MYCOTOXINS & THEIR EFFECT ON THE HUMAN BODY - Part 1

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MYCOTOXINS AND THEIR EFFECT ON THE HUMAN BODY

Presented to

World Safety Organization
17th International Environmental Safety & Health Conference& Exposition
November 3 - 5, 2003

Conference Theme: "Safety & Health In the Changing Environment."

ABSTRACT

A mycotoxin is a highly toxic principle produced by molds or fungi. One type, the aflatoxins, is a member of the tricothecene group produced by the fusarium fungus. This has been identified in samples of the so-called "yellow rain" in Southeast Asia, where it is said to have been the cause of many deaths among war refugees. Its presence there is subject to some conjecture, since the Fusarium fungus cannot germinate in the humid environment of that area. There is substantial evidence (blood tests, autopsies, and contaminated gas masks) that the former U.S.S.R. have used such lethal agents in Afghanistan, just as many other countries have used these lethal agents throughout the dawn of history. The human body once exposed to a mycotoxin runs a triple risk to its toxic effects. The triple risk factors are direct toxic effect of the mycotoxin, acquisition of mutated RNAi from the mycotoxin's parent fungus and creation of an internal biofilm, which will harbor a toxic soup of disease.

INTRODUCTION

Mycotoxins represent an important class of xenobiotics (in terms of morbidity), which cause renal injury in humans and food animals.¹ They are not the indigenous microorganisms of man. The flora and fauna indigenous to man are often referred to simply as normal flora. In this context, "flora" denotes all microscopic life forms and "normal" becomes a statistical term. One must not equate normal with nonpathogenic, for many organisms found on and in the body can pose problems under conditions such as the following:

1. Deterioration of the host's defense mechanisms.
2. Relocation of microorganisms, when an organism finds its way to another area of the body previously uninhabited by it.
3. A disturbance of the "normal flora."

Normal floras are commonly referred to as amphibionts, ranging from commensals to pathogens. The amphibionts are obligately parasitic on man and other animals but are not obligately pathogenic. They are encountered at least as often in the absence of disease as in its presence. The indigenous microorganisms may flourish in the general region of tissue damage and contribute to the disease state as opportunists, rather than primary etiological agents. Thus, these organisms may be implicated although Koch's postulates would not necessarily hold true.²

Amphibiont Sites

As a rule, few or no microorganisms are found in the following anatomical locations: blood, larynx, trachea, nasal sinuses, bronchi, esophagus, stomach, upper intestinal tract, upper urinary tract (including the posterior urethra), and posterior genital tract (passage above cervix included). However, in studies with animals, notably dogs and rabbits, microorganisms from the mouth and throat regions and from the lower intestine were found in the blood and other tissues after these animals were subjected to various types of physical or mental stress and trauma. In particular, Clostridium perfringes (one of the causative agents of gas gangrene) has been isolated from the "healthy" tissues of these animals.

The regions of the body that constitute the major habitats for indigenous microorganisms include the skin and contiguous mucous membranes, conjunctivae, upper respiratory tract (oral-pharynx included), mouth, lower intestine, external genitalia, anterior urethra, and vagina. It will become apparent that each habitat has certain characteristics, which allow a different overall range of microorganisms to thrive. These differences can be categorized into the following three types of environment:

1. Extremely high levels of both moisture and nutrients, as in the lower intestines and the mouth.
2. A high level of moisture and a low level of nutrients, as with mucous membranes.
3. A low level of moisture and a moderate level of nutrients, as on the skin.

Other variables include availability of oxygen, pH, temperature, and relative exposures to contaminants and ventilation.

Numbers of total aerobic and anaerobic bacteria in certain anatomical regions:

Lower intestine - approximately 100 billion microorganisms per gram of fecal matter.

Mouth - approximately 1 billion microorganisms per ml of saliva.

Nose - approximately 20,000 microorganisms per ml of nasal washing.

Skin - approximately 1 million microorganisms per cm²; this value is dependent upon the skin surface tested.

