APPLICATION OF M2 MUSHROOM MATRIX FORMULA TO HUMANS WITH CHRONIC IMMUNODEFICIENCY DISEASES
Author: Marvin S. Hausman MD; Okezie I Aruoma PhD DSc
Date: February 1, 2007
"Confidential and Proprietary: These materials may not be used, reproduced or disseminated without the prior written consent of the authors"
The natural organic mushroom formula, named M2 ™, is a special blend of mushrooms, and represents an innovative new approach to human nutritional supplementation. The coupling of mushroom enzymatic activity with bioactive antioxidant/anti-inflammatory substances results in a unique natural organic product with the potential to prevent and alleviate conditions associated with oxidative stress and chronic inflammatory changes. These conditions include but are not limited to - Viral infections including HIV/Chronic Immunodeficiency Diseases, cardiovasculat disease, stroke, Alzheimer's disease, gastrointestinal disorders.
For centuries, mushrooms have been consumed for their medicinal benefits and have been recognized for their powerful functional aspects in addition to their flavors and textures. Long used as a mainstay in traditional Asian medicine, efforts to introduce these products into Western diets is accelerating. Golden Gourmet Mushrooms of San Marcos, California, a pioneer in specialty mushroom cultivation in the USA, and Northwest Medical Research Partners of Stevenson, Washington, a medical/scientific research organization (GGM/NW), have joined forces to introduce specialized mushroom based bioactive formulas designed to provide the health stimulative effects of these foods to humans as well as to the animal world.
- FOCUS:
Use a unique combination of bioactive mushrooms to address the particular nutritional and medicinal needs of humans with chronic immunodeficiency diseases.
- Mushrooms contain:
(1) some of the most powerful anti-oxidative properties known in any food product, (2) strong anti-viral properties, (3) excellent anti-inflammatory active ingredients, and (4) proven anti-tumoral elements.
GGM/NW through its unique proprietary mushroom matrix formula seeks to provide an organic complex matrix of bioactive substances that address the nutritional and physiologic needs and requirements of people in a uniquely efficient and effective manner.
Many human nutritional supplements contain synthetic chemicals and nutrients whose absorption, cell penetration, and physiologic effect are questionable. The M2™ Mushroom Matrix is a unique mushroom blend which contains a natural enzyme backup to assist a person in proper absorption and utilization of needed nutrients.
Mushrooms have evolved by means of externally digesting foods by secreting enzymes and acids into their immediate environs and then absorbing nutrients using netlike chains. The Mushroom Matrix concept is to use various types of edible whole mushrooms in a unique blend that optimizes each mushroom's enzymatic activity during the initial phases of growth. The mushrooms in our blend essentially work for us through the concept of enzymatic digestion of designed starter substrates. This technology was developed in a cooperative research venture with Dr. Robert Beelman, Professor of Food Science at Pennsylvania State University. This production approach results in high levels of polyphenols, beta-glucans, L-Ergothioneine, selenomethionine and other unique bioactive components.
The secret lies in the use of a complex mushroom matrix containing active enzymatic bioactive materials. This nutritional supplement is presented to a person in a form that is easily absorbable, bioavailable and active.
Antioxidants:
All living organisms are exposed on a daily basis to attacks by free radicals, also called reactive oxygen species and to survive require a powerful antioxidant defense system. Antioxidants are the body's defense system and are involved in the prevention of cellular damage, a common pathway for infections- bacterial and/or viral, aging, cancer, and many other diseases. Examples of micronutrient (vitamin) antioxidants include, vitamin E, beta-carotene, and vitamin C. L-Ergothioneine (ERGO), a substance mushrooms have in abundance, is also one of the most potent antioxidants in the world.
Free radicals:
Free radicals are formed from molecules by breaking a bond such that each fragment keeps one electron. Free radicals may also be formed by collision of the non radical species by a reaction between a radical and a molecule -which must then result in a radical since the total number of electrons are odd, by cleavage of a radical to give another radical and, by oxidation or reduction reactions. Aerobic organisms, including man, animals, and plants, are constantly challenged by reactive nitrogen species (RNS) and reactive oxygen species (ROS). These are either synthesized endogenously, e.g. in energy metabolism and by the immune defence system of the body, or produced as reactions to exogenous exposures such as cigarette smoking, imbalanced diet, exhaustive exercise, environmental pollutants and food contaminants. Inflammation, cellular and redox signalling mechanisms are now widely recognized to play major roles in the pathophysiology of numerous chronic and acute disease states including HIV/AIDS. This implication of oxidative and nitrosative stress in the etiology and progression of several acute and chronic clinical disorders has led to the suggestion that antioxidants can have health benefits as prophylactic agents. Epidemiological studies have consistently shown an inverse association between consumption of vegetables and fruits and the risk of cardiovascular diseases and certain forms of cancer. Although the protective effects have been primarily attributed to the well-known antioxidants, such as Vitamin C, Vitamin E and beta-carotene and plant phenolics, we now put forward the potent bioactive substance L-Ergothioneine as a beneficial dietary antioxidant.
L-Ergothioneine (LE), a substance mushrooms have in abundance, is one of the most potent antioxidants in the world.
Humans cannot manufacture LE.
- LE is taken up from the soil by various plants and is then consumed in the diet by
humans (Audley BG and Tan CH. 1968. The uptake of ergothioneine from the
soil into the latex of Hevea Brasiliensis. Phytochemistry 7:1999-2000.)
- 1 unit of LE approximately equals 7, 000 units of Trolox (water soluble vitamin
E). (Bank G and Schauss A. 2004. Antioxidant testing: an ORAC update.
Nutraceuticals World 3:68-71
- What is most fascinating is that mammals cannot synthesize LE but contain a
specific transport system to ensure delivery of this essential nutrient to key cells
within the body (Grundemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels
R, Jung N, Rubbert A, Schomig E. 2005. Discovery of the ergothioneine
transporter. Proceedings of the National Academy of Science 102(14):5256-5261
- No other needed nutrient in the body has its own transport system!
- The M2 ™ mushroom formula has been designed to provide high levels of ERGO
that specifically fit into this transporter to ensure delivery of this required
antioxidant/essential nutrient to the "cellular power plants" called mitochondria
- Most important in the HIV/AIDS context, LE has shown an important anti-viral
role by its ability to inhibit cell death induced by hydrogen peroxide and to inhibit
DNA oxidation by peroxynitrite [Aruoma O I, Whiteman M, England T G and
Halliwell B (1997). Antioxidant action of ergothioneine: Assessment of its ability
to scavenge peroxynitrite. Biochemical and Biophysical Research
Communications 231: 389-391], [Aruoma O I, Spencer J P E and Mahmood N
(1999). Protection against oxidative damage and cell death by the natural
antioxidant ergothioneine. Food and Chemical Toxicology 37: 1043-1053.]
Viral Pathogenesis and Mutation:
Role of Free Radicals:
Oxygen radicals and nitric oxide (NO) are generated in excess in bacterial and viral infections.
These reactive oxygen species cause oxidative tissue injury and mutagenesis through oxidation and nitration of various biomolecules. Moreover, the unique biological properties of free radicals can accelerate viral mutation while also decreasing a host's immune response.
NO induced immunosuppression contributes to the pathogenesis of virus infections.
Role of Heavy Metals:
The National Cancer Institute has reported that diets deficient in selenium may
increase mercury toxicity and also impair immunologic function ( Ferencik M,
Erbringer L. Modulatory effects of selenium and zinc on the immune system. Folia
Microbiol (Praha). 48(3): 417-426)
Role of the Immune System:
Compromised immune systems increase susceptibility to bacterial and viral infections like HIV
In many regions of the world, such as Africa and India, immune systems are compromised and HIV spread is exacerbated by poor nutrition, bad sanitation and impure water.
HIV/AIDS Dementia and the potential prophylactic potentials of antioxidants
HIV is known propensity to infect the CNS and cause neurological disease but the associated HIV neurocognitive disorders remain to be fully understood. The advent of combination antiretroviral therapy has improved the health of millions of those living with HIV, the penetration into the CNS of many such therapies is limited, and patients' quality of life continues to be diminished by milder, residual neurocognitive impairment. Given that synaptodendritic neuronal injury is emerging as an important mediator of such deficits in HIV it is increasingly argued that carefully selecting specific anti-retrovirals and supplementing them with neuroprotective agents, physicians might be able to facilitate innate CNS repair, promoting enhanced synaptodendritic plasticity, neural function and clinical neurological status. [Ellis R, Langford D and Eliezer Masliah E (2007). HIV and antiretroviral therapy in the brain: neuronal injury and repair Neuroscience Reviews: 8 33-44].
Although HAART has had considerable success in combating HIV-related immune collapse and has prevented many of the former end-stage complications of AIDS. However, with increased survival times the prevalence of minor HIV-associated cognitive impairment appears to be rising among treated patients and this may be a particular risk for older individuals. HIV encephalitis (HIVE) is still prevalent in treated patients although attenuated forms of HIVE and CNS opportunistic disorders are also observed. Some subjects show very significant CNS lymphocytic infiltrates in the context of HAART-induced immune reconstitution. HIV-associated cognitive impairment correlates best with the increased presence of activated, though not necessarily infected, microglia and CNS macrophages.
[Bell J E (2004). An update on the neuropathology of HIV in the HAART era. Histopathology. 45: 549-559.].
Evidence of Antiviral Activities of Mushrooms:
Mycelial extracts of shiitake mushrooms grown on sugarcane and rice bran contain an anti-viral water-soluble lignin.
A polysaccharide from turkey tail (Trametes versicolor) mushrooms inhibits HIV type 1 infection.
A novel ubiquitin-like glycoprotein from oyster mushrooms (Pleurotus ostreatus) inhibited HIV.
The National Institutes of Health (NIH) has funded a clinical study in patients with HIV using oyster mushrooms in combination with protease inhibitors .
Role of the GGM/NW Mushroom Formula in combating AIDS:
This combination of mushrooms with specific contained bioactive agents offers protection against HIV/AIDS in several ways:
(1)Through direct antimicrobial action.
(2)Increasing a person's natural defense/immune system.
(3)Contained within the mushroom formula is a combination of beta-glucans, polyphenols, enzymes, acids, L-Ergothioneine, and selenomethionine; these bioactive agents, alone and in concert, can control infections.
(4)Natural mushroom selenomethionine has the potential to strengthen the cell membrane against viral penetration.
(5)L-Ergothioneine is an extremely potent anti-oxidant and has been shown to inhibit HIV transcription. Gene expression in retroviruses such as HIV-1 is regulated at multiple levels. Transcriptional regulation takes place predominantly via the interactions of cellular RNA polymerases, TATA binding protein, and transcription factors such as NF-?B, that bind to specific target DNA sequences in the viral "long terminal repeat" (LTR), which serves as the promoter-enhancer for the viral genome when integrated in host DNA. A novel viral gene product, pro-fs, as the transcriptional activator, a variant of the standard HIV-1 LTR reporter gene assay was used to investigate its potential for assessing the inhibitory effects of antioxidants and phytochemicals on HIV-1 transcription. The diet- derived antioxidant ergothioneine showed consistent inhibitory activity on the HIV-1 LTR assessed using either TNF-a or pro-fs as the activator (Pro-fs contains a well conserved peptide sequence with local similarity to the DNA binding loop of NF-?B, which is also the target site of thioredoxin binding to NF-?B) [Xiao L, Zhaoa L, Lia T, Diane K. Hartlea D K, Aruoma OI and Taylor E W (2006). Activity of the dietary antioxidant ergothioneine in a virus gene-based assay for inhibitors of HIV transcription. BioFactors 27 (2006) 157-165 157]
(6)Although HAART has had considerable success in combating HIV-related immune collapse and has prevented many of the former end-stage complications of AIDS, HIV-positive individuals are still developing HIV-dementia. This condition can be challenging to diagnose and can have a major impact on the patient's quality of life, affecting their cognition, behavior, and motor performance. GGM/NW Mushroom Formula has the potential of being an effective prophylactic agent in combating the development of AIDS.
(7)Not everyone can afford AIDS drugs Research is needed to look at food plants and medicinal plants for help in nutritional management of HIV/AIDS disease and AIDS -related dementia (a consequence of the same). Intervention strategies involving phytoceuticals and/or nutraceuticals with a defined scientific handle can be envisaged hence the interest in the novel functional mushroom formula enriched with L-Ergothoneine.
In summary, the GGM/NW mushroom formula represents an innovative new approach to control of viral penetration and spread through nutritional supplementation. The coupling of enzymatic activity with bioactive antioxidant/anti-inflammatory substances results in a unique product with the potential to prevent and alleviate conditions associated with oxidative stress and chronic inflammatory changes. The enzymatic activity of each mushroom in the formula is matched to specific growth substrates to produce increases in the amounts of key bioactive substances, such as L-Ergothioneine and selenomethionine. This unique blend of mushrooms with a complete array of bioactive antioxidant/anti-inflammatory agents contains in one package a nutritional supplement that can be used in the battle against HIV/AIDS.
Definitions:
Antioxidant:
Antioxidants are chemicals that reduce the rate of particular oxidation reactions and are important in the context of biology. All living organisms maintain a reducing environment inside their cells and these cells have to maintain a system of antioxidants to prevent chemical damage to the cells' components by oxidation. Antioxidants are widely used as ingredients in dietary supplements used for health purposes.
Oxidation:
The increase in oxidation state of an atom is known as oxidation; a decrease in oxidation state is known as reduction. These reactions involve the transfer of electrons. A net gain in electrons is reduction and a net loss in electrons is oxidation
Polyphenols:
Group of chemical substances such as tannins, lignins and flavonoids. Research indicates that polyphenols have antioxidant properties with potential health benefits. Biological effects include protection against cardiovascular diseases, stimulation of blood flow and increased insulin sensitivity
Beta-glucans:
Glucans are polysaccharides made up of chains of glucose molecules. These carbohydrates have the potential to prevent and treat cancer, lower cholesterol, treat viral diseases and diabetes, and increase immune system function.
L-Ergothioneine:
sulfur containing intracellular antioxidant that cannot be synthesized by animal species and is only available form dietary sources, such as mushrooms. Extremely potent antioxidant that scavenges reactive oxygen species and stimulates red blood cell energy production.
Selenomethionine:
amino acid containing selenium that cannot be synthesized by higher animals but can be obtained from plant material as well as mushrooms. Research has shown protective effects of selenium in humans against aging, heart disease, arthritis, as well as Alzheimer's disease.
Amino Acids:
Basic components of proteins and are "the building blocks" of the body. Amino acids help build cells, repair tissue and form antibodies to fight bacteria and viruses, carry oxygen throughout the body and participate in muscle activity.
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