Molds, Mycotoxins, and Human Health by R. Gray, M.D., M.P.H., C.I.M.E.

[Guest guest]

Molds, Mycotoxins, and Human Health

R. Gray, M. D., M. P. H., C. I. M. E.

There are two hundred thousand different molds and fungi. They have been

present on this planet for 3 billion years, and certainly, many of us love

our bleu cheese. Most molds are quite harmless, aside from their tendency

to induce allergies in those of us who are prone to develop allergies in the

first place.

HOWEVER:

There truly were good reasons why we are warned in Leviticus: that if your

house be contaminated with plagues, mold and Leprosy, you should put the

contents in the middle of it, and set it aflame. The spores from

Stachybotrys chartarum (a.k.a. atra), a mold capable of producing some of

the most toxic substances known to human-kind, can survive temperatures up

to 500 degrees Fahrenheit, as well as acid, caustics, and bleach without

being destroyed. Spores from molds have been removed from

2,000,000-year-old sedimentary rock and grown when placed on appropriate

media. And, every nation that has developed biological warfare capability,

has harvested mycotoxins from molds, some of which are so toxic that

microgram quantities are capable of killing within twenty-four hours, while

being so completely metabolized that they are undetectable at autopsy.

From 1987 through the present Dr. Gray has developed a reasonably uniform

database on 350 patients with exposures to a variety of haptogenic

(immunologically reactive), xenobiotic (toxic) compounds, including 75

patients with confirmed exposure to toxigenic structural molds. These

patients have been evaluated in the context of individual clinical

encounters, with the workup including standardized comprehensive Internal

Medicine Database questionnaires with an extensive Occupational History

gathering component, Environmental History gathering questionnaires, kindly

provided by Grace Ziem, M.D., Dr.P.H., direct interviews, physical

examinations, extensive laboratory testing including complete blood counts

with differentials (CBCs), comprehensive metabolic profiles (CMPs),

arthritis and thyroid profiles, lymphocyte phenotype studies including total

white cell counts, total lymphocyte counts, T-cell and B-cell counts, T-cell

subsets, T-cell activation levels using both CD26 and HLA-DR markers,

evaluation of natural killer cell counts and functional status, audits for

auto antibody production, anti herpes viral titers, anti volatile organic

compound (VOC) antibody titers, evaluation of stimulated lymphocyte mitogen

response, and pulmonary function testing when indicated, electrocardiograms

and chest x-rays as indicated, neuropsychological evaluations, quantitative

electroencephalograms (QEEGs), and in the cases in which excessive mold

exposure was confirmed by environmental hygiene evaluations with

quantification and identification of the specific molds present, appropriate

audits were conducted for specific anti mold antibody levels. Excel

spreadsheets were prepared including the laboratory data of the confirmed

mold exposed patients evaluated between 1994 and February 2001. This

exercise revealed patterns of abnormalities consistent with what has been

reported in the literature in the last several centuries relating to the

adverse health effects of toxigenic molds and fungi in man and other

species. These include, but are not limited to, Alimentary toxic aleukia,

Dendrodochiotoxicosis, Kashin Beck disease, 'Usov's disease,'

Stachybotryotoxicosis, Cardiac beriberi, Ergotism, Balkan nephropathy,

Reye's syndrome, hepatocellular carcinoma, Pink Rot, and Onyalai.

Specifically, Dr. Gray's clinical evidence confirmed the presence of B-cell

proliferation, excessive T-cell activation, inhibition of suppressor cell

complement receptor sites, suppression of Natural Killer Cell populations

which are centrally involved in cancer cell surveillance and destruction,

and excessive mitogen suppression, confirmed by inhibition of stimulated

lymphocyte mitosis in the presence of extracts of pokeweed, concanavillin A

(Con-A), and phytohemagglutinin (PHA) implying the inhibition of immune cell

reproduction, generally considered necessary to mounting a competent immune

response. In short, the immune system is showing signs of being excessively

stimulated by the inhalation of respirable spores, and simultaneously is

being partially inhibited by the effects of the mycotoxins released by those

spores.