Development of the indigenous flora begins with the normal birth process, since the infant has been bathed during the ingestion period in a sterile amniotic fluid. As the baby passes through the birth canal it begins to pick up organisms, many of which may remain with it for its lifetime. Additional microorganisms are acquired by the infant as a consequence of coming into contact with the air of the environment and with hospital personnel. Such organisms may be transient in nature, or may become permanent members of the flora.

Appreciable numbers of bacteria have been cultured from the mouths of infants within 6 to 10 hours of birth and in the feces within 10 to 20 hours.

The human body has various anatomical organ areas, each anatomical area varies in relation to pH, oxygen content, nutrients, and moisture as well as bactericidal factors, thus different organisms will predominate. While the amphibionts persist in their respective locations, saprophytic as well as many parasitic microorganisms are destroyed or excreted. These locations can change as a consequence of changes brought about by the maturation process of the individual, e.g., hormonal regulation, alteration in dietary habits, chemical exposure, IAQ buildings, AIDS and chemotherapy.

The indigenous fungi are primarily saprophytes of soil, which show preference for a parasitic habitat. Because of their primary saprophytic role, it may appear questionable to call them amphibionts. However, according to Rosenbury, an amphibiont may be considered to be any organism, which is ". . . encountered in one or more typical indigenous locations frequently, and distinctly more frequently, than in the adjacent environment." On this basis, and according to the propositions that an organism routinely isolated from the body in the absence of disease may be indigenous, fungi are included, even though they rarely are indigenous to the human body.^{2, 3}

WHAT ARE FUNGI?

Fungi are single cell living forms of life, which inhabit the land, air, and waters of our planet, earth. They are everywhere in our environment, soil and home.

They are more highly developed than bacteria and viruses. They are composed of many more species than are found in other microorganisms. It is estimated that there are over 500,000 different species.

Fungi have been on earth several billion years and, quite remarkably, have had little genetic change over that period of time. They are survivalists. They can change their form from rapidly growing to no growth for thousands of years, such as seen in their living spores which have been found in Egyptian tombs. They secrete and make a poisonous toxin called a mycotoxin.

Single fungi cells can only be seen under the microscope but a colony of these cells makes a visible presence in the form of mushrooms, toadstools and molds on food and other habitats.

While plants, animals and humans are alive and well, the fungi around us are unable to overcome the natural defense mechanisms which higher forms of life possess. But once death overtakes the living, the fungi are the principle undertakers and managers: they reduce all that have ever lived into the molecules from which they were assembled. Biologists call this the carbon cycle while theologist call it "from dust to dust."^{4, 5}

However, there is one exception to this simple balanced equation of life and death and that is that the fungi can attack the living while they are alive.

At its most simplistic perspective, one has many fungi entering the intestinal tract, the nose and lungs, and organs exposed to the world at large. We generally do not develop an infection from these intruders. However, a person might contract a fungal infection such as "athlete's foot" or a "ring worm" on the skin.

At the opposite extreme is the patient with AIDS who faces death-threatening major fungal infections because that person's immune system has lost its effectiveness against fungi. In between the extremes are fungal infections associated with diseases such as diabetes, cancer and other conditions including cross infections amongst humans.

Forturnately, the average person does not succumb to a serious fungal infection such as Candida albicans (yeast) and average life into the 70's.

All humans are colonized by Candida albicans and normal healthy persons do not die from this organism. This organism plays a very little role in causing human diseases. It has been known to have tremendous elevated growth patterns in individuals who have been diagnosed as being multichemical sensitive or acutely poisoned from exposure to hazardous materials, such as urethane, carbamates, nitrogen mustards and other compounds. It is interesting to note that these same chemicals are known to be extrinsic mutagenic agents in both fungi and human genes.6 This type of extrinsic mutagenic activity by chemicals is also known as a "directed mutation."⁷ (See Table 1-1.)

