A healthy immune system is required for rejuvenation. Yet, often it is the immune system itself that requires rejuvenating to bring it to a level where it can better support rejuvenation of the entire body. Our Rejuvenation Program therefore builds the immune system and includes supplement recommendations and supporting protocols to accomplish that goal. The most important immune building supplement we recommend is Immune-Assist™, a mushroom complex of six medicinal mushrooms containing polysaccharides that provide a wide range of health benefits.
Other important immune building supplements included in HPDI’s Master Rejuvenation program are echinacea, garlic, olive leaf extract, and astragalus. We will discuss immune strengthening using medicinal mushrooms and Immune-Assist™ in this article. Additional articles (forthcoming) will be dedicated to the other immune-building supplements.
Medicinal Mushrooms Extracts: One of the Most Powerful Immune Modulators
Recent scientific research has shown that medicinal mushrooms grown on vegetable sources (such as millet, rice bran, buckwheat, barley, etc.) enzymatically activate a process whereby complex cross-linked polysaccharides from the vegetable sources are converted to biologically active immunomodulators (also known as biological response modifiers). As you will see from the discussion below, the polysaccharides produced by this process are effective and safe immune stimulants.
Medicinal mushroom research has focused on discovering compounds that can positively or negatively modulate the biological response of immune cells. Certain mushroom derived-glucans and polysaccharide-bound proteins have been shown to act as immunomodulators or biological response modifiers (BRMs). A variety of therapeutic effects often occur when these mushroom-derived polymers interact with the immune system to upregulate or downregulate specific aspects of the responses of the host. Whether certain compounds enhance or suppress immune responses can depend on a number of factors including dosage, route of administration, timing and frequency of administration, mechanism of action, or the site of activity.
Many mushroom-derived polysaccharides appear to fit the accepted criteria for BRM compounds. They cause no harm and place no additional stress on the body, they assist the body to adapt to the various environmental and psychological stresses, and they have a non-specific action on the body, supporting all the major systems, including nervous, hormonal, and immune systems, as well as regulatory functions.
The anti-tumor polysaccharides isolated from mushrooms (fruit-body, submerged, cultured mycelial biomass or liquid culture broth) are either water-soluble β-D-glucans, β-D-glucans with heterosaccharide chains of xylose, mannose, galactose, or uronic acid or β-D-glucan-protein complexes – proteoglycans.
While the role of medicinal mushrooms in immunomodulation and anti-cancer activities represents the central theme of much of the conducted research, it is pertinent to observe that many of the medicinal mushrooms have been highly valued for other medicinal properties including hypercholesterolemia, high blood pressure, diabetes, anti-viral, anti-bacteria, and antioxidant and free radical scavenging.
Mushroom-Derived β-glucans are Safe
The safety criteria for mushroom-derived β-glucans have been exhaustively carried out in pre-clinical experiments. Acute, subacute, and chronic toxicity tests have been carried out together with administration during pregnancy and lactation with no adverse effects. There were no anaphylactic reactions and no effects in mutagenicity and haemolysis tests, blood coagulation and a wide range of other regulatory tests.
There was no evidence of genotoxicity. Similar results have been obtained with other β-glucans. When applied to humans in Phase 1 clinical tests, the β-glucans demonstrate remarkably few adverse clinical reactions.
Therapeutic Properties of Medicinal Mushrooms
In the 2001 report Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage with Special Emphasis on Cancer Treatments, a wide variety of mushroom polysaccharides, including Lentinan (from L. edodes), Schizophyllan (from S. commune), PSK and PSP (from Trametes versicolor), and Grifron-D (from the Maitake mushroom G. frondosa) and others are described, and their properties are shown to satisfy the criteria for BRMs.
Many of these mushroom-derived polymers potentiate the host’s innate (non-specific) and acquired (specific) immune responses in a similar manner, where they activate many kinds of immune cells that are vitally important for the maintenance of homeostasis. Key innate responses that are stimulated by these mushroom derived-β-glucans or polysaccharide-protein complexes include host T-cells (such as cytotoxic macrophages, monocytes, neutrophils, natural killer cells, and dendritic cells) and chemical messengers (cytokines such as interleukins, interferon and colony stimulating factors) that trigger complement and acute phase responses.
