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Aug
Illness Tied to Petrochemicals’ Impact on Body’s Essential Mast Cells (immune system regulators), Study Finds
(Beyond Pesticides, August 22, 2023) A recently completed study (available in preprint before peer review) identifies the development of what the authors term “Toxicant-Induced Loss of Tolerance” (TILT), the constellation of symptoms associated with chemical exposures. The authors describe a two-part process. First, during initiation, a person is exposed at an acute level or repeated low-level doses to a toxicant, such as an organophosphate pesticide or a natural substance like mold, that triggers immune reactions from mast cells, which are crucial immune system regulators. Stage 2, or triggering, is when exposure to previously tolerated substances causes the mast cells to degranulate, or release many inflammatory molecules such as histamines and cytokines into the cellular environment. The work is spearheaded by Claudia B. Miller, M.D., immunology professor emeritus at the University of Texas Health Science Center at San Antonio, along with Nicholas Ashford, PhD, professor of technology at the Massachusetts Institute of Technology, and other researchers. Dr. Miller’s talk on the subject is found at Beyond Pesticides 2022 National Forum site (go to 7:50 time stamp).
Western medicine, for all its spectacular successes, has tended to view the human body as separate from its environment. Further, it divides the body into various systems and zones, which, though understood to be interrelated, have their own sets of symptoms, derangements, and diseases. In addition, the discipline of toxicology—especially regulatory toxicology—until very recently has been unable to account for exposure to multiple toxicants—pesticides, building materials, medical equipment, antibiotics, and molds—simultaneously or in series.
The last couple of decades, however, have begun to shed light on the consequences of exposure to many different chemicals that may affect different body systems and result in constellations of symptoms and disorders previously unconnected in the medical mind. Now people with what has been called Multiple Chemical Sensitivity (MCS) or Chemical Intolerance (CI) have a framework that begins to explain their problems. Some 15 percent to 36 percent of U.S. adults have reported symptoms of these disorders. Medical practitioners do not currently agree on the causes, development, or treatment of MCS/CI.
Dr. Miller finds that clinicians’ “failure to ask patients about possible initiating events has caused confusion concerning the origins of other comorbid conditions such as ADHD, autism, asthma, irritable bowel syndrome, migraine headaches, depression, anxiety, brain fog, and other cognitive and mood difficulties.” Moreover, Dr. Miller and colleagues note that in concurrent exposures to different toxicants, many symptoms are common to more than one, resulting in a “masking” effect. Once someone develops TILT, intolerances to structurally different chemicals may arise, ranging from pesticides and paints to anesthetics and hairdressing chemicals. Notably, women develop TILT more than men, possibly because women are more likely to use fragranced cosmetics, soaps, sprays, fragranced cleaning, and laundry products, usually in confined spaces. However, men are formally diagnosed with MCS more often, possibly reflecting medical gender bias.
In 2021 Beyond Pesticides reported on a study in which the researchers investigated initiating events by studying eight groups with chemical intolerance who had known exposures to different toxicants: EPA workers in offices where new carpet was installed; Gulf War veterans; casino workers exposed to organophosphate pesticides; pilots and cabin crews breathing aircraft oil fumes; World Trade Center first responders and others in close proximity to the buildings; breast and other implant recipients; people exposed to mold at home; and tunnel workers breathing benzene. Among these groups, volatile organic compounds (VOCs), which were present in nearly all the toxicants studied, were the most common initiators.
Some of the most egregious exposures were suffered by military members during the Gulf War, who were required to swallow pyridostigmine bromide to help defend against possible chemical weapons. This compound’s effects resemble those of organophosphate pesticides. Some 100,000 soldiers were directly exposed to sarin and cyclosarin when the U.S. blew up an Iraqi weapons depot. In addition, soldiers’ uniforms were saturated with lindane, an organophosphate pesticide and member of the Stockholm Dirty Dozen now banned for U.S. agricultural use but still allowed as a second-line treatment for lice and scabies. Permethrin, a pyrethroid insecticide, was also used on uniforms, and in combination with the insect-repellent DEET (also given to soldiers), it has neurotoxic effects.