Mycotoxins may be friends or foe. There are as many as 1,000 compounds, classifiable as mycotoxins, where studied by the pharmaceutical industry as potential antibiotics in the 1930's and 1940's only to be discarded as being too toxic for higher life forms to be of value in treating bacterial diseases in humans. Little, if any of the discarded data was published. Yet, what these toxicity studies actually documented was the existence of a large number of fungal-derived toxins, which caused serious, target organ injury in various animal models.

Obviously, in retrospect, what was being seen was the pathology produced by the mycotoxins, in order to understand this toxicity, one only has to look at what some of these mycotoxins, used as medications, causes in humans:

The mycotoxin cyclosporin used for transplantation causes cancer and atherosclerosis, complete with hyperlipidemia in ALL humans who have received it. Many others develop gout and other diseases.

As a friend, the study of such fungal metabolites gave us penicillin at the beginning, which was replaced by a chemical cyanamide man made compound from 1945 to present day. Quite later on cyclosporin, the most potent immuno-suppressant transplantation drug, lovastatin, and the other "statins", which have revolutionized the treatment of hyperlipidemia and atherosclerosis. The latter group is quite interesting in that they were initially developed as anti-fungal agents which just happened to have an effect in lowering blood levels of low density lipoproteins (commonly refereed to as "bad cholesterol").

The members of this group of drugs are joined by another anti-fungal antibiotic, griseofulvin, which is also a remarkably efficient anti-atherosclerosis drug. All of this goes a long way to confirm the fungal etiology of atherosclerosis. This appears to be a quite valid conclusion since all of the other effective anti-cholesterol and/or anti-atherosclerotic therapeutic modalities share nothing in common except that they possess anti-fungal and/or anti-mycotoxin activity. Diseases of unknown etiology, which respond to anti-fungal-effective drugs, suggest the probability that they have a fungal origin, particularly when there is no other proven explanation as to how the drug is working. Table 2-2 provides a number of human diseases, which so respond and suggest a fungal or mycotoxin origin.

ENVIRONMENT, FOOD CHAIN and STORED FOOD

Fungi grow all over this planet. They are found in the soil, on trees and in water. Their spores travel throughout the lands by the winds from the four corners of our world. Biosensor testing conducted by the U.S. military has resulted in an increase population of Aspergillus niger on homes, trees and other materials in various areas of the United States of America.⁸

Over the last decade, starting in the 1990's, research has implicated many toxin-producing fungi, such as Stachybotrys, Penicillim, Aspergillus and Fusarium species, to indoor air quality problems and building related illnesses. Inhalation of mycotoxin producing fungi in contaminated buildings is the most significant exposure, however, dermal contact form handling contaminated materials and the chance of ingesting toxin containing spores through eating, drinking and smoking is likely to increase exposure in a contaminated environment. Recent advances in technology have given laboratories the ability to test for specific mycotoxins without employing cost-prohibitive gas chromatography or high performance liquid chromatography techniques. Currently, surface, bulk, food and feeds, and air samples can be analyzed relatively inexpensively for mycotoxins.

Homes that have been damaged by water or have had improper construction of ventilations systems have become infected with fungal overgrowth and biofilms, which resulted in bacteria, algae and fungi growing together as a communal colony with microtubules connecting to each other to exchange nutrients. Thus, creating the most toxic forms of mycotoxins, endotoxins, and exotoxins with the potential of forming DNA plasmids in mycoplasma, with mutated RNAi sub-mutated forms of fungi genes.^{9, 10}

The most toxic forms of fungi, mycotoxin is coming from our food itself, which is characteristically present in stored and fermented food. Pesticides used on cereals as a fungicide, such as benomyl have potentated the mycotoxin in selective genes. In 1987 at Yale University, Karl Hager and Mike Plamann performed a very important study, which was based on the plasmid pH303 and its derivatives integrated at his-3 by a single crossover. When introduced to benomyl, the mutant allele of his-3(1-234-723) was present in the genome, and its mutation was mapped to be somewhere downstream of the Sall restriction site. A cloning will occur at a higher transformation frequency using linear than using circular DNA, and the transformation frequencies are independent of the mating type of the host.¹¹

If food is loaded with fungi, then the myctoxin concept is fully operative and the disease-producing potential is more than obvious.