Moreover, mushroom polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and cytokine receptors. In addition, acquired responses are also enlisted, where lymphocytes that govern antibody production (B cells) and cell-mediated cytotoxicity (T-cells) are stimulated. While the immune system is shrouded in tremendous complexity, our current understanding shows that it is regulated in an orchestrated dynamic manner.
Mushroom-derived polysaccharides have shown anti-tumour activities in both pre-clinical models and in clinical trials. Although the mechanism of their anti-tumour action is still not completely clear, Lentinan, Schizophyllan, PSP, PSK and other mushroom polysaccharides appear to mediate their anti-tumour activity by activation or augmentation of the host’s immune system (via stimulated cytotoxic macrophages, cytotoxic T-cells and antibody-mediated cytoxicity of targeted cancer cells), rather than direct cytotoxicity.
Thus, both cell-mediated immune responses against the target T-cells initiated by macrophage-lymphocyte interactions and cytoxicity induced by antibodies to target T-cells are believed to contribute to the elimination of targeted tumour cells. Recent evidence suggests that several mushroom polysaccharides may also possess cytotoxic properties. Grifron-D from G.fondosa mushroom was reported to induce apoptosis (programmed cell death) in human prostate cancer cell-lines.
IMMUNE-ASSIST™ Incorporates Polysaccharide Extracts from Six Organically Grown Medicinal Mushrooms
In China, Japan, Korea, and more recently in the US, hundreds of mushroom species have been studied during the past 20 years. Extracts from most of the medicinal mushrooms show a common property of enhancing immune function by modulating cell-mediated immunity. Simply put, such mushroom extracts seem to turn on cells in the immune system, which appear to have significant disease-fighting properties. In fact, three different anticancer drugs extracted from mushrooms have been approved by the Japanese equivalent of FDA (that is, the Japanese Health and Welfare Ministry). These three are lentinan, derived from shiitake; PSK, derived from coriolus versicolor; and schizophyllan, derived from suehirotake.
Based upon a a large amount of research, a US-based company has formulated Immune-Assist™ , which includes a combination of more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of medicinal mushrooms. These include Agaricus blazei, Cordyceps sinensis hybrid, Lentinula edodes(shiitake), Grifola frondosa (maitake), Ganoderma lucidum (reshi), and Coriolus versicolor.
Immune-Assist™ contains simple polysaccharides similar to many other products on the market, but it also contains much more complex polysaccharides like the cross-linked beta mannans and beta-glucans, as well as hetero-polysaccharides which combine both alpha- and beta-bound monosaccharides into the same molecule. This is the reason that Immune-Assist™ shows such a greater range of immuno-modulation bioactivity than other bran-based supplements. Included among the important substances in Immune-Assist™ are Arabinoxylane, Lentinan, Grifolan (Dr. Nanba’s original Maitake D-Fraction), PSK and PSP, and Active Hemicellulose Correlated Compound (AHCC).
Below we provide a brief summary of the research and clinical studies for each of the mushrooms contained in Immune-Assist™:
Shiitake is now the most popular and most cultivated exotic mushroom in the world. In China, shiitake has a history that dates back to the Ming Dynasty (1368–1644 ACE). The mushroom was used not only as a food but was taken as a remedy for upper respiratory diseases, poor blood circulation, liver trouble, exhaustion and weakness, and to boost chi, or life energy. It was also believed to prevent premature aging. Today the shiitake is recognized for its antitumor action and has been extensively researched in regard to its immunologic activity. The initial antitumor research was performed in 1969 by Tetsuro Ikekawa at Purdue University, along with colleagues at the National Cancer Center Research Institute in Tokyo. The researchers found that water extracts of shiitake produced high rates of tumor inhibition in mice (72–92%). Ikekawa later identified a polysaccharide in shiitake called lentinan as having powerful antitumor activity.
