Among the growing list of mysterious chronic illnesses is multiple chemical sensitivity (MCS). Easily mistaken for chronic fatigue syndrome, fibromyalgia, and biotoxin-related illnesses, MCS is difficult to diagnose. The associated symptoms are vague and run the gamut from cardiorespiratory to neurological and are capable of affecting nearly every organ system. MCS is unique from its masquerades in that exposure to low, nontoxic, levels of various chemicals is the trigger for many of its symptoms. With an unknown etiology, an unclear pathophysiology, and no known objective tests to detect it, MCS becomes underdiagnosed while continuing to plague a rising number of people. Its victims are equally frustrated as they seek a diagnosis and help, but often, in futility.

The chemicals known to trigger MCS most often include pesticides and volatile organic compounds (VOCs) such as perfumes, paint fumes, aerosols, cleaners, and formaldehyde out-gassing from furniture, workplace buildings, and new housing materials. Previously, it was thought that MCS only affected those with longstanding occupational chemical exposure, but it is now being seen in individuals with almost no history of overexposure to chemical hazards. As pesticide and chemical residues increasingly invade our air, soil, and water supply, it may become more important to consciously advise the use of air and water purifiers, the consumption of more organic foods, and the avoidance of chemical cleaners and body care products to prevent the development of MCS.

Immune dysfunction has been proposed as a component of MCS. When plasma cytokine levels were compared between 150 individuals with MCS and 148 healthy controls, plasma levels of interleukin-1β, -2, -4, and -6 were significantly increased, tumor necrosis factor-α was borderline significantly increased, and interleukin-13 was significantly decreased in the MCS group. These results suggest systemic inflammation and a deviating Th2-associated cytokine response not involving the common IgE-mediated mechanisms.

Neurological sensitivity is commonly reported among those with MCS. The oldest and most widely accepted theory explaining the pathophysiology of this reaction is the nitric oxide/peroxynitrite theory. It has been proposed that exposure to chemical toxicants activate the N-methyl-D-aspartate (NMDA) receptors in the hippocampus, leading to increased levels of nitric oxide and peroxynitrites. These free radicals generate oxidative stress and increased inflammatory cytokines, initiating low-grade systemic inflammation and neurological inflammation, as seen in MCS. Furthermore, nitric oxide is a retrograde messenger stimulating the release of neurotransmitters such as glutamate, causing excessive NMDA activity. A vicious cycle ensues. Other studies have supported the idea that increased NMDA activity is involved in MCS.

But why would chemical toxicants stimulate NMDA activity in some individuals, but not in others? Genetics may provide one explanation. Researchers have identified specific genetic polymorphisms that may be associated with inadequate chemical detoxification, increasing an individual’s risk of developing MCS. DNA samples were collected from 324 subjects; genes, which encode enzymes affecting the metabolic activation of a large number of xenobiotic compounds, were selected and analyzed in order to determine their influence on genetic predisposition chemical sensitivity. Analyzed genes included cytochrome P450 (CYP) 2E1, N-acetyl transferase (NAT) 2, glutathione S-transferase (GST) M1, GSTT1, GSTP1, low Km aldehyde dehydrogenase (ALDH2), and superoxide dismutase (SOD) 2. The results showed significant association between SOD2 polymorphisms, SOD2 allele frequency distribution, and MCS.

In another study of 203 test subjects and 162 controls, polymorphisms for cytochrome P450 (CYP) 2D6, NAT1, NAT2, paraoxonase-1 (PON1), and PON2 were genotyped. Significant differences in genotype distributions for CYP2D6 (which actives and inactivates toxins) and NAT2 (which bioactivates arylamines to protein-binding metabolites) were noted among those with MCS. The gene to gene interaction between CYP2D6 and NAT2 causes rapid metabolism of both enzymes leading to inadequate chemical detoxification and increased risk of MCS. Polymorphisms in PON1 alleles were also noted and an association between MCS and PON1 is supported by previous research that linked PON1 polymorphisms with neurological symptoms in Gulf War syndrome, purportedly caused by exposure to pesticides, vaccines, and other chemicals.

MCS often coexists with psychiatric conditions, loss of energy, difficulty in concentration, depressive feelings, memory disturbances, and fatigue, causing some to believe that this condition is psychogenic. However, increased NMDA activity is linked to memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury.

The first step in helping those with MCS is to correctly identify the condition, followed by understanding the role of inflammatory cytokines and neurotransmitter dysregulation in expressing its symptoms. Identifying genetic polymorphisms specific to MCS may be useful in confirming a diagnosis. Managing MCS must begin by reducing the overall toxin burden, found throughout the home and work environment, in foods, cleaners, and body care products. Next, it is important to focus on down-regulating the nitric oxide and peroxynitrite cycle. In Part 2, we will focus on specific ways to address this cycle to help manage MCS.

By Nicole Spear, MS, CNS

Related Webinar: Organic Acids Testing Part 3- Detoxification System: Detox, Methylation, and the Importance of Oxidative Stress