In addition, pulmonary function testing (PFTs) confirmed excessive small

airways obstruction, the hallmark of mold induced hypersensitivity

pneumonitis, and a review of the neuropsychological evaluations, and QEEGs

performed on the mold exposed individuals confirmed the presence of central

nervous system impairments consistent with what is expected based on

numerous animal and human toxicological studies found in the many peer

reviewed articles readily available in the extensive world literature on the

toxic effects of mycotoxins.

Several types of mycotoxins, including trichothecenes, ochratoxins,

patulins, and aflatoxins induce human illnesses, which resemble radiation

sickness and result from the random effects of being DNA " adduct formers. "

Adduct formers are compounds whose molecular size and configuration allow

them to insert themselves randomly into DNA, and RNA, thus resulting in the

inhibition of protein synthesis, bone marrow suppression, coagulation

defects and bleeding disorders resulting in nasal, pulmonary, and

gastrointestinal hemorrhaging, bleeding into the adrenal glands, uterus,

vagina, and the brain.

In addition, many mycotoxins are potently neurotoxic, producing central

nervous system effects including behavioral and cognitive changes, ataxia,

and convulsions. This has been extensively described in peer-reviewed

literature in the early and mid twentieth century-although this literature

is not readily accessible on computerized databases, such as the Medline,

and Toxline search systems, because these sources often do not include

titles before the 1960's. Nonetheless, mycotoxicosis has clearly been

demonstrated to have been the cause of several major human epidemics,

usually involving ingestion of foods prepared with mold infested grains and

cereals, or from the consumption of livestock which had been fed mold

infested feed. Inhalation and absorption of mycotoxins have also been

clearly demonstrated to be causative of human illnesses.

Throughout the course of almost thirty years of medical practice, Dr. Gray

has treated hundreds of patient with mold-induced diseases. Until 1994,

most of those patients were people with mold-related allergies and asthma,

and cases of symptomatic coccidiomycosis (valley fever). In 1994, he

treated a group of employees manifesting building related illnesses, which

were ultimately confirmed to have been caused by several molds, most

prominently Stachybotrus atra, Penicillium, Aspergillus, Chaetomium, and

several others, usually referred to as structural molds. He has since seen

several dozen patients with building-related mold exposures resulting in a

wide variety of illnesses.

The biological function of mycotoxins is to enhance the probability of

survival of the next generation of mold. The mycotoxins are typically

" packaged " in the spores with the DNA of the organism. This process almost

always takes place under adverse environmental conditions: when nutrient

substrates are becoming less available, or when arid conditions prevail. We

see this with regularity in the Sonoran Desert climate experienced in

Tucson. With every rain the molds grow. Within less than a day, when the

humidity returns to the teens (10 to 20% being the norm in the desert), the

ambient environmental spore counts reported by our local meteorologists

dramatically increases: it is a common species-specific survival mechanism.

When spores are forming, mycotoxins are being produced. The mycotoxins-many

of which are antibiotics or antifungal agents-provide an increased

probability that any given spore will be likely to survive in a very

competitive environment with many micro organisms competing for the same

ecological " nitch. " Because many of the molds also produce solvent carriers

they are not only a source of significant solvent exposure, but, whether the

mycotoxins do volatilize or not, the do aerosolize and become air born via

aerosol. In addition, the spores in which the mycotoxins often reside do

take flight as they are released from the hyphae, hair like processes of the

parent cell, and even the 7 by 4 micra Stachybotrys atra spore must be

considered respirable (able to penetrate to the respiratory surfaces of the

lung-the alveoli) because these particles tend to orient themselves parallel

to the long dimension of the progressively smaller bronchi as they travel

down to the lungs tiny air sacs. While the kinetics associated with

spherical particles dictates that only particles between 5 and 0.005 micron

are capable of penetrating to the alveoli, the size range of mold spores is

from 7 to 0.003 micron, and they are uniquely capable of penetrating to the

alveoli. Once having arrived in the alveoli, they stimulate a dramatic

immune response. This is also a site in which they are able to release

their mycotoxins, allowing them to be absorbed into the blood flowing

through the prolific capillary beds found adjacent to the air sacs. The

mycotoxins then circulate throughout the body.