Coriolus (or Trametes) versicolor is the most thoroughly clinically researched mushroom. An extract of Coriolus versicolor known as PSK is sold in Europe and Japan. It is the best-selling cancer drug in the world and recently accounted for more than 25% of Japan’s total national expenditure for anticancer agents. In addition to possessing many different antitumor properties, it is also an immunostimulant; demonstrates anti-viral activity; enhances T-cell proliferation; and has been shown to improve both disease-free and survival rates in cancer patients. In an 8-year clinical test of breast cancer patients, and in another 5-year study, it was shown that the polysaccharide compounds contained within Coriolus versicolor work particularly well as an adjuvant for cancer therapies, exhibiting diverse biological activities.
Maitake may be even more potent than any of the other mushrooms previously studied. This legendary giant mushroom has been studied for its anticancer, anti-diabetic, anti-hypertensive and anti-hyperlipemic effects since the mid-1980s. Its anti-HIV activity in vitro was demonstrated in tests conducted by the Japan Institute of Health and the US National Cancer Institute in early 1992. Among various extracts obtained from the Maitake mushroom, a specific extracted fraction named Maitake D-fraction is the active constituent. This extract contains beta-1, 3-glucans and beta-1, 6-glucans protein-bound polysaccharides. It has demonstrated remarkable antitumor activity by activating the immune system through oral administration.
The Chinese people have long used Cordyceps sinensis to promote overall good health, and modern research indicates that it does indeed support liver, kidney, heart, and immune system function. Cordyceps sinensis has been used to protect the bone marrow and digestive systems of mice from whole body irradiation. One experiment noted that Cordyceps may protect the liver from damage. An experiment with mice indicated the mushroom may have an anti-depressant effect. Researchers have observed that Cordyceps has a hypoglycemic effect and may be beneficial for people with insulin resistance. Cordyceps mushroom extracts have been shown to stimulate the number of T helper cells, prolong the survival of lymphocytes, enhance TNF-alpha and interleukin 1 production, and increase the activity of natural killer cells. One study indicates that cordyceps can stimulate progesterone production in animal cells. Another study has shown that cordyceps may be effective against tumor cells by down-regulating MHC class II antigen expression. In addition, historical use data suggests that cordyceps can cause a reduction of cyclosporin and aminoglycoside-induced renal toxicity.
Reishi possess anti-tumor, immunomodulary, and immunotherapeutic activities, supported by studies on polysaccharides, terpene, and other bioactive compounds isolated from fruiting bodies and mycelia of this fungus. It has also been found to inhibit platelet aggregation, and to lower blood pressure (via inhibition of angiotensin-converting enzyme), cholesterol and blood sugar. Laboratory studies have shown anti-neoplastic effects of fungal extracts or isolated compounds against some types of cancer. In an animal model, Reishi has been reported to prevent cancer metastasis, with potency comparable to Lentinan from shiitake mushrooms. The mechanisms by which Reishi affect cancer may target different stages of cancer development include: 1) inhibition of angiogenesis (formation of new, tumor-induced blood vessels created to supply nutrients to the tumor) mediated by cytokines, 2) cytotoxicity, 3) inhibition of migration of the cancer cells and metastasis, and 4) inducing and enhancing apoptosis of tumor cells. Besides effects on mammalian physiology, Reishiis reported to have anti-bacterial and anti-viral activities. Reishi is reported to exhibit direct anti-viral effects with the following viruses: HSV-1, HSV-2, and influenza.
Agaricus blazei is an edible mushroom native to Brazil and cultivated in Japan and the USA for its medicinal uses. It has been used to treat arteriosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis, and cancer. In vitro experiments and studies done in mice have shown that Agaricus has immunomodulatory, antitumor, and antimutagenic properties. The polysaccharides and anti-angiogenic compounds present in Agaricus are thought to be responsible for its antitumor properties. Such effects are believed to be exerted by immunopotentiation or direct inhibition of angiogenesis. A recent randomized study showed that oral administration of Agaricus extract improved the natural killer cell activity and quality of life in gynecological cancer patients undergoing chemotherapy. Agaricus was also shown to have antidiabetic effects in vitro and in animal studies. In addition, results from a study done in human subjects with type 2 diabetes suggest benefits of Agaricus extract in improving insulin resistance, and a pilot study indicates that Agaricus extract may reduce weight, BMI, body fat, and serum glucose and cholesterol levels in healthy individuals.
AHCC as a Component of Immune-Assist™ Daily Formula
AHCC is produced by from the enzymatic action of vegetable sources with mycelial extracts from several different mushrooms. There is about four times more AHCC in each dose of Immune-Assist™ than there is in other AHCC products on the market.
AHCC is a food substance that contains a broad range of polysaccharides. It is believed that a special polysaccharide with a molecular weight of about 5,000 and an alpha 1,4 glucan linkage in this mushroom extract is primarily responsible for the powerful immune enhancing effects on natural killer cells. A heavier polysaccharide in the extract appears to have a powerful stimulating effect on macrophages which, in turn, further stimulates the immune system including a number of cytokines (Interleukin-2, Interleukin-12, Tumor Necrosis Factor [TNF], and Interferon). Furthermore, some research has indicated that components of AHCC may have direct cytotoxic effects on cancer cells and prevent metastases from occurring.
Natural Killer Cells
The human immune system is comprised of more than 130 subsets of white blood cells. Natural Killer (NK) cells make up roughly 15% of all human white blood cells. They provide the first line of defense for dealing with any form of invasion to the body. Each NK cell contains several small granules that act as chemical destroyers. Once an NK cell has recognized a cancer cell, for example, it attaches itself to the cell’s outer membrane and injects these granules directly into the interior of the cell. The granules then destroy the cancer cell within five minutes. The undamaged NK cell then moves on to other cancer cells and repeats the process. When the immune system is particularly strong, active NK cells will often take on more than one cancer cells or other infected cells at the same time.
NK Cell Activity, Not Number, Determines Immune System Strength
Unlike other white blood cells, inadequate numbers of NK cells are very rarely a problem. Instead, it is the activity of the cells that generally determines whether one is sick or healthy. As long as the NK cells are active, everything remains under control. If NK cells lose their ability to either recognize or destroy the invader, however, the situation can deteriorate rapidly. In AIDS and cancer patients, NK cell activity is probably the primary criteria for estimating the chances of survival. It’s commonly accepted that when NK cells cease to function, the end is near.
In addition, research has now confirmed that individuals with low NK cell activity are significantly more susceptible to autoimmune diseases, chronic fatigue syndrome, viral infections and the development of cancerous tumors.
Doctors can test NK cell activity with a test called the NK cell function test. Basically, a blood sample is taken from the patient and placed in a vial containing live tumor cells. After four hours, a count is taken to determine what percentage of the cancer cells have been destroyed by the NK cells. The higher the percentage, the more active the cells. This test is referred to as the 4 hour Chromium-release assay. Your doctor can order the test from Immune Sciences Lab in Beverly Hills, CA at 310-657-1077.
How IMMUNE-ASSIST™ Increases NK Cell Activity and Immunity
The capacity of Immune-Assist™ to boost NK activity and overall immunity appears to stem from the following:
1) Immune-Assist™ increases the number of explosive granules in NK cells. The more granules an NK cell carries, the more cancer and virus-infected cells it can destroy,
2) Oral ingestion of Immune-Assist™ can increase NK activity as much as 300% (or even higher),
3) It increases interferon (IFN) levels. Interferon is another potent compound produced by the body that both inhibits the replication of viruses and other parasites and increases NK cell activity,
4) Immune-Assist™ increases the formation of Tumor Necrosis Factors (TNFs). TNFs are a group of proteins that help destroy cancer cells,
5) It increases number and the activity of other lymphocytes, especially T-cells (up to 200%) and macrophages,
6) It stimulates cytokine (IL-2, IL-12, TNF, and IFN) production, which stimulates immune function.
