Origins of environmental sensitivities

The subject of environmental sensitivities is replete with controversies over the causes and mechanisms. This section examines debates over physical versus psychological causes, and whether sensitivities are allergies. Various proposed mechanisms and toxicological roots of sensitivities are also explored.

The controversies

One debate is focused on whether the origins of environmental sensitivities are psychological or physical. This was addressed extensively by Thomson in the report of the Ad Hoc Committee on Environmental Hypersensitivities,⁶⁰ noting that patients see "an attempt by physicians to take refuge in a psychiatric label whenever it is impossible to identify a biological cause for their illness." Regarding the polarized debate he noted, "Those who see the illness as simply a psychological manifestation can be said to be as inflexible as those who see it as strictly a biological disorder." Indeed, treating a patient from the neck-up or the neck-down is not consistent with the comprehensive biopsychosocial model used in medicine. This model recognizes that the body, mind and environment (social and physical) are all connected and important in determining wellness.⁸⁸

Physical or psychological origins

Although nasal biopsies of people with multiple chemical sensitivities have revealed tissue abnormalities and greater numbers of nerve fibres,^89,90 and symptoms induced by chemicals have been shown to be accompanied by elevated nerve growth factor,⁹¹ there are no consistently informative and non-invasive diagnostic tests (e.g. blood or urine tests) for environmental sensitivities. Consequently doctors base their diagnosis on patient-reported symptoms and triggers of sensitivities. Self-reporting is standard for psychological symptoms, bringing some to the conclusion that sensitivities may be psychologically based.⁹² This has broad implications for treatment, workplace accommodations, compensation and liability.^93,94

In 2003, authors who have written extensively on the psychological basis of sensitivities analysed and discussed the body of research regarding environmental sensitivities. They examined the physical and psychological theories according to the Hill Criteria (strength of evidence, consistency/replication, specificity, temporality, biological gradient, plausibility, coherence, experiment and analogy). According to their analysis, the physical basis hypothesis failed every criterion while the psychological hypothesis passed every criterion.^95,96 To reach this conclusion, they made assumptions about unreported results of other researchers, and re-analysed research data such as responses of people with sensitivities to inhalation challenges, neurological testing and brain imaging. The conclusions were also based upon classical understandings of toxicology (the limitations of this paradigm led to the formation of the National Center for Toxicogenetics within the US National Institute of Environmental Health Sciences).

Although some researchers believe that environmental sensitivities may have strictly psychological origins, a 1994 review of psychological studies found methodological and logical problems in the then-current psychological research.⁹⁷  Environmental sensitivity reactions to inhalation challenges may mimic panic disorder, which is classified as a psychiatric condition.^98,99 However, it is difficult to separate physiological from psychological anxiety responses.⁷² Neuropsychological tests that yield abnormal results among patients with environmental sensitivities also yield abnormal results among people with chronic fatigue syndrome¹⁰⁰ and exposure to neurotoxicants.¹⁰¹ Moreover, the only test that identified people with environmental sensitivities relative to healthy individuals, was one complex test of verbal memory.^101,102 Another recent study concluded that symptoms of heavy metal and solvent exposure were psychosomatic.¹⁰³ This conclusion was based upon a lack of correlation between claims of sensitivities and contaminant concentrations in workers’ urine. However, this relationship may not be evident because heavy metals and organic pollutants accumulate in fat, organs and bones, and individuals have variable metabolism and excretion.^104,105 This means that urine concentrations are not necessarily representative of body burdens.