Just as psilicybin containing mushrooms and lysergic acid (LSD) are capable

of inducing hallucinations, and cognitive distortions, a number of

mycotoxins are capable of causing both transient, and permanent

neurotoxicity. Approximately 70% of the patients with confirmed exposure to

toxigenic structural mold have been demonstrated to have significant

neurotoxicity. Neurological problems encountered among these patients have

included optic neuritis, multiple sclerosis, basal ganglion and midbrain

based movement disorders--developing in some cases within months of

occupancy of contaminated residences. In two female patients from Phoenix,

blindness was demonstrated in one or both eyes, and then within several

months of the onset of the optic neuritis, both were diagnosed with MRI

confirmed multiple sclerosis, first manifesting in the spinal cord of one of

them. Four of the patients in the same group were confirmed to have serious

movement disorders thought to be arising from midbrain structures. Another

patient was confirmed to have developed occulomotor nerve palsy on three

separate occasions, each time in conjunction with documented exposure to

Stachybotrus, and other structural molds and their associated mycotoxins.

Others were diagnosed with variable toxic encephalopathies by QEEG brain

mapping, neuropsychological testing, and specialized techniques measuring

specific quantifiable neurological parameters.

Toxic encephalopathy is a fluctuant neurological condition manifested by

cognitive impairments, which are the direct result of the recurrent and

paroxysmal activity of the immune system and the central nervous system

interacting with each other to cause episodic cognitive and neurological

dysfunction in the form of abnormal brainwave activity and associated

variable signs and symptoms of cognitive dysfunction such as memory loss,

dyslexia, word finding difficulties and attention deficit disorders. These

neurological abnormalities, which are triggered by exposure to

concentrations of haptogenic, xenobiotic, volatile, organic compounds at

sub-osmic threshold levels, have been demonstrated, by the work of Iris Bell

M.D., Ph. D., at the University of Arizona, as well as other researchers, to

trigger abnormal brainwave activity that is regionally specific, affecting

the temporal lobes bilaterally, the right parietal lobe and the frontal

lobes of the brain. These three central nervous system structures are

involved in memory function, spatial relations, and cognitive integrative

functions respectively. These effects are recurrent and can be demonstrated

through the use of multiple diagnostic modalities, including

electroencephalograms (EEGs), quantitative electroencephalograms (QEEGs),

PET scans, SPECT scans, and other objective neurophysiologic modalities.

When a patient is exposed to a haptogenic (immunologically active),

xenobiotic (toxic) trigger to which they are historically reactive,

abnormalities are observed on electroencephalographic tracings within

fifteen seconds of said exposure, even when administered in a double blind

fashion. It is now becoming clear that this paroxysmal activity can, in

fact, take the form of complex partial seizures, and often leads to

immediate, transient cognitive impairment, followed by a " post-ictal "

condition, characterized by excessive fatigue.

Because the victim of these episodes does not lose consciousness, as occurs

in grand mal seizures, they are often unaware that these episodes are

occurring, but an astute observer watching the individual would see what in

essence is described in the literature as an " absence seizure. " In many of

the patients who suffer from toxic encephalopathy that have been tested with

24-hour, ambulatory electroencephalograms, multiple seizures per hour in

some cases, and certainly multiple seizures in a 24-hour period have been

demonstrated.

Brain mapping, done by quantitative electroencephalographic techniques

(QEEG), also has demonstrated consistent abnormalities in several types of

brainwaves. This mode of analysis has become the clinically relevant

standard in the assessment of patients suffering from toxic encephalopathy,

and actually offers the potential for therapeutic intervention using

neurotherapy with QEEG-gated biofeedback techniques. Neurotherapeutic

intervention has been shown to reduce the frequency and severity of these

episodes, and may improve cognitive function and memory.

