cytotoxic activity and stimulating the macrophages, thus helping them live up to their fullest potential. This enhanced activity of macrophages has resulted in elevated production of interleukin-1 and the resulting activation of cytotoxic T-lymphocytes and many additional cytokines.

Another focus of research shows that the D-fraction of maitake mushroom can inhibit metastasis of cancer cells. Cancer metastases were reduced to less than one-tenth with use of maitake D-fraction. (37,44) In a laboratory study, MM-164 liver cancer was injected into the left rear footpad of three groups of mice, and the footpad was surgically removed after 48 hours. The first group was given normal feed. The second group received 20% maitake powder in their feed. The third group received one milligram per kilogram maitake D-fraction with their feed. All three groups were then bred for another 30 days. The number of tumor metastases in the liver were counted by microscope. It was observed that metastases to the liver were prevented by 91% with Maitake D-fraction and by 81% with maitake crude powder at the doses administered relative to a control group.

Cancer researchers studied the conditions necessary for cancer metastasis and discovered one critical event is the growth of a new network of blood vessels. (1) Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. Tumor angiogenesis actually starts with cancerous tumor cells releasing molecules that send signals to surrounding normal host tissue. This signaling activates certain genes in the host tissue that, in turn, make proteins that encourage growth of new blood vessels. Maitake’s beta-glucans, by stimulating tumor necrosis factor, can prevent this process, at least to some extent.

Maitake D-fraction was observed to affect angiogenesis in vivo and to enhance the proliferation capability and migration capability of human vascular endothelial cell in vitro. The D-fraction also increased plasma vascular endothelial growth factor (VEGF) concentration significantly. Also, VEGF and TNF-alpha production by the activated peritoneal macrophages was enhanced. Thus, these results suggest that the anti-tumor activity of the D-fraction not only works via the activation of the immunocompetent cells but also possibly through inhibition of carcinoma angiogenesis induction.

Maitake and Beta-Glucans: Research on Health Benefits

In 1978, Mansell et al. (45,46) wrote about the use of beta-glucans for immune modulation and control of cancer as an adjuvant therapy. One of the most lethal cancers today is melanoma. Dr Mansell and colleagues showed that injection of [beta]-1,3-D-glucan into melanoma lesions led to successful regression. Examination of the site indicated extreme macrophage activity during the time that they engulfed and destroyed tumor cells. Use of injections also appeared to reduce the risk of the spread of the cancer. The size of the large cancer lesions was markedly reduced in just five days, and in small lesions, resolution was complete.

A 1980 experimental study from the Department of Physiology at Tulane University School of Medicine, New Orleans, Louisiana, also demonstrates that beta-glucans may inhibit the growth of these cancers. (47) Maitake may also enhance apoptosis of tumor cells. (48) Beta-glucan injections decreased tumor weight by about 70% in mice with melanoma and inhibited spread of the cancer to the lungs. The researchers found that beta-glucans were effective in prolonging survival of mice with melanoma.

In other published studies, maitake D-fraction has been shown to benefit persons suffering from cancers of the pancreas, brain, prostate, liver, lung, and breast either by decreasing or stabilizing tumor size, reducing tumor markers, or by prolonging patients’ expected lifespan by more than fourfold. (2,41) For example, Chinese researchers from Zhejiang Medical University and Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China, used maitake extract on 63 cancer patients as adjuvant therapy with their chemotherapy and radiation treatments. (49) The patients took the maitake extract before meals, four times per day. The results were highly gratifying, with a 96% success rate against solid tumors and 91% among the leukemia patients. The total effective rate for overall immune enhancement was estimated by the researchers at 87%.

In a non-randomized clinical study, 165 patients aged 25-65 and diagnosed with various stages III-IV cancers were given maitake D-fraction with crude maitake powder tablets only or with chemotherapy. (2,41) Tumor regression or significant improvements were observed among 11 out of 15 breast cancer patients, 12 out of 18 lung cancer patients, and 7 out of 15 liver cancer patients. If taken with chemotherapy, these response rates improved by 12-28%. In several cases with both liver and lung cancer, the patients went from dangerous stage III status to more manageable stages.

Effects of Maitake on Side Effects of Chemotherapy

The use of the maitake D-fraction also ameliorated various side effects due to chemotherapy, such as lost appetite, vomiting, nausea, hair loss, and white blood cell deficiency in 90% of patients; pain was reduced in 83%. (25) There are also strong indications that while the extract contributes to tumor reduction without a high loss of white blood cells, it also reduces pain, hair loss, nausea, and other side effects usually associated with chemotherapy as a cancer treatment.