This important question of how much fungal colonization of food exists is answered by the most recent reported mycological study of some quite representative foods; corn kernels, peanuts, cashew nuts and copra (dried coconut). Table 3-3 demonstrates the remarkable degree of fungal colonization of the interior of corn kernels and peanuts.¹²

Humans who eat these foods are ingesting both the toxicogenic fungi and their mycotoxins. These fungi are capable of surviving in the intestinal stream where they may continue to produce their toxins.

Similarly, animals fed fungal colonized/mycotoxic feed are not only at risk of developing mycotoxicoses, their meat and their fat, constitute another vehicle for human exposure to excessive mycotoxin intake. Animal fat is increasingly being documented to be a major risk factor for a number of human cancers and atherosclerosis. It must be noted that fat, stores polycyclic organic xenobiotics and they are highly lipid soluble. They concentrate in fat depots, which results in low plasma levels and extended half-lives. These same compounds are known to cause distinct mutations. When cattle were accidentally fed contaminated feed in Michigan by PBB's in 1973, these compounds became stored first in fat deposits of the cows and then, via milk fat, bioaccumulated in fat stores of the people of Michigan, where PBB's can still be detected. While there is no known effect of PBB's at the storage site, this store is a potential hazard since mobilization during starvation or other stress could lead to efflux into the bloodstream with subsequent redistribution and toxicity. Similarly, patients treated for acute exposure to organophosporous pesticides may be released from the hospital and later suffer a relapse due to mobilization of the insecticide from fat stores.¹³

Mycotoxins have been documented to cause a number of specific types of diseases and very specific organ lesions both in animals and in humans. Table 4-4 provides a summary of some of this documentation.

DISEASES ASSOCIATED WITH VARIOUS MYCOTOXINS

Aflatoxin

Aflatoxin is one of the most potent carcinogens known to man and has been linked to a wide variety of human health problems. The FDA has established maximum allowable levels of total aflatoxin in food commodities at 20 parts per billion. The maximum level for milk products is even lower at 0.5 parts per billion. Primarily Aspergillus species fungi produce aflatoxin.

Ochratoxin

Ochratoxin is primarily produced by species of Penicillim and Aspergillus. Ochratoxin is damaging to the kidneys and liver and is also a suspected carcinogen. There is also evidence that it impairs the immune system.

T-2 Toxin

T-2 Toxin is trichothecene produced by species of Fusarium and is one of the more deadly toxins. If ingested in sufficient quantity, T-2 toxin can severely damage the entire digestive tract and cause rapid death due to internal hemorrhage. T-2 has been implicated in the human diseases alimentary toxi aleukia and pulmonary hemosiderosis. Damage caused by T-2 toxin is often permanent.

Fumonisin

Fumonisin is a toxin associated with species of Fusarium. Fumonisisn is commonly found in corn and corn-based products, with recent outbreaks of veterinary mycotoxicosis occurring in Arizona, Indiana, Kentucky, North Carolina, South Carolina, Texas and Virginia. The animals most affected were horses and swine, resulting in dozens of deaths. Fumonisin toxin causes "crazy horse disease", or leukoencephalomalcia, a liquefaction of the brain. Symptoms include blindness, head butting and pressing, constant circling and ataxia, followed by death. Chronic low-level exposure in humans has been linked to esophageal cancer. The American Association of Veterinary Laboratory Diagnosticians (AAVLD) advisory levels for fumonisin is horse feed is 5 ppm.

Vomitoxin or Deoxynivalenol (DON)

Vomitoxin, chemically known as Deoxynivalenol, a tricothecene mycotoxin, is produced by several species of Fusarium. Vomitoxin has been associated with outbreaks of acute gastrointestinal illness in humans. The FDA advisory level for vomitoxin for human consumption is 1 ppm.

