By Matt Pratt-Hyatt, PhD
Home is where most of us feel safe and is where we go to rest and recharge. Most of us never think that our homes could harm us, however, data show that homes are becoming more and more toxic. There are two reasons for this: the exponential increase in industrial chemicals and the increasing presence of mold growth in our homes. These two factors are leading to an unpublicized pandemic of patients with undiagnosed chronic illness. I personally have talked to hundreds of clients that have been sick for years and have not been given a proper diagnosis until testing revealed their underlying medical conditions. When I started testing people for mycotoxins, I was shocked by how many patients with chronic illnesses had high mycotoxins. However, having consulted with hundreds of practitioners in the last seven years, I have found a similar story time and time again.
Mold illness can come from two different sources. The first source, and the pathway that most doctors who practice traditional medicine understand, is the allergenic effect. These adverse health effects are produced by specific IgE reactions to fungal antigens. Molds that have been linked to these allergenic reactions include Aspergillus, Penicillium, and Chaetomium. Several recent studies have linked indoor fungal exposure to asthma; however, these studies haven’t shown if the amount or duration is the driving factor.1-3 Another study showed that 76% of patients with asthma have strong reactions to Aspergillus, Alternaria, Penicillium, and Candida.4 These are the types of reactions that are typical of people who have formed antibodies to these types of molds. The second and usually much more significant source is mycotoxins. Mycotoxins are small molecules that are produced by mold when they feel threatened.5 Think of this like the ink an octopus produces or when a skunk sprays someone. For most people mycotoxins at low levels are not problematic. Commonly, people are exposed to these low amounts of mycotoxins (normally ochratoxin and aflatoxin) in food. However, other mycotoxins are much more toxic. For example, the Trichothecenes, which are only found in water damaged buildings, are toxic. Trichothecenes are produced by Stachybotrys, otherwise known as black mold.6
The symptoms of mycotoxin exposure can be extremely divergent from person to person depending on a variety of factors: the amounts to which the patients were exposed, the age of the person, the sex of the person, their genetics, and other environmental factors. The bodily systems that are most commonly affected are immune system, nervous system/brain, and gut (Figure 2). Some of the common symptoms that can arise are fatigue, headaches, poor memory, abdominal pain, vertigo, and others (Figure 1). The symptoms of mycotoxin exposure are often mistaken for other diseases. Dr. Ruth Etzel, who specializes in environmental epidemiology, calls mycotoxin disease the “Great Masquerader of the 21st century” as its symptoms resemble multiple different diseases.7 Because of the variability of symptoms (even within the same family), mold and mycotoxin exposure can often go undiagnosed.
Clinical Testing
If you or a family member have had any of these symptoms, I would recommend first doing a urine mycotoxin test. There are three main types of testing for mycotoxins in patients, which are ELISA testing, LC/MS testing, and blood antibody testing. The first two are proven clinical tests while the third has not been proven useful and I would not recommend it. One thing to keep in mind while examining the results from these types of tests is that diet affects background amounts of mycotoxins. America’s food supply is heavily monitored by the USDA, which will prevent exposure for most of the population.8 However, in developing nations, which do not have the resources for an extensive monitoring effort, food can be a significant risk.9 Part of interpreting mycotoxin test results is understanding the norms you will see in background levels.
ELISA (enzyme-linked immunosorbent assay) testing works by developing antibodies to certain molecules (mycotoxins, in this case). The antibody is coated on the bottom of 96 well plates (See Figure 3). Samples are then added to the wells along with labeled mycotoxins (mycotoxins which are chemically bonded to agents, which will cause a color change). Any mycotoxins in the samples will compete with the labeled mycotoxins for a limited number of antibody binding sites on the bottom of the wells. The wells are then washed to eliminate mycotoxins not bound to antibodies on the plate. Finally, an agent is added that will interact with the labeled mycotoxins to cause a color change. This results in a reverse correlation between the amount of color in the well and the number of mycotoxins in the sample.
