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Genetic Predisposition to Mold and Mycotoxin Illness
Practitioners such as Nathan and Anderson integrate the best of the Shoemaker Protocol with the recent findings by Brewer and their own clinical experience into a "best of all worlds" integrative approach.
Anderson has said many times that if he could only run one test, the HLA DR panel would be the one that he would choose because it provides him the most useful information from any single test. HLA stands for human leukocyte antigen and is found on the 6th chromosome; they are immune response genes involved in immune system recognition of an antigen. With the HLA DR results, one can look at the various combinations, which Shoemaker has identified and published, to determine if a patient is more likely to have a biotoxin illness from mold, Lyme disease, or other sources of biotoxins.
The degree to which one is made ill by mold and mycotoxins has been associated with one's genetic predisposition. In the overall population, the inability to adequately recognize and excrete mold toxins is about 25%. However, in those with chronic illness, this number is much higher.
When one's immune system cannot recognize and tag a biotoxin, the body is unable to effectively identify and remove that toxin from the system. Mycotoxins may be excreted via the kidneys into the urine or via the liver and bile into the feces. Further, enterohepatic recirculation of toxins is a common problem. As toxins are released in the bile and move through the gastrointestinal system, they are reabsorbed rather than excreted, as they are not recognized as harmful by the body. As a result, a person becomes and remains highly toxic unless the practitioner intervenes with an appropriate treatment protocol.
Not all people with chronic mold- and mycotoxin-associated illness will test positively with the RealTime Laboratories mycotoxin panel. There may be cases in which it is very clear that the person has an issue with mold, but the test may not identify mycotoxins. This is not to suggest that the test is not of value, but rather that the practitioner needs to know how to prepare the patient to optimize the results. In patients with an HLA DR type associated with mold biotoxin illness, Anderson has found an association with their compromised ability to excrete mycotoxins via the urine. More specifically, some patients need to have their urine tested after a sauna session, which can mobilize mold toxins, or a challenge test with glutathione to demonstrate that they do indeed have a high level of mycotoxins in their system. These patients require a treatment protocol that supports the excretion of mycotoxins in order to optimize the test results.
Everyone has two HLA alleles, one from the father and one from the mother. Four combinations are known to be the primary mold-susceptible types (7-2/3-53, 13-6-52 A/B/C, 17-2-52A, 18-4-52A). Anderson has found that when only one of the alleles has a primary mold-susceptible pattern, there may be a milder illness presentation associated with the mold and mycotoxin issues. This does not mean that the person won't have issues with ongoing mold exposure, but the treatment itself is often easier and the immune system often responds more appropriately when the body is dealing with this layer of the illness.
In contrast, a person with two mold-susceptible alleles will generally present with a more significant illness. They will be more likely to have a higher burden of intracellular mycotoxins. Until the detoxification systems are supported and working more effectively, these toxins may remain stuck inside the cells and thus may not be present when one is attempting to identify mycotoxins in the urine. Anderson has found that the more one's genetic predisposition is toward mold-associated biotoxin illness, the more additional detoxification support will be needed; further, more aggressive antifungal therapies may be needed to treat any molds that may be colonizing the body. He has observed that the likelihood of colonization and how deeply inngrained in the system the mold issue may be can also depend on how susceptible the person is to mold-related illness based on genetic predisposition.
In those with a single allele defect, the colonizing molds will attempt to grab and expand their territory in the body, but the immune system can still control this expansion somewhat and the surface area affected will be mild to moderate. In those with a double allele defect, meaning that both HLA DR patterns are mold susceptible, there is often much more significant colonization. These same people often had more frequent ear infections as children, developed asthma as teenagers, experience irritable bowel syndrome with bloating and gas, and have sinus infections. Females may have more common vaginal yeast infections and a higher propensity toward interstitial cystitis. There is far less ability for the body to respond to colonizing molds and to detoxify from their mycotoxins when a double allele defect is present.
Anderson's observation has been that those with a single mold-associated allele are often more easily treated for colonization. The treatment is more difficult than in a person with no mold-associated defects, but far easier than in a person with a double mold allele defect. In those with a double defect, a significant focus on detoxification is critical.
