Molds, Mycotoxins, and Human Health
Dr.Michael 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 Stachybotrus 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 Allison-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 Davidoff (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.
Michael 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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