The second type of testing is liquid chromatography mass spectrometry (LC/MS). LC/MS works by injecting samples into a sample tube that drives the samples into a column, which separates the molecules by size and chemical properties. The sample then enters the mass spec, which measures the samples by size and then fragments the molecules. The fragments’ sizes are then measured. The sizes of the fragments and their amounts produce a spectrum that can be used like a fingerprint. This form of testing is extremely sensitive and extremely unlikely to provide any false positive results. However, the instrument’s exacting identification of exact mass is also the Achille’s heel of LC/MS when you are talking about mycotoxin testing. This is because there are many different enzymes that modify mycotoxins inside the body. Some of these enzymes include P450s, glutathione S-transferases, UDP-glucuronosyltransferases, and sulfur-transferases. These types of enzymes can modify between 50-90% of the total mycotoxins entering the body.10 If you don’t have standards for the metabolites, then the instrument will not know what patterns to look for and you won’t be able to measure those molecules. So, labs that measure mycotoxins by LC/MS could have a lot of variation in patient data from day to day or completely miss mycotoxins because of the modifications done to the mycotoxins by the detoxification systems in the body.
The third and final test type is the blood antibody test, which looks for the presence of immunoglobulin G (IgG) and E (IgE) antibodies to mycotoxins in the blood. IgG and IgE are antibodies produced by the body when a foreign antigen is present. IgG makes up about 75% of serum antibodies in humans. They are created by plasma B cells and their main roles are to activate the complement system to eliminate pathogens and to neutralize toxins. However, there are multiple reasons why measuring for these antibodies is noninformative. First, this technique is not used by experts in the field that measure mycotoxins. There are only a handful of clinical labs that utilize this method. Second, while mycotoxins can lead to the production of these antibodies, these antibodies will remain in the body long after the mycotoxins are removed. This makes the amount of antibodies uninformative when you are trying to determine if a treatment regimen is helping the patient. Third, it has been shown that many mycotoxins can interfere with how the body’s immune system functions.11
Home Testing
Treating patients with mold exposure has to include investigating their home, work, or school environments. Achieving good results with patients can be extremely difficult if they are still being exposed to mold and mycotoxins. If an individual’s mycotoxins in urine are high, there are three different common reasons. The first two instances involve having high mycotoxins in a home, school, or work environment. When analyzing a building, an inspector should focus on the 3 M’s, which are Moisture, Mold, and Mycotoxins. One important number is the water activity (aw) ( aw x 100 = % relative humidity at equilibrium) and the longer a material’s aw is over 0.75 the greater the risk for fungal growth.12 This explains why a significant portion of my mold clients reside in Florida, the Pacific Northwest (Seattle, Portland, Vancouver), and the Gulf of Mexico region (Houston and New Orleans), which are all high humidity areas. However, I have consulted on mold cases from every state in the US because construction and maintenance issues are not tied to a particular geographic region. Studies indicate that moisture damage and mold in the main living areas of the house are the most correlated with adverse respiratory effects.13-15 In addition, moisture damage in the building is correlated with other harmful outcomes for those that live/work in the building.16 These problems can be found in any part of a home/business/school; however, problems have been found in some areas more than others. Recent data shows we can see that a majority of problems are localized to the basement, attic, and bathrooms.17
The second M in the inspection process is mold. There are four main options for testing mold in an environment, which are spore traps, surface sampling, ERMI, and HERTSMI-2. I will detail out the strengths and weaknesses of all of these options. There are over 100,000 different species of molds and theses tests are looking at only a fraction of this amount; however, these tests were designed to test for the most common molds. The first two tests are spore traps and surface sampling. These utilize microscopes to identify which types of spores are in the home. The spore traps are set up throughout the home and will catch spores that are currently airborne in the home. However, if the mold is not currently releasing spores, then this test could produce false negative results. Surface sampling often refers to tape samples, where you place tape over a sample and then send the tape to be analyzed under the microscope. This is helpful in identifying visual molds that are in the home. The final two tests use PCR (polymerase chain reaction), which looks for DNA from fungal species in dust samples. The ERMI test is based on data from the EPA and the 2006 HUD American Healthy home survey. There are 36 different molds in these tests. There are 26 water damage molds and 10 common molds. The benefit of this test is that the client receives a lot of data. The downside is that some remediators scare clients with results that show high amounts of harmless common molds. One additional benefit of a ERMI is that you can calculate out a HERTSMI-2 score with these data.
HERTSMI-2 (Health Effects Roster of Type-Specific Formers of Mycotoxins and Inflammagens-2nd version) was developed by Dr. Ritchie Shoemaker to look at what he decided were the five most dangerous molds. The data from this report can be used to produce a score by using the spore counts from the five different species, e.g.: A spore count of Aspergillus versicolor of over 500 will be 10 points. Some individuals use a score of 5 and below as safe, others use a score of 10. The big downside of the HERTSMI-2 is that many pathogenic species of mold are left out of this analysis. For example, through my studies I have seen that Penicillium species are one of the most common sources of mold illness (also see table 1 and 2). Ochratoxin A, the most common mycotoxin found in humans, is produced by species of Penicillium.
The 3rd M for inspections is mycotoxins. As mentioned above, these are the toxins produced by mold. When mold feel threatened, the mold produces these metabolites. The types of toxins produced are dependent on the species of mold, the environment in which the mold is growing, and the mold’s food source. One of the most important parts of an inspection is the environmental mycotoxin assessment. Mycotoxins, which are molecules, are over 1000 times smaller than spores, which are cellular. Mycotoxins have the capacity to infiltrate areas of a building that spores may be unable to reach. In many instances, especially with Stachybotrys, you will not find mold spores in the main living area, but you will find mycotoxins that they produce. The reason why mycotoxins are easier to measure is because spores are multiple folds larger than mycotoxins and, in many instances, the spores are sticky. Because of these factors, spores can easily be trapped behind a wall but can still affect the inhabitants because of toxins they release. I would estimate about 30% of the time I have seen a house with normal mold levels on an ERMI but have dangerous levels of mycotoxins found in the living area.
If no mold or mycotoxins are found in current or past living areas but urine mycotoxins are high, then look for fungal infections into the sinus cavities. While infections and fungal biofilms have been reported in parts of the body, I am only reporting on known data published in PubMed. Fungal infections of the sinuses are also referred to as fungal rhinosinusitis. This classification actually accounts for a spectrum of diseases that usually are described by the causative organism such as penicilliosis (now known as taloromycosis), aspergillosis, fusariosis, etc. These infections are further broken down into either invasive or non-invasive,depending on whether the fungal hyphae invades tissues through the epithelium.18 The non-invasive types of infections frequently cause chronic rhinosinusitis (CRS; also known as chronic sinusitis), which is the presence of pain, facial pressure, and nasal drainage for at least 12 weeks.19 CRS is more frequently caused by bacterial sources, which is why practitioners often use antibiotics as a first solution. However, in the cases of fungal infections this is not helpful, and I have consulted on many cases where this actually worsened the patient’s symptoms. A paper by Brewer et al. shows that mold growing in the sinuses correlates with high mycotoxins in urine.20 Data that I have previously published found high correlation with three organic acid markers and patients with high mycotoxins. These markers were found in about 30% of individuals with high mycotoxins and usually correlated with patients whose high mycotoxins were persistent despite treatment. The markers were 5-hydroxymethyl-2-furoic, Furan-2,5-dicarboyxlic, and tricarballylic.21 These markers could be elevated either individually or at the same time.21
Treating patients with mold and mycotoxin exposure is difficult for multiple reasons. As detailed in this article the symptoms could be hard to identify, finding the source of exposure could be difficult to find, and the source of symptoms will be hard to detect with traditional tests. My suggestion is for practitioners to seek more training with groups such as the International Society for Environmentally Acquired Illness (ISEAI) and International Lyme and Associated Diseases Society (ILADS) and for patients to contact these groups to find practitioners in their area for help.