Beyond mold-susceptible or borrelia-susceptible HLA DR types, there are the multisusceptible HLA DR types (4-3-53, 11/12-3-52B, 14-5-53B). With respect to the mold component of the illness, Anderson has found that the multisusceptible HLA types are generally easier to treat than those with primary mold-susceptible patterns. His observation has been that those with the multisusceptible types are more affected by formaldehyde, petroleum-based chemicals, solvents, pesticides, and insecticides. These then become the focus of detoxification. In Anderson's world, detoxification is often the most important aspect of treatment.
Anderson has found that if one was born with a predisposition to mold biotoxins activated early on in life and later was infected with Lyme and associated coinfections, Lyme disease may be layered on top of the underlying fungal issue, and the fungal issue may not be what the person needs to address at that time. If the Lyme-related infections are what is drawing the attention of the immune system at that moment, it may only be after this layer is addressed that the fungal symptoms appear. In other words, some patients can have a significant mold load, but the practitioner may not be able to address that issue until the body is no longer being provoked by the Lyme layer.
Anderson has also observed that there can be seasonal influences that affect the primary layer that the body is dealing with. The immune system may have prioritized Lyme or a particular coinfection and may be ignoring underlying fungal issues; this can then flip in the winter when the rain hits. The increased exposure to molds in the winter may lead to the reprioritization of the fungal layer by the immune system. At that point, Anderson may need to shift from treating the Lyme-related issues to treating the mold issue. If mold allergy is present, this may also be seasonally influenced. The protocols are dynamic and must constantly be adjusted based on several factors such as the environment, new exposures, and what the immune system deems the dominant issue or pathogen.
While HLA DR testing is often very helpful, it is important to note that this is a genetic potential but does not represent whether or not the specific genes have been expressed. There may be additional gene correlations that are equally important but simply not yet known. So, while this is often a very useful guide, a less than optimal HLA DR result is far from the end of the story in terms of one's potential for recovery.
RealTime Laboratories Mycotoxin Testing
While RealTime Laboratories has offered mycotoxin testing since 2006, it has only recently become better known in the CFS and chronic Lyme disease communities, largely due to recent publications by Brewer. The test looks for aflatoxin, ochratoxin A, and trichothecene.
While the test has been a very positive addition to many practitioners' arsenal of diagnostic tools, special consideration must be given in order to optimize the results. Mycotoxins are generally stored intracellularly. For the toxins to be excreted in the urine, they have to leave the cell. In some of the sickest mold patients, if the mycotoxins are sequestered inside the cells, the level of mycotoxins in the urine may be very low and thus the test results may be negative. While the molds themselves live outside the cell, mycotoxins are intracellular poisons and must be released to be excreted from the body. Mycotoxins are lipophilic; that is, attracted to fat. One must open the detoxification pathways and facilitate the body's ability to release the stored toxins.
Prior to performing the urinary mycotoxin panel, the practitioner must ensure that the patient can detoxify in order to optimize the results. Some practitioners such as Nagy have found the use of far infrared (FIR) sauna (only when tolerated and not in patients with POTS or untreated adrenal insufficiency) prior to the urine collection to be very helpful.
Both Nathan and Anderson have observed some patients who tested negative after a FIR sauna challenge but later tested highly positive when supporting detoxification with liposomal glutathione. These patients had far more issues clinically than what the test showed, and using liposomal glutathione for a week or more prior to the test collection can assist in opening up the cell membranes and facilitating excretion of stored mycotoxins. Nathan has also observed marked increases in the mycotoxin levels after incorporating binders into a patient protocol. As antifungal therapy is initiated, additional mycotoxins may be released into the system which may result in higher levels of mycotoxin excretion. As the immune system and cellular health improve, this can further increase the level of mycotoxin excretion.
Anderson has found the RealTime mycotoxin testing to be very reliable and values the quantitative nature of the results. He often performs the test on patients when mold-related illness is suspected or when their HLA DR pattern leans toward mold-associated biotoxin illness. It gives him insight into how close to the surface the mold and mycotoxin components of the broader illness may be. In a chronically ill patient, the mold and mycotoxin component of the illness is often one of many layers. An attempt to look for mycotoxins in the urine is often the most productive when this layer comes to the surface.
While urine is the easiest specimen to obtain, the testing can be done on tissues, sputum, nasal secretions, and bronchial lavages. It is difficult to find mycotoxins in the blood, as the macrophages pick these up and move them quickly into tissue. Testing urine gives an overall picture of mycotoxins anywhere in the body, whereas nasal secretions would only reveal localized mycotoxin production. Thus urine is more widely used, as it provides insights relative to the broader body burden of mycotoxins.
One of the advantages of the RealTime testing is that after the initial panel has been run for a patient, subsequent testing to track progress of treatment is offered at a lower price for 18 months from when the initial test was performed.
In Nathan's experience with the RealTime testing, a very high percentage of his unusually compromised patient population shows some degree of mycotoxin burden. Some patients may not have current environmental mold exposures but may have had an exposure years earlier which led to ongoing colonization of the sinuses, gut, skin, lungs, or possibly dental cavitation areas.
Mold and Mycotoxin Illness Treatment
Both Nathan and Anderson have worked with patients with mold- and mycotoxin-associated illness for several years. They are intimately familiar with the Shoemaker Protocol and have used it with patients with positive results. While the Shoemaker Protocol is not the focus of this article and is not covered in the approach outlined here, a combination of approaches may be used. With the recent publications from Brewer on the potential for colonization of fungal mycotoxin-producing organisms, they have incorporated a treatment approach based on these newer findings.
There are three main steps:
- removing the exposure
- binding internal mycotoxins
- treating colonizing molds in the body
The first and extremely critical step in treatment is to ensure that there are no ongoing environmental exposures. This includes evaluating any environments where one regularly spends time, such as home, office, or school. Mold plates can be a reasonable initial screening option. Mycometrics ERMI testing is often very helpful, and working with a skilled environmental engineer may also prove beneficial. In order to optimize the treatment outcome, removing the exposure is key.
The second step is to consider binding internal mycotoxins. As previously discussed, one's genetic predisposition may play a role in one's ability to efficiently excrete mycotoxins from the system. In most chronically ill people, there are impairments in the detoxification system. Having appropriate binders on board minimizes this issue, as the toxins are then bound and more effectively excreted from the system. Binders should be started slowly and worked up over time in order to avoid an exacerbation of symptoms that can occur when too many toxins are being released in the system at once.
Cholestyramine has been used for biotoxin illness for years based on the work of Shoemaker and is often an excellent binder. It is believed by some to be a better option for ochratoxin than for aflatoxin or trichothecene. Welchol is another option that can be used as an alternative to cholestyramine for those who cannot tolerate it, though it is not as effective. Cholestyramine is best obtained from a compounding pharmacy in order to avoid sugar (which feeds yeast that produce more mycotoxins) and artificial sweeteners. Commercially available cholestyramine from conventional pharmacies may include large amounts of sugar or artificial sweeteners. It is generally taken 30 minutes before a meal, and no other supplements or medications are taken for at least 90 minutes after the meal to avoid reduced absorption of these items.
For aflatoxin and trichothecene, charcoal and bentonite clays are often the most beneficial binders. Calcium D-glucarate may support removal of trichothecene. Depending on the results of the RealTime Laboratories mycotoxin testing, both cholestyramine and additional binders may be used concurrently. Both charcoal and clays should be taken away from foods and other medications.
Chlorella is another useful binder that may be gentler when initially embarking on a mycotoxin-reduction protocol. Other binders that may be useful include zeolites, chitosan, modified citrus pectin, apple pectin, beta-sitosterol, glucomannan, diatomaceous earth, and others.
Anderson often selects a binder in relation to how frequently the patient has a bowel movement. Constipation is the enemy of any detoxification protocol. If the patient tends to be more constipated, he will generally avoid the use of cholestyramine or charcoal and instead consider chlorella or modified citrus pectin. Modified citrus pectin adds fiber, which often enhances bowel movements. If one tends to have diarrhea, cholestyramine or charcoal may be perfect options.
A combination product that some practitioners have found helpful is Advanced Naturals TOXIN AbsorbMax, which includes guar gum, glucomannan, activated charcoal, and citrus and apple pectins in one formula. A number of practitioners have found Supreme Nutrition Takesumi Supreme (carbonized bamboo) to be a beneficial binder. Pure Encapsulations CholestePure has been useful.
