ClauDia S. Miller, MD, MS

For decades Dr. Miller has championed a new theory of disease to join the germ theory and the immune theory: Toxicant-Induced Loss of Tolerance (TILT). TILT explains the mystifying range of symptoms suffered by people with chemical intolerances. It is a two-step process. First, initiation involves acute or chronic exposure to environmental agents such as pesticides, solvents, or indoor air contaminants, followed by triggering of multi-system symptoms by exposure to small quantities of previously tolerated substances such as traffic exhaust, cleaning products, fragrances, foods, drugs, or food-drug combinations.

As part of her decades-long investigation of TILT, she has developed diagnostic instruments to help identify patients suffering from TILT-related intolerances. The Quick Environmental Exposure and Sensitivity Inventory (QEESI) is a 50-question survey. It is now the international reference standard for diagnosing chemical intolerance and TILT. It works because it was derived by applying factor analysis to observations by thousands of doctors and their millions of patients worldwide who reported developing multi-system symptoms and intolerances for chemicals, foods, and drugs following acute or repeated exposures to pesticides, remodeling/new construction, breast implants, and Gulf War chemicals—“xenobiotics,” that is, biologically foreign substances.

A survey of 10,000 US adults using the QEESI has shown that approximately 20% of respondents report intolerances, with food intolerances resulting in GI-related symptoms comprising a significant portion of that total. “TILTed” patients often report addiction and withdrawal symptoms related to formerly favorite foods including chocolate and pizza, and food-drug combinations like coffee, beer, and red wine.

She also developed a 3-question survey as a diagnostic screening tool, the Brief Environmental Exposure and Sensitivity Inventory, or BREESI. Respondents who respond positively to any of the questions are directed to take the full QEESI. You are invited to take the BREESI yourself below, and to follow the link above for the full QEESI, which includes several food-related questions.

Brief Environmental Exposure and Sensitivity Inventory

Instructions: Please answer these three questions by circling Yes or No.

1. Do you feel sick when you are exposed to tobacco smoke, certain fragrances, nail polish/remover, engine exhaust, gasoline, air fresheners, pesticides, paint/thinner, fresh tar/asphalt, cleaning supplies, new carpet or furnishings? By sick we mean: headache, difficulty thinking, difficulty breathing, weakness, dizziness, upset stomach, etc.

Yes No

2. Are you unable to tolerate or do you have adverse or allergic reactions to any drugs or medications (such as antibiotics, anesthetics, pain relievers, X-ray contrast dye, vaccines or birth control pills), or to an implant, prosthesis, contraceptive chemical or device, or other medical/surgical/dental material or procedure?

Yes No

3. Are you unable to tolerate or do you have adverse reactions to any foods such as dairy products, wheat, corn, eggs, caffeine, alcoholic beverages, or food additives (e.g., MSG, food dye)?

Yes No

Dr. Miller’s TILT research is rooted in observations dating back to the mid-twentieth century and beyond.

Soon after World War II, allergist Theron Randolph entered practice in Chicago and saw patients who reported food allergies. However, they were not typical IgE-mediated food “allergies.” Usual skin tests or laboratory tests did not explain his patients’ complaints of headaches, brain fog, cognitive and mood changes, muscle and joint pain, or digestive difficulties, nor did any known biological mechanism correspond with their symptoms.

Randolph placed them on rotary elimination diets in order to identify their food intolerances. He designed the first “chemically clean” environmentally controlled hospital units, in which patients fasted until their symptoms cleared, and then underwent food and low-level chemical challenges, one at a time, carefully spaced out over 2-3 weeks.

Following the introduction of synthetic chemicals, pesticides, and plastics after WWII, and energy conservation measures in the 1970s that reduced fresh air ventilation in buildings, he eventually described the outdoor and indoor air exposures that were triggering patients’ symptoms.

Today, it has become clear that a plethora of syndromes and unexplained illnesses are rampant, with many arising from exposures to xenobiotics. Dr. Miller’s work, which stems directly from Randolph’s legacy (she began her scientific journey as one of his patients), has shed enormous light on previously unrecognized and untreated disease.

Dr. Miller’s current research involves the relationship between xenobiotic exposures and disruption of the gastrointestinal microbiome, with an eye toward potential treatments involving pre- and probiotics.

Recently, she and her colleagues published a plausible and researchable biological mechanism for TILT—the activation and subsequent sensitization of mast cells, many of which are localized in the GI tract, where our greatest exposure to xenobiotics occurs.

Sensitization of mast cells (Stage I of TILT, Initiation) is followed by mast cell degranulation upon re-exposure to even minute amounts of previously tolerated xenobiotics, including inhalants, ingestants, and implanted materials. This corresponds to Stage II of TILT, Triggering. TILT appears to involve sensitization of our tissue- dwelling, “first responder” mast cells, which can in sub-second time set into motion the ancient cellular immune system (cell-mediated immunity). Allergists today are expert in diagnosing humoral immunity, which involves more readily measurable immunoglobulins like IgE, which circulate in the blood. Few practitioners today use elimination diets.

Dr. Miller will explain TILT and its association with food intolerances and the GI microbiome in her presentation to the World Asthma Foundation Microbiome First Summit, “Toxicant-Induced Loss of Tolerance for Chemicals, Foods, and Drugs: A Global Phenomenon.”

References

Nicholas Ashford & Claudia Miller. Chemical Exposures: Low Levels and High Stakes. Second Edition,
published 1998. John Wiley & Sons, Inc.
Miller and Ashford’s seminal work on chemical intolerance. The book is available for download
free of charge from the TILT website.
Miller CS, Mitzel HC: Chemical sensitivity attributed to pesticide exposure versus remodeling. Arch
Environ Health. 1995;50(2):119‐29. PMID 7786048 PubMed link
Miller CS: Chemical sensitivity: symptom, syndrome or mechanism for disease? Toxicology.
1996;111:69‐86. PMID 8711750 PubMed link
Miller CS: Toxicant‐induced loss of tolerance: an emerging theory of disease? Environ Health Perspect
1997;105 Suppl. 2:445‐53. PMID 9167978 Open Access article
Miller CS, Prihoda TJ. A controlled comparison of symptoms and chemical intolerances reported by Gulf
War veterans, implant recipients and persons with multiple chemical sensitivity. Toxicol Ind Health.
1999;15(3-4):386-97. PubMed link
Miller CS. Are we on the threshold of a new theory of disease? Toxicant‐induced loss of tolerance and its
relationship to addiction and abdiction. Toxicol Ind Health. 1999; 15 (3-4): 284-94. PubMed link
Miller CS. Toxicant-induced loss of tolerance. Addiction. 2001;96(1):115-37. PubMed link
Heilbrun LP, Palmer RF, Jaen CR, Svoboda MD, Perkins J, Miller CS. Maternal Chemical and Drug
Intolerances: Potential Risk Factors for Autism and Attention Deficit Hyperactivity Disorder (ADHD). The
Journal of the American Board of Family Medicine. July 2015, 28(4)461-470. Open Access article
Masri, S., Miller, C.S., Palmer, R.F. et al. Toxicant-induced loss of tolerance for chemicals, foods, and
drugs: assessing patterns of exposure behind a global phenomenon. Environ Sci Eur 33, 65 (2021). Open
Access article

Miller, C.S., Palmer, R.F., Dempsey, T.T.. Ashford, N., Afrin, L.B. Mast cell activation may explain many
cases of chemical intolerance. Environ Sci Eur 33, 129 (2021). Open Access article

Dr. Claudia S. Miller is an allergist and immunologist, author, instructor, and scientist noted for research in chemical intolerance, and development of tools for its diagnosis.

Miller is a professor of occupational and environmental medicine in the School of Medicine at the University of Texas Health Science Center at San Antonio. She is assistant dean for the school's M.D.-M.P.H. program, and vice chair of community medicine in the school's Department of Family and Community Medicine.