A wealth of literature in the field of Occupational Medicine has appeared

over a more than a century confirming the significance of molds in both

residential and workplace environments. Molds have long been known to lead

to the development of a severe debilitating lung disease known as

hypersensitivity pneumonitis. Hypersensitivity pneumonitis is an

inflammatory condition which involves inflammation in the smallest of the

airways in the lungs, triggered by exposure to commonly encountered volatile

organic compounds of a chemical nature, as well as several types of

biological dusts, pollens, mold spores and mycotoxins " packaged " within the

spores. The ensuing inflammation results in small airways spasms, and

obstruction occurring in regular and repetitive episodes. This condition

which causes shortness of breath, and often severe debilitating chest pain,

is generally treatable with medications commonly used for asthma, and is

only preventable by avoidance of exposure to the triggering agents such as

mold spores. Although the condition of hypersensitivity pneumonitis was

first described in association with mold spore exposure in conditions

varyingly described as reactive airways disease, silo filler's disease,

farmer's lung, bird fancier's disease--which rarely occurs among individuals

keeping a single bird as a pet, but frequently is seen among those

maintaining pigeon coups with hundreds of birds present at a time--and

byssinosis or " Brown Lung Disease " in cotton mill workers. If not treated

aggressively, hypersensitivity pneumonitis will lead to the progressive

development of emphysema. In the case of structural mold-exposed

individuals, treatment with antifungal medication, such as ketaconazole,

itraconazole, and/or fluconazole-each produced or derived from mold

mycotoxins themselves-may be appropriate and necessary.

There is allegedly " disagreement within the scientific community as to

whether the relatively large size of Stachybotrys spores prevents it from

penetrating to the deepest areas of the lung. " However, this controversy was

resolved by the documented presence of Stachybotrus spores in the alveoli

and small airways of the lung of an infant suffering and dying from

mold-induced hemorrhagic pneumonitis a rare lung disease, found to have

occurred in a series of nine infants in Cleveland, Ohio by Dr. Dore

Dearborn, who confirmed the presence of Stachybotrus mold in each of the

infants' homes. These cases were reported by the Centers for Disease Control

(CDC), in their 1998 Morbidity and Mortality Weekly Reports (MMWR). There

has been some controversy raised by some researchers claiming that they

cultured the organism from these homes, and were unable to detect mycotoxins

in the resultant cultures. The problem is that they are not acknowledging

that molds in general do not produce mycotoxins when they are growing under

" ideal " conditions, such as those that usually obtain in laboratory

settings. They generally produce their toxins when austere living

conditions bring about sporulation, for example when nutrients are depleted,

or when arid conditions prevail.

The clinical observations from the patients in Dr. Gray's practice who

presented between 1994 and the present with environmental hygiene

documentation of exposure to structurally-related molds in their homes or

workplaces provides clear evidence of the presence of consistent

abnormalities in the clinically relevant workup. These abnormalities

include, but are not limited to, the immunologic, pulmonary, and

neurological workup, that is clearly parallel to the findings in both human

and animal studies recorded in the local, national, and international

medical literature. Similar findings were reported in the case of Ron

-Melinda Ballard's husband-who suffered debilitating memory loss,

which, to a reasonable medical certainty, was causally related to the

confirmed and relevant mold exposure in their home. The congruency of the

findings in these cases, collectively have confirmed the presence of a

" clinical fingerprint " that allows for the clinical diagnosis of

mycotoxicosis-within reasonable medical certainty. It is quite clear, when

the clinical fingerprint is evident, that " but for the exposure to mixed

toxigenic structural molds " these constellations of illness would not be

occurring. One Tucson based neurotherapist, who has career long experience

treating patients with blunt head trauma, strokes, and toxin induced trauma,

stated that never in his experience has he seen entire families present

demonstrating cognitive deficits of such severity. The variety of

abnormalities reported is consistent with the random nature of the damage

induced by " adduct formers " discussed below. The random mutagenic events

encountered with mycotoxins is reminiscent of radiation induced damage, and

the same constellation of bone marrow suppression, interference with protein

synthesis resulting in failure to thrive, weight loss and weakness, easy

bruising, frequent nosebleeds, and increased susceptibility to infections,

skin lesions, and rashes is clinically similar.