Recent research with better defined patient populations concluded that psychiatric symptoms are more likely to stem from, rather than to cause, symptoms of environmental sensitivities.^106,107 Development of sensitivities usually pre-dates symptoms of depression and anxiety in people with sensitivities, with 1.4% of patients identifying problems before the onset of sensitivities and 38% reporting the development of depression, anxiety and other symptoms after sensitivities became apparent.¹² Although emotional and behavioural problems, including depression, are more frequently found in people with sensitivities and fibromyalgia than in the general population,¹⁰⁰ psychological symptoms cannot be accounted for by psychiatric illness alone.^108-111 People dealing with a poorly recognized chronic illness that affects their brain, impairs their quality of life and earning potential, and has impacts on family and friends, would be under psychological distress. They could be expected to report anxiety and depression.^29,60,112

Adding to the complexity are recent findings that environmental factors such as pesticides and moulds have been shown to be associated with symptoms such as depression and anxiety.^113-116

Other research shows that psychological interventions are not entirely effective. For example, cognitive -behavioural therapy, used to desensitize one to the fear of sensitivity to substances, only partially reduced symptoms in a single case.¹¹⁷ Medication and psychological interventions may be used to treat phobia or panic disorder,118 but for individuals with environmental sensitivities, lasting benefits have been achieved only by avoiding incitants.²⁸ In a survey of 917 people with multiple chemical sensitivities, tranquilizers and antidepressants were the least effective therapy and caused harm28 (possibly because of a genetically-determined inability to metabolize them¹⁶). In another study, psychological treatment of medically unexplained physical symptoms provided no additional benefit compared to care by a general practitioner.¹¹⁹ 

Physicians seeking the most efficient and effective treatments have found that when people with environmental sensitivities were placed in an uncontaminated environment in which their physical symptoms resolved, their psychological symptoms also resolved.¹²⁰ Successfully alleviating symptoms of sensitivities (with safe housing, workplaces, food, water, etc.) is necessary before other psychosocial interventions may be helpful.¹²¹ In a large patient survey regarding treatments, avoidance of incitants was reported to be the most effective strategy, followed by meditation and prayer to address the psychological aspects of the condition.²⁸

People may be genetically pre-disposed to sensitivities. As a result of genetic polymorphisms, some bodies have less effective enzymes for detoxifying chemicals and metabolizing drugs. This is more prevalent in patients with multiple chemical sensitivity ^{16-19,22,55,122} and in Gulf War veterans who became ill. ^20,21 Interestingly, these genes are also more common in children who developed leukemia1²³ (the very young are particularly susceptible because the immature liver has low enzyme levels¹⁹). In multiple chemical sensitivity patients, a higher prevalence of a gene that has been associated with a biochemical basis for panic disorder has been found.¹²⁴

This review indicates that physical factors contribute to environmental sensitivities. There remain many unanswered questions regarding sensitivities and the interplay between biochemical, neurological and psychological processes.¹²⁵ It is important for society to come to a common understanding, in order to offer the most efficient, effective care to people with environmental sensitivities.

Allergy/role of the immune system

Labelling of environmental sensitivities as "being allergic to everything" has also engendered controversy, and the role of the immune system is an area of ongoing research. People with environmental sensitivities often experience runny noses and reactive airways, with asthma-like symptoms, but this is not necessarily classic allergy.

The lay person may consider "allergy" to be equivalent to "adverse reaction," but medically speaking, "allergy" refers to a specific type of reaction in the body that induces inflammation. Allergies involve an immune reaction wherein exposure to an allergen (e.g. pollen, animal dander, bee venom, peanut protein) stimulates the immune system to produce immunoglobulin E antibodies. Re-exposure may induce a range of inflammatory symptoms from rash, hives, red eyes or runny nose, to asthma or life-threatening anaphylaxis. However, immunoglobulin E antibodies are not present in reactions to very low levels of formaldehyde.^126,127 Nevertheless, people with environmental sensitivities may also have conventional allergies and indeed exhibit more allergies than the general population, with considerable overlap between asthma and multiple chemical sensitivities.^14,15

Although sensitivities are not classic allergic responses, the immune system may nevertheless be affected. Anti-neural autoantibodies (antibodies that attack one’s own nerves) may develop in response to mouldy environments.¹²⁸ Hyper-reactivity induced by scents and chemicals is accompanied by elevated nerve growth factor,⁹⁰ and exposