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AMAZING IMMUNE-ASSIST™ MUSHROOM FORMULA

Dr. Hank Liers, PhD Immune-Assist™ medicinal mushroom extracts

HPDI’s amazing IMMUNE-ASSIST™ mushroom formula is a combination of more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of organically grown medicinal mushrooms. These include Agaricus blazei, Cordyceps hybrid (sinensis and militaris), Lentinula edodes (shiitake)Grifola frondosa (maitake)Ganoderma lucidum (Reishi), and Coriolus versicolor.

IMMUNE-ASSIST™ Daily Formula 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 into the same molecule. This is why 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).

Many mushroom-derived polysaccharides appear to fit the accepted criteria for immunomodulators or biological response modifiers (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.

MEDICINAL MUSHROOM EXTRACTS: ONE OF THE MOST POWERFUL IMMUNE MODULATORS KNOWN

Recent scientific research has shown that medicinal mushrooms grown on vegetable sources (such as millet, rice bran, buckwheat, milo, etc.) enzymatically activate a process whereby complex cross-linked polysaccharides from the vegetable sources are converted to biologically active immunomodulators. 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 modulate positively or negatively the biological response of immune cells. Certain mushroom derived-glucans and polysaccharide-bound proteins have been shown to act as immunomodulators, where these polymers interact with the immune system to upregulate or downregulate specific aspects of the responses of the host and this may result in various therapeutic effects.

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.

The most effective 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 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 cholesterols control, blood pressure support, blood sugar support, assistance with viral and bacterial balance, and antioxidant and free radical scavenging.

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.

In the 2001 report Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage, 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 biological response modifiers. 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 therapeutic activities in both pre-clinical models and in clinical trials. Although the mechanism of their action is still not completely clear, Lentinan, Schizophyllan, PSP, PSK and other mushroom polysaccharides appear to mediate their activity by activation or augmentation of the host’s immune system (via stimulated cytotoxic macrophages, cytotoxic T-cells and antibody-mediated cytoxicity of targeted 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 abnormal 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 cell-lines.

IMMUNE-ASSIST™ DAILY FORMULA INCORPORATES POLYSACCHARIDE EXTRACTS FROM SIX MEDICINAL MUSHROOMS

In China, Japan, Korea, and more recently in the USA, hundreds of mushroom species have been studied during the past 30 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 healing properties. In fact, three different 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 on the latest research a USA-based company (Aloha Medicinals, Inc.) has formulated for Health Products Distributors, Inc. IMMUNE-ASSIST™ Daily Formula. This formula contains 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 hybrid (sinensis and militaris), Lentinula edodes (shiitake)Grifola frondosa (maitake)Ganoderma lucidum (Reishi), and Coriolus versicolor.

Immune-Assist™ Medicinal Mushrooms

RESEARCH RELATED TO 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.

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 an immunostimulant; demonstrates anti-viral activity; enhances T-cell proliferation; and has been shown to improve both disease-free and survival rates in patients.

Maitake may be even more potent than any of the other mushrooms previously studied. This legendary giant mushroom has been studied for its anti neoplastic, 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 cell-protective activity by activating the immune system through oral administration.

The Chinese have long used Cordyceps sinensis and militaris to promote overall good health, and modern research indicates that it does indeed support liver, kidney, heart, and immune system function. Cordyceps 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. 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.

Reishi possess 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.

In an animal model, Reishi has been reported to prevent metastasis, with potency comparable to Lentinan from shiitake mushrooms. The mechanisms by which Reishi may target different stages of abnormal growth development include: 1) inhibition of angiogenesis (formation of new blood vessels created to supply nutrients to the abnormal cell) mediated by cytokines, 2) cytotoxicity, 3) inhibition of migration of the cells and 4) inducing and enhancing apoptosis. 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 neoplasms. In vitro experiments and studies done in mice have shown that Agaricus has immunomodulatory and antimutagenic properties. The polysaccharides and anti-angiogenic compounds present in Agaricus are thought to be responsible for its therapeutic properties. Such effects are believed to be exerted by immunopotentiation or direct inhibition of angiogenesis.

ACTIVE HEMICELLULOSE CORRELATED COMPOUND (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, TNF, and Interferon). Furthermore, some research has indicated that components of AHCC may have direct cytotoxic effects on unhealthy cells.

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 an unwanted 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 cell within five minutes. The undamaged NK cell then moves on to other cells and repeats the process. When the immune system is particularly strong, active NK cells will often take on more than one cell or other infected cells at the same time.

NK CELL ACTIVITY, NOT NUMBER, DETERMINES THE STRENGTH OF THE IMMUNE SYSTEM

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 many patients with serious health conditions, NK cell activity is probably the primary criteria for estimating the chances of survival. It is 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 abnormal growths.

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 appropriate live cells. After four hours, a count is taken to determine what percentage of the cells have been destroyed by the NK cells. The higher the percentage, the more active the cells. This test is referred to as the four 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™ DAILY FORMULA 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) It increases the number of explosive granules in NK cells. The more granules an NK cell carries, the more unhealthy cells it can destroy.

2) Oral ingestion 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) It increases the formation of TNFs. TNFs are a group of proteins that help destroy unwanted 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.

SUPPLEMENT FACTS

COMPOSITION: Two vegetarian capsules provide the following percentage of the Daily Value:

NUTRIENT AMOUNT % Daily Value
Proprietary Beta-Glucan complex plus nucleosides and other bioactive compounds extracted from six well-known, organically grown medicinal mushrooms: Agaricus blazei, Cordyceps sinensis and Cordyceps militaris, Lentinula edodes, Grifola frondosa, Ganoderma lucidum, and Coriolus versicolor. 1,000 mg *

* No established Daily Value

USAGE

DIRECTIONS: As a dietary supplement take two capsules per day in divided doses, or as recommended by a health care professional. In severe conditions, we suggest six (6) capsules per day for two weeks to build up immune activity, then maintaining a dosage of two (2) capsules per day. Alternatively, Immune-Assist™ can be taken at the time of exposure or first signs of illness, in which case we recommend taking two caps three times per day.

INGREDIENTS: IMMUNE-ASSIST™ contains a proprietary organic grown blend grown on organic white milo (growing substrate) and veggie capsule.

IMMUNE-ASSIST™ does not contain: wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, GMOs, sugar, wax, preservatives, colorings, or artificial flavorings.

REFERENCES

1) Healing Mushrooms by Dr. Georges Halpern, MD, PhD, 2007.

2) Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage with Special Emphasis on Cancer Treatments. Smith, Rowan and Sullivan, 2001.

3) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides (PDF 269 kb). A peer-reviewed article by Dr. Solomon Wasser of University of Haifa, Israel, 2002.