Summary and Conclusions

What makes maitake and its fractions so special among providers of beta-glucans? For one thing, maitake has been studied more extensively than other beta-glucan providers, allowing one to examine concrete data. Also, the beta-glucans obtained from maitake mushrooms have unique, complex, and varied chemical structures. A three dimensional model of maitake’s [beta]-1,3-D-glucan shows it to be a helix with its 1,6 main chain having a greater degree of 1,3 branches. (6,12-14) It can be postulated that this greater degree of branching provides its beta-glucans more chance to reach each immune cell for activation, and thus gives it greater potency. Many beta-glucans found in this natural medicine have a (1[right arrow]6) branch in every other main chain unit. Others have two (1[right arrow]6) branches in every third main chain unit. In studies on structure-activity relationships of beta-glucan-mediated immunopharmacological activity, it was found that some of the activities tested are influenced by the diversity of the beta-glucans. The maitake D-fraction activates macrophages, natural killer cells, and other T-cells to attack the tumor cells. While the beta-glucans in D-fraction potentiate the activity of various mediators, mainly lymphokines and interleukin-1 and interleukin-2, other beta-glucan fractions obtained from maitake and different sources have completely different activities. (50)

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About the Author

Dr. Preuss is a graduate of Cornell Medical School in New York City, trained for three years in internal medicine at Vanderbilt University Medical Center, spent two years as a fellow in renal physiology at Cornell University Medical Center, and two more years in clinical and research training in nephrology at Georgetown University Medical Center. He then worked as an Assistant and Associate (tenured) Professor at the University of Pittsburgh Medical Center for five years. He is currently Professor of Physiology, Medicine, and Pathology (tenured) at Georgetown University Medical Center. His bibliography includes nearly 500 medical articles. Dr. Preuss has edited or co-edited four books and two symposia published in well-established journals. He is the co-author of a book written for the lay-public The Prostate Cure. He was a special research fellow of the NIH in 1966 and an Established Investigator of the American Heart Association from 1967-1972. In 1976, Dr. Preuss was elected to membership in the American S ociety of Clinical Investigations, a prestigious research group. He has had numerous grants from the NIH, USDA, and AHA. He is currently an advisory editor for six journals. His previous government appointments included four years on the Advisory Council for the National Institute on Aging, two years on the Advisory Council of the director of the NIH (Wyngaarden), and two years on the Advisory Council for the Office of Alternative Medicine of the NIH He has been a member of many other peer research review committees for the NIH and American Heart Association and was recently appointed to membership on the National Cholesterol Education Program at the NHLBI. Dr. Preuss has been invited as a featured speaker at many meetings and has participated in discussions concerning nutrition on audio and video

Maitake Mushroom

tapes, as well as live television. Dr. Preuss has held many important posts in the American College of Nutrition and is a past president. He was recently elected the ninth Master of the American College of Nutrition. Dr. Preuss is a member of the board of directors for the American Preventive Medical Association and is on the medical advisory board of Advocare, Inc., of Dallas, Texas, and the Alzheimer’s Prevention Foundation. He has consulted for Novartis Pharmaceuticals (Summit, New Jersey), Alternet Health Technologies (Los Angeles, California), and InterHealth Neutraceuticals (Benicia, California). Dr. Preuss wrote the nutrition section for the Encyclopedia Americana and was recently elected president of the Certification Board for Nutrition Specialists (CBNS) which gives the CNS certificaton. He is now Co-Chairman of the Internal Review Board, which reviews all clinical protocols at Georgetown University Medical Center.

Dr. Bagchi received his PhD in Medicinal Chemistry in 1982. He conducted postdoctoral research on free radicals and antioxidants at the University of Connecticut School of Medicine, Farmington, Connecticut. Presently he is an Adjunct Associate Professor in the Creighton University School of Pharmacy and Allied Health Professions, Omaha, Nebraska; a Visiting Associate Professor of Toxicology in the Arnold and Marie Schwartz College of Pharmacy and Allied Health Sciences, Long Island University, Brooklyn, New York; and the Director of Research and Development of Inter Health Nutraceuticals, Concord, California. His research interests include free radicals, human diseases and the protective role of antioxidants. Dr. Bagchi is actively engaged in assessing the intricate issues of cell death and the mechanistic pathways of antioxidant cytoprotection.

Dr. Bagchi has 106 papers on free radicals and antioxidants in peer reviewed journals. He has delivered lectures at various national and international conferences. Dr. Bagchi is a Fellow of the American College of Nutrition, Member of the Society of Toxicology, Member of the New York Academy of Sciences, and a Member of the TCE Stakeholder Committee of the Wright Patterson Air Force Base, Ohio. He has been inducted into the Phi Beta Delta Honor Society for International Scholars. Very recently, Dr. Bagchi has been appointed as a member of the Study Section and Peer Review Committee of the National Institutes of Health, Bethesda, Maryland

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