Molds, Mycotoxins, and Human Health

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 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, andpulmonary 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 Stachybotrys 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 Stachybotrys 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. Dorr Dearborn, who confirmed the presence of Stachybotrys 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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