In this previous study, the authors noted that the post-World War Two expansion of petrochemicals into pesticides, solvents, dyes, and fragrances mushroomed, and in the 1970s building construction became more airtight even as Americans spent more and more of their time indoors—the latter proportion now at 90 percent. This has resulted in more people being exposed to a staggering array of synthetic chemicals (defined by the authors as compounds not found in nature) and molds, which release naturally-occurring VOCs.
The authors of the current study also take the medical profession and research scientists to task for two things. Many clinicians dismiss chemical sensitivities as “Medically Unexplained Symptoms” or psychosomatic issues, sometimes labeled “idiopathic environmental intolerance.” Dr. Miller and colleagues are pushing to replace these terms with TILT. They provide two questionnaires, available on the University of Texas website, that individuals can complete and present the results to their medical caregivers. The advantage of TILT, they say, is that it provides both a suggested mechanism by which sensitivity is started and an explanation for how exposures to different toxicants result in common symptoms stemming from the activity of mast cells, which have broad influence over immune responses to many different challenges.
Scientific tunnel vision has affected the way medicine defines and diagnoses chemical intolerances. “Allergy and toxicology as currently practiced appear to have overlooked the two steps of TILT and the fact that toxic exposures can sensitize mast cells,” according to the current study. Mast cells are part of the innate immune system, which responds to acute or persistent infections or injuries. They signal other immune cells using the inflammatory biomarkers cytokines and chemokines. Dr. Miller and colleagues note that mast cells are present in large numbers in the gut, also home to trillions of microbes that are disrupted by antibiotics and pesticides. They add, “Future research should explore the mechanism by which exposures and/or alterations in the gut microbiome may compromise our ancient mast cells and innate cell-mediated tolerance.”
The study was based on 10,981 responses to a 2020 Survey Monkey questionnaire that used the same questions as those available on the University of Texas Health Science Center website. These ask participants about medical diagnoses, exposures to chemicals, antibiotic use, and the timing of the onset of their condition. The survey also asked the participant to identify what they believed was the condition’s cause.
More than half of the respondents were women, most of them under 60. Two-thirds of respondents were unable to identify an initiating event. For respondents reporting more than one initial exposure, each additional event tripled the chance they would have TILT.
Overall, a fifth of respondents met the study criteria for TILT. The most frequent initiating exposure was reported as mold, with pesticides second, and in decreasing order, new construction or remodeling materials, medical procedures, fires, and implants. Antibiotics used for long periods to treat infections in several organs were also associated with the onset of TILT.
The researchers stressed that we need “policies and practices that reduce initiating exposures as well as ubiquitous and often unavoidable triggers such as fragranced personal care, cleaning, and laundry products in multi-occupant housing, workplaces, medical settings, schools, places of worship, and all public buildings—literally anywhere air is shared.”
The current study does have limitations. Although it does have a large number of participants, it is based on individual self-reporting and not a direct measurement of the physiological processes associated with TILT. The participants were not randomly selected, and there was no control group. Also, only around half of the participants could attribute their initial symptoms to a specific event. Despite these constraints, the cumulative evidence Dr. Miller has produced finds that people in large numbers are suffering the consequences of the “exponential increase in exposures to toxicants derived from fossil fuels and biological sources, coupled with reduced fresh air in buildings” and the authors conclude that “TILT has become epidemic.” [Emphasis in original.]
Finally, Dr. Miller and colleagues emphasize that fossil fuels “are assaulting humans and other animal species both from within via mast cell sensitization and from without via climate change.” [Emphasis in original.] A low-carbon civilization, relying on ecosystem-level biochemistry rather than a single protein, an insidious and harmful source of energy and materials, might both survive climate catastrophe and enjoy a drastic improvement in human health.
For more information:
- Take the questionnaires used in the studies
- See a video from Beyond Pesticides’ 2022 Virtual Seminar featuring a talk with Dr. Miller and Kaipo Kekona, an indigenous Hawaiian working to restore traditional farming techniques
- Read a transcript of a talk given by Doris Rapp, MD published in our Pesticides and You newsletter
- Visit the University of Texas, San Antonio website for the Hoffman TILT program
- View a presentation by Dr. Miller at the Hoffman TILT program
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source: What Initiates Chemical Intolerance? Findings from a Large Population-Based Survey of U.S. Adults