References
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2. Mendell MJ, et al. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence. Environ Health Perspect 119, 748-756 (2011).
3. Soeria-Atmadja D, Onell A, Borga A. IgE sensitization to fungi mirrors fungal phylogenetic systematics. J Allergy Clin Immunol 125, 1379-1386 e1371 (2010).
4. O’Driscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulm Med 5, 4 (2005).
5. Bills GF, Gloer JB, Biologically Active Secondary Metabolites from the Fungi. Microbiol Spectr 4 (2016).
6. Bertero A, et al. Fusarium Molds and Mycotoxins: Potential Species-Specific Effects. Toxins (Basel) 10 (2018).
7. Etzel RA, What the primary care pediatrician should know about syndromes associated with exposures to mycotoxins. Curr Probl Pediatr Adolesc Health Care 36, 282-305 (2006).
8. Park SH, et al. Effects of Mycotoxins on mucosal microbial infection and related pathogenesis. Toxins (Basel) 7, 4484-4502 (2015).
9. Smith LE, Stoltzfus RJ, Prendergast A. Food chain mycotoxin exposure, gut health, and impaired growth: a conceptual framework. Adv Nutr 3, 526-531 (2012).
10. Lyagin I, Efremenko E. Enzymes for Detoxification of Various Mycotoxins: Origins and Mechanisms of Catalytic Action. Molecules 24 (2019).
11. Kuhn DM, Ghannoum MA. Indoor mold, toxigenic fungi, and Stachybotrys chartarum: infectious disease perspective. Clin Microbiol Rev 16, 144-172 (2003).
12. Nielsen KF, et al. Mould growth on building materials under low water activities. Influence of humidity and temperature on fungal growth and secondary metabolism. International Biodeterioration & Biodegradation 54, 325-336 (2004).
13. Karvonen AM, et al. Moisture damage and asthma: a birth cohort study. Pediatrics 135, e598-606 (2015).
14. Kirjavainen PV, et al. Microbial secondary metabolites in homes in association with moisture damage and asthma. Indoor Air 26, 448-456 (2016).
15. Mustonen K, et al. Moisture damage in home associates with systemic inflammation in children. Indoor Air 26, 439-447 (2016).
16. Park JH, et al.Building-related respiratory symptoms can be predicted with semi-quantitative indices of exposure to dampness and mold. Indoor Air 14, 425-433 (2004).
17. Becher R, et al. Dampness and Moisture Problems in Norwegian Homes. Int J Environ Res Public Health 14 (2017).
18. Montone KT. Pathology of Fungal Rhinosinusitis: A Review. Head Neck Pathol 10, 40-46 (2016).
19. Dufour X, et al. Paranasal sinus fungus ball: epidemiology, clinical features and diagnosis. A retrospective analysis of 173 cases from a single medical center in France, 1989-2002. Med Mycol 44, 61-67 (2006).
20. Brewer JH, Thrasher JD, Hooper D. Chronic illness associated with mold and mycotoxins: is naso-sinus fungal biofilm the culprit? Toxins (Basel) 6, 66-80 (2013).
21. Pratt-Hyatt M, Shaw S. Biochemical Markers in the Urine Associated with Gastrointestinal Mold-overgrowth Are Linked with Elevated Urinary Mycotoxins in Patients with Suspected Mold Illness. The Townsend Letter, 31-38 (2019).
Dr. Matt Pratt-Hyatt received his PhD in cellular and molecular biology from the University of Michigan. He has over a dozen publications in well-known research journals such as PNAS and Cell Metabolism. He is focused on assisting with diagnosis and treatment of mitochondrial disorders, neurological diseases, chronic immune diseases, and more. He specializes in developing tools that examine factors at the interface between genetics and toxicology. His work is bringing new insight into how genes and toxicants interact and how that may lead to mental health disorders, chronic health issues, and metabolism disorders. He is currently working with The Mold Pros as scientific advisor and interface with practitioners.