Applications for Immune-Assist™
Applications for Immune Assist™ include: 1) recurrent infections, such as colds, flu, and parasites, 2) gum disease, 3) heart disease, 4) peptic ulcer, 5) cancers, 6) slow healing wounds, 7) digestive problems, 8) AIDS, 9) hepatitis, 10) multiple sclerosis, and 11) autoimmune illnesses. Immune Assist™ has not exhibited side effects and is completely non-toxic even after years of use at therapeutic levels.
Owing to its tremendous immune enhancing effects, Immune-Assist™ is likely to be of significant benefit to individuals suffering from a wide range of conditions. Impaired immunity is a result of a wide range of poor lifestyle habits including high stress levels, exposure to high levels of toxins, and poor nutritional status. As such individuals in the following categories could also benefit from Immune Assist™:
- Individuals who constantly work with paint (artists, house painters, etc)
- Chemical and refinery workers and others exposed to heavy doses of toxic chemicals
- Heavy smokers
- Heavy drinkers
- Individuals with gum disease
- Individuals with peptic ulcers
- Individuals with prostate infections
- Individuals with chronic fatigue syndrome
- Individuals with diabetes
- Individuals with heart disease
- Individuals experiencing autoimmune deficiencies (multiple sclerosis, lupus, rheumatoid arthritis)
- Individuals with recurrent infections, such as colds, flu, yeast, and parasites
- Individuals whose families exhibit a significant history of cancer
- Individuals with slow healing wounds
The dosages used in studies are scientifically based on repeated NK cell activity tests. As such, they are consistent and easy to follow. They fall into two types:
1) For cancer, HIV or other life-threatening condition, take three grams per day for two-to-four weeks, then one gram per day until the problem is resolved. Some people continue to take the maintenance dosage even after the problem has been resolved, while others stop taking it and resume if the problem returns. In rare cases taking as much as six grams daily was necessary.
2) As a form of prevention take one gram per day.
In all of the studies, it has been found that taking 3 grams a day resulted in a dramatic increase in NK cell activity within one to two weeks. At the lower dosage of only one gram per day, the same activity wasn’t reached until about four weeks. Thus, the initial heavy doses of three grams per day. Even after the dosage is dropped back to one gram per day, NK cell activity will continue to increase. It is best to take the Immune-Assist™ capsules with meals in divided doses. For example, when taking three grams per day (which works out to six 500 mg capsules), two capsules can be taken with each meal. When you reduce the dosage down to one gram a day (two capsules), you can take one capsule at breakfast and one at dinner.
The importance of a strong, adaptable immune system cannot be underestimated, especially in the context of building (or rebuilding) health and for successful rejuvenation. While there are other useful immune building supplements (e.g., echinacea, garlic, olive leaf extract), Immune Assist™ is highly effective for boosting immunity as part of a complete program for rejuvenation.
Learn more about Immune-Assist™ on the HPDI website.
1) Healing Mushrooms by Dr. Georges Halpern, MD, PhD., 2007, http://www.alohamedicinals.com/HealingMush_Private_10-18-06.pdf
2) Medicinal Mushrooms: their Therapeutic Properties and Current Medical Usage with Special Emphasis on Cancer Treatments. 2001
Authors: JOHN E SMITH BSc MSc PhD DSc FIBiol FRSE Emeritus Professor of Applied Microbiology, University of Strathclyde Chief Scientific Officer, MycoBiotech Ltd, Singapore. NEIL J ROWAN BSc MSc PhD MIBiol MIFST Lecturer, Department of Bioscience, University of Strathclyde, RICHARD SULLIVAN BSc MD PhD Head of Clinical Programmes, Cancer Research UK.
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3) Anti-Cancer Properties: A peer-reviewed article by Dr. Solomon Wasser of University of Haifa, Israel : Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides