The Case of the Disoriented Professor

 Case shared by Dr. Lyn Patrick of EMEI

A  45-year old white female medical school Physiology Department Chair came into the office with the following complaints: severe fatigue, debilitating brain fog, severe sensitivity to odors, edema, multiple GI symptoms (gas, bloating, constipation, diarrhea, pain) of 4 months duration. These symptoms came on at the time that a toluene leak was discovered in a lab in her area of the medical school.  She had worked in the medical school environment for the prior 23 years of her research career and had been healthy with no conditions or problems prior to that. The building she worked in also had a traffic tunnel beneath the floor she worked on. 

Shortly after the leak was discovered, she developed hypertension, gastritis, extreme fatigue, debilitating memory loss and confusion, and metrorrhagia that lasted 3 weeks after onset of expected menses.

About 2 months later she collapsed at work, lost consciousness and was seen in the ER and released. 

She then came down with a flu-like illness (fever, body aches, malaise) that did not remit. Her blood toluene levels at that time (which she demanded be tested, they were not drawn previously) were 1.4 ng/ml (reference range < 1.0 ng/ml). The 95^th% (top 5%) values for toluene in the CDC NHANES cohorts are .17 ng/ml for children and .983 ng/ml for Black adults). She also had elevated urine hippuric acid (7,500 mmol/mol creatinine). She did not return to work at that point. 

She was referred to the Environmental Health Center Dallas for evaluation and treatment and arrived there 2 weeks later. At EHC-D she was placed in an environmentally clean environment for 5 days and then exposed to a small amount of airborne toluene through double-blind challenge testing in a chemically free booth. On exposure to toluene, she experienced facial flushing, dizziness and flushing in her arms. She also experienced confusion, tremors, and clumsiness during exposure. Neurologic assessment showed a significant worsening on neurologic exam and impaired visuoperceptual motor function after the exposure. She was put on an amino acid-based liquid diet that included glycine, taurine, and n-acetylcysteine (1-3 grams of each with total protein 70 grams/day) and daily sauna therapy. She was also treated with liposomal glutathione, IV vit. C and antioxidants (selenium, vit. A, vit. E) and was able to tolerate green tea, curcumin and sulforaphane in small doses that were gradually increased to standard daily supplemental dose. One month later her blood toluene levels had decreased to .8 ng/ml. She became asymptomatic 4 weeks into the treatment and stayed that way for 19 years of follow-up. She still was unable to enter the original building she worked in and has not returned to the medical center. 

Background and Discussion:

Toluene is a hydrophobic solvent found in car exhaust from gas combustion, paint thinners, cleaning agents, adhesives, nail polish, and gasoline and is the most commonly abused volatile substance worldwide due to it’s intoxicating effects (inhalation from a pressurized can is the most common method of abuse also known as “huffing”, “bagging” or “sniffing”).  It is a common component of urban air and found in drinking water contaminated due to proximity to waste sites. Toluene is hepatically metabolized by cytochrome P450 to benzoic acid, then hippuric acid and is excreted in urine; mostly within 24 hours, although some may remain in fat for 72 hours or longer. The loss of hippuric acid is accompanied by potassium loss in the urine and can lead to hypokalemia and metabolic acidosis.

So let’s dive into this known exposure case to see what it can teach us.  There are a few important questions that were not included in the case, that could apply to any situation in which there is a common exposure in a group of individuals (mold/mycotoxins, new carpeting, pesticide spraying, etc.).

-Did anyone else at work feel ill at the time the patient lost consciousness or have they now contracted a chronic illness?

-This individual already complains of increased sensitivity to odors, a hallmark symptom of chemical sensitivity. Does this individual have any single nucleotide polymorphisms in metabolically pertinent enzymes, like cypP450 2D6, that may have made her more vulnerable to solvent exposure? Sixty-three percent of patients seen at EHC-Dallas had significant levels of toluene in their bloodstreams. 