In reply to the assertions that the symptoms reported by the victims of

toxigenic structural mold exposure, sick building syndromes, or chemical

hyper-reactivity are psychosomatic, or somatoform disorders, Ann off

(l994) clearly demonstrated the absence of any data supporting such

hypotheses. In addition, rebutting assertions of malingering by

" litigenous " victims of exposure to environmental toxins, powerful data has

been filed with the Federal Agency for Toxic Substances Disease Registry

(ATSDR) in relation to the sub-registry on the benzene exposed residents of

the Three Lakes Subdivision north of Houston, which clearly demonstrated

that there was no shift in the symptoms reported by this cohort of 1100

residents when they were surveyed both before and after litigation was filed

in that matter. Thus claims of somatoform origins of patients complaints

are seriously flawed, misleading, and biased, and represent an

unsubstantiated hypothesis which is at best without merit, and at worst

cruel, as it demeans patients who are suffering from serious, organic,

physiologic problems usually affecting multiple organ systems.

Mycotoxins produced by structural molds-meaning molds imported into the

residences, workplaces, and public buildings on the paper covering the

drywall, and other wood based composite materials-- often represent some of

the most toxic substances known to humankind. The molds imported on

building materials are not the same as molds commonly encountered in outdoor

environments. The wood chips, and wood pulp imported from the Amazon rain

forests bring with them their own varieties of mold spores. The climate of

" deregulation " that has prevailed since the early eighties has favored the

proliferation of new construction in which building codes requiring

pretreatment of building materials with anti-fungal agents have simply not

been adequately enforced. This in turn has led to circumstances, which when

coupled with " corner-cutting " structural defects, have led to the conditions

which favor water intrusion that has all to often allowed the appearance of

truly toxic levels of mold spores and mycotoxins, which are, in turn,

capable of inducing serious diseases resulting from the presence of agents

with the potential for damaging the human immune system, inducing allergies,

gastrointestinal disorders, skin disease, neurological disease, endocrine

disruption, birth defects, cancer, pulmonary, renal, hepatic, and general

metabolic disorders.

Treatment protocols for the problems seen must be individualized, and

carefully constructed, taken great care to avoid overuse of antibiotics with

infection mimicking inflammatory conditions. This is particularly relevant,

because inappropriate antibiotic use may foster further mold and fungal

growth in an already compromised host.

One of the most frustrating problems relating to dealing with patients

experiencing illness from exposure to structural molds, and bioaerosols from

gray water contamination is the inability to mobilize a proactive response

from public agencies. The issue is like the " hot potato. " In the apartment

complex alluded to above in the Phoenix area, when tenants complained to the

County Health officials, they came to inspect without the instrumentation

required for the detection of moisture or mold. And when attempts were made

to report cases of illness to the State Health Department, after being told

by a Deputy Assistant Director that the problem would be referred to the

Director of the Division of Epidemiology and Chronic Disease, no return call

was forthcoming. Similarly, when Dr. Gray raised the issue of structural

mold, which resulted in the closure of the Bella Vista Elementary School in

Sierra Vista with the Cochise County Board of Health--on which he served for

six years-- the only physician member of the Board opined that " mold was not

a public health issue! " Clearly, education is the order of the day.

R. Gray, M.D., M.P.H., C.I.M.E.

Preventive Medicine and Occupational Medicine, Board Certified

Internal Medicine, Emergency Medicine, and Toxicology, Board Prepared

Certified Independent Medical Examiner, and

Commissioner, Medical Direction Commission, Arizona State Division of

Emergency Medical Services.

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