Zearalenone

Zearalenone is also a mycotoxin produced by Fusarium molds. Zearalenone toxin is similar in chemical structure to the female sex hormone estrogen and targets the reproductive organs.

Citrinin

Citrinin is a nephrotoxin produced by Penicillium and Aspergillus species. Renal damage, vasodilatation, and bronchial constriction are some of the health effects associated with this toxin.

Alternariol

Alternariol cytotoxic compound derived from Alternia alternata.

Satratoxin H

Satratoxin H is a macrocyclic tricothecene produced by Stachybotrys chartaru, Trichoderma viridi and other fungi. High doses or chronic low doses are lethal. This toxin is abortogenic in animals and is believed to alter immune system function and makes affected individuals more susceptible to opportunistic infection.

Gliotoxin

Gliotoxin is an immunosuppressive toxin produced by species of Alternaria, Penicillium and Aspergillus.

Patulin

Patulin is a mycotoxin produced by Penicillium, Aspergillus and a number of other genera of fungi. It is believed to cause hemorrhaging in the brain and lungs and is usually associated with apple and grape spoilage.

Sterigmatocystin

Sterigmatocystin is a nephrotoxin and a hepatotoxin produced by Aspergillus versicolor. This toxin is also considered to be carcinogenic. Other mycotoxins include - Penicillic acid, roquefortine, cyclopiazonic acid, verrucosidin, rubratoxins A and B, PR toxin, luteoskyrin, cychlochlorotine, rugulosin, erythroskyrine, secalonic acid D, viridicatumtoxin, kojic acid, xanthomegnin, viomellein, chaetroglobosin C, echinulin, flavoglaucin, versicolorin A, austamid, maltayzine, aspergillic acid, paspaline, aflatrem, fumagillin nigragilin, chlamydosporol, iscotrichodermin and many more. As previously discussed there are many mycotoxins that can cause adverse health effects and even death in humans. These synergistic effects of exposure to multiple mycotoxins simultaneously are very poorly understood. Even more poorly understood are the by-products of mycotoxin degradation, particularly under the influence of strong oxidizing agents such as sodium hypochlorite and/or ozone, agents frequently used or misused by hazardous materials personnel or remediation remediators in industry. More research is required in this field to better understand the relationship of fungal contamination, relative humidity, temperature and ventilation in fungal growth in buildings and on building substrates as they relate to disease.¹⁴

VOLATILE FUNGAL METABOLITES

During exponential growth, many fungi release low molecular weight, volatile organic compounds (VOCs) as products of secondary metabolism. These compounds comprise a great diversity of chemical structure, including ketones, aldehydes, and alcohols as well as moderately to highly modified aromatics and aliphatics. Cultural studies of some common household molds suggest that the composition of VOCs remains qualitatively stable over a range of growth media and conditions. Furthermore, the presence of certain marker compounds common to multiple species, such as 3-methylfuran, may be monitored as a proxy for the presence of a fungal amplifier.¹⁴ This method has been suggested as a means of monitoring fungal contamination in grain storage facilities. Limited evidence suggests that exposure to low concentrations of VOCs may induce respiratory irritation independent of exposure to allergenic particulate. Volatile organic compounds may also arise through indirect metabolic effects. A well-known example of this is the fungal degradtion of urea formaldehyde foam insulation. Fungal colonization of this material results in the cleavage of urea from the polymer, presumably to serve as a carbon or nitrogen source for primary metabolism. During this process formaldehyde is evolved as a derivative, contributing to a decline in Indoor Air Quality.¹²

INTEGRATIVE HEALTH CARE TREATMENT

Many fungi, mycotoxins, and their VOC's are at a level of detection within the human body that is very hard to determine at relatively low costs. Tissue samples of blood, urine and even direct organ/tissue biopsy will determine the presence of a fungi, mycotoxin and/or their VOC's. To kill fungi and remove other substances it is necessary to look at a variety of treatment modalities. Current, anti-fungal formulations have been developed to address specific fungal infections. In many cases it is very hard for the healthcare provider and physician to determine what species of fungi was present that created what specific mycotoxin, which is a billion dollar revenue to the pharmaceutical industry.

In AIDS patient's fungal infections have been observed in tissue biopsy reports to be growing within the tissue and this causes great health risks to the patient. The use of far infrared as a treating modality can address the electromagnetic spectrum in micron and micrometers (nano level), which would be an ideal choice, in treating fungal infected patients. The far infrared segment of the electromagnetic spectrum occurs just below, or "infra" to, red light as the next lowest energy band. This band of light is as the next lowest energy band. This band of light is not visible to human eyes but can be seen by special cameras that translate infrared into visible colors. We can, however, feel this type of light, which we perceive as heat. The sun produces most of its energy in the infrared segment of the spectrum. Our atmosphere has a "window" in it that allows infrared rays-in the 7 to 14 micron bands, with peak output at 10 microns.

Our tissues normally produce infrared energy for warmth and tissue repair. Tissue production of infrared energy is associated with a variety of healing responses. At times the infrared energy in our tissues may require a boost to higher level to ensure the fullest healing possible for tissue repair. Body tissues that need an infrared boost selectively absorb infrared rays, after boosting a tissue's infrared energy; the remaining rays pass onward harmlessly. This phenomenon is called "resonant absorption." Our bodies radiate infrared energy through the skin at 3 to 50 microns, with most output at 9.4 microns. Our palms emit infrared energy too, from 8 to 14 microns. Palm healing, an ancient tradition in China, has used the healing properties of infrared rays for 3,000 years. Yogis in India also employ palm healing and recommended it especially for relieving eyestrain.

An MPS Capsule from MPS, Inc. Seoul, Korea, which generates far infrared energy from special carbon fibers manufactured by Daiugin and high gem graded jade balls with far infrared proprietary technology; may be a future solution for individuals suffering from fungal infections. Its dome generates temperatures as high as 165⁰F and the spinal column area as high as 148⁰F. These temperatures are known to kill fungi and release VOCs that have a lower melting point, like benzene at 81⁰F.^{15, 16}

The use of activated charcoal has been recognized by the U.S. Environmental Protection Agency in their text, Recognition and Management of Pesticide Poisonings, 4th Edition, in absorbing volatile organic compounds (VOCs), which are the same type of compounds found in fungal metabolites.¹⁷ Activated charcoal is made from burnt coconut husk. It is able to absorb at a minimum 35 % of the VOCs found in the intestinal tract from reabsorbing into the blood stream. It does not absorb in other areas of the body were VOC's may accumulate, such as in the lungs, brain, liver and fat. Research conducted at the Korean Atomic Institute have shown that Kuh Sung YLS-95 (Trade Marks Bio-Oaky & Oaky Smoky) a liquid yielding high plant infrared, which is made from oak wood charcoal vinegar is highly effective in significantly reducing carbon tetrachloride in rats and ethanol in humans within one hour after exposure.¹⁸

CONCLUSION:

One could test the validity of how poisonous mycotoxins are by eating a handful of poison mushrooms, a species of fungus. However, it would be less fatal to realize that many forms of fungus produce mycotoxins, which are chemical substances that are toxic to man and other life forms. In addition, fungi produce volatile organic compounds (VOCs), which may bind to fat within in your body and cause internal re-exposure to the toxic effects of these compounds. Current, integrative technologies in the health care area have produced far infrared MPS Capsules and Kuh Sung YLS-95 (Trade Mark Bio-Oaky & Oaky Smoky) that will kill fungus and neutralize VOC's in other tissue organs within the human body respectfully. These technologies may be the answer to current biological weapons of mass destruction and the risk of exposure to biological pesticides by killing these microorganisms at micron (0.000,001) and nano (0.000,000,001) levels within our human body. Cellular detoxification and its remediation are on the break of a new horizon through terahertz, far infrared and subnano technologies.  
PART 2 - SEE TABLES