-Does this individual have any other solvent exposure sources? (pesticide formulations used in or around the home, new memory foam mattress, pillow or topper, family hobbies that involve glue, solvent-containing cleaning products, plug-in air fresheners, nail polish, hair dye, acrylic spray paint, or laundry products that contain solvents (fabric softener).

Does she have exposure to/ or a demonstrable body burden of other toxicants? (metals, pesticides, plastics, EMFs, mold). Total body burden evaluation is always relevant in any known debilitating toxicant exposure (the camel/straw/broken back theory). 

-The 95^th% (top 5%) values for toluene in the CDC NHANES cohorts are .17 ng/ml for children and .983 ng/ml for Black adults). This woman had a treatment follow-up level of .8 ng/ml. Is that low enough? Would you recommend ongoing treatment? What is an acceptable value of blood toluene in a chemically sensitive patient? The answer to that is: as low as humanly possible.

Some of the symptoms of solvent exposure are self-evident: confusion, brain fog, clumsiness, visuoperceptual motor functioning (remember alcohol is a solvent) but increased menstrual bleeding, GI symptoms, edema?

Dr. Rea and Patel explain that much of environmental sensitivity and illness is mediated through the hypothalamus. This triggering can be the result of many inputs (stress, pain, etc.) but a common one is olfactory stimulation (toluene has a strong noxious odor).  This signaling goes through the olfactory nerve, bypassing the blood brain barrier and entering the amygdala and on to the hypothalamus in the suprapopticohypophyseal nucleus where ADH is produced. ADH, a strong antidiuretic and arteriolar vasoconstrictive hormone, is then released through the pituitary into the bloodstream and on to the kidneys where it controls about 15% of water resorption. 

This is why chemically sensitive (and chemically exposed) individuals often respond to a reversal of their edema and normalizing of blood pressure as a result of a 5 day water fast while living and sleeping in a clean environment. It is not unusual that patients lose 8-10 pounds of water weight in 24-48 hours under these conditions. This is not because they are fasting, it’s due to the clearing effect that fasting and being housed in a clean unit has on their production of ADH.

This pituitary dysregulation can also affect LH, FSH, estrogen and progesterone and lead to everything from PMS to metrorrhagia. GI symptoms are also common with solvent exposure as a result of neurologic toxicity. 

The treatment protocol: avoidance, removal from the environment, and oral amino acid based liquid nutrition is specific to solvents: phase II metabolism of solvents necessitates amino acid conjugation using glycine, taurine and cysteine. 

Solvent exposure, along with pesticides and mold, has been identified as one of the top exposures that initiates chemical sensitivity. Toluene is a particularly difficult inducer of chemical sensitivity, once it is established it may be necessary to provide a clean environment for the person exposed to live a healthy disease-free life. This would involve water and air filtration and an indoor environment devoid of solvent exposure sources. 

Resources and Sources of Information for this Case:

Rea WJ, Patel KD. Reversibility of Chronic Disease and Hypersensitivity Vol. 4 The Environmental Aspects of Chemical Sensitivity. 2018  CRC Press.

Rea WJ, Patel KD. Reversibility of Chronic Disease and Hypersensitivity Vol. 1 Regulating Mechanisms of Chemical Sensitivity, pg 430-432. 2010 CRC Press

Crinnion WJ, Pizzorno J. Clinical Environmental Medicine. pg 785. 2019 Elsevier.

Crinnion WJ. Environmental medicine, part 2 – health effects of and protection from ubiquitous airborne solvent exposure.” Altern Med Rev. 2000 Apr;5(2):133-43.

El Safty A, Metwally FM, Mohammed Samir A, ElShahawy A, Raouf EA. Studying the effect of antioxidants on cytogenetic manifestations of solvent exposure in the paint industry.  Toxicol Ind Health. 2015;31(12):1087-94.

Carlson GP, Turner M, Mantick NA. Effects of styrene and styrene oxide on glutathione-related antioxidant enzymes. Toxicology. 2006 Oct 29;227(3):217-26.