Other substances that have been found helpful in dealing with mycotoxins include alpha-lipoic acid and liposomal glutathione. Glutathione is a master detoxifier and one of the most powerful antioxidants in the body and has been shown to be very helpful in the detoxification of mycotoxins. It is involved in modulating the immune system and reducing inflammation. It supports the body in the removal of heavy metals. Nathan cautions, however, that for some patients, glutathione may provide negative feedback to the body's ability to methylate and should be used carefully. There are several excellent oral liposomal products that may be very helpful for supporting mycotoxin detoxification. These include QuickSilver Scientific Therasomal Glutathione, Researched Nutritionals Tri-Fortify Orange, Bulletproof Upgraded Glutathione Force, and ReadiSorb Liposomal Glutathione. NAC may be used as a glutathione precursor.
ReadiSorb consulting physician Timothy Guilford, MD, has researched the link between mycotoxins and glutathione and has found that mycotoxins block the formation of glutathione in the body. They interfere with the Nrf2 pathway and create an environment that allows them to persist. Glutathione levels are often low when TGF-b1 is elevated, which is common in mold patients. Low-grade fungal colonization in the sinuses can slowly deplete glutathione. Chronic infections can better persist in the body when glutathione is depleted, as glutathione is involved in intracellular killing of infections; thus liposomal glutathione can be a very powerful weapon in helping the body to deal with both infections and mycotoxins.
Supporting the body with drainage remedies that facilitate optimization of the detoxification systems and organs is another helpful strategy in removing toxins from the system. The liver, kidneys, and lymphatics are prime targets for this type of support. Nathan incorporates homeopathic drainage remedies from Pekana such as RENELIX (kidney support) and ITIRES (lymphatic support), especially in patients who have strong reactions to other attempts to detoxify the system and have a compromised ability to detoxify. He finds Beyond Balance TOX-EASE to be very helpful for this purpose.
Anderson follows a very specific order in approaching detoxification. First, the gastrointestinal system must be considered, as patients cannot adequately detoxify if they are constipated. Next, the liver, gallbladder, kidneys, and lymphatic system must be supported. Finally, toxins in the cells must be removed. However, you cannot start by attempting to dump intracellular toxins if the routes of elimination are not open, or you will make the patient more ill. "You simply add more traffic to the traffic jam," says Anderson.
Sweating via FIR sauna therapy is another excellent supportive detoxification modality that can be very effective in helping the body to rid itself of mycotoxins. In fact, the output of urinary mycotoxins has been shown to be higher after a sauna session, and this is a technique often used to maximize the mycotoxins identified through urinary mycotoxin testing.
The final step of the mycotoxin treatment protocol is treating colonizing molds in the body.
Mold does not technically live inside the body except in conditions such as end-stage cancers or HIV. Molds have the potential to colonize those areas considered outside membranes of the body, meaning that they are open to the external environment and separated from the blood by the epithelium, which acts as a barrier. Potential sites of colonization in the body for mycotoxin-producing fungi are the sinuses, gut, bladder, vagina, and lungs. Surprisingly, the lungs are often the least affected, as they contain lysosomes that serve as a protective mechanism against colonization. While the fungal colonization itself generally does not occur inside the body, the toxins produced by these organisms can enter the body and the intracellular compartments of the cells. Treatment for colonization of molds focuses primarily on the sinuses and gastrointestinal system.
For treatment of fungal organisms in the sinuses, an emerging option is the use of nasal amphotericin B, which helps to kill fungi used in conjunction with EDTA to dissolve biofilms. Biofilms are known to make treatment of chronic infections more difficult, as they serve as a protective barrier for the organisms that make it far more difficult to get the antimicrobial agents to where they need to go. Amphotericin B and EDTA are in generally used in separate preparations, with amphotericin B being used in the morning and EDTA in the evening or vice versa. Nasal itraconazole may be explored in some patients. The agents are delivered using an atomizer called the NasaTouch (available from ASL Pharmacy), which helps to deliver the compounds deep into the sinuses.
Treatment is started very gently, as one can have a very strong response that may make it difficult to tolerate the therapy if not done properly. Over time, the dosages are increased but only to the level that the patient can comfortably tolerate. A thick yellow or green mucus discharge has been reported in some patients and is believed to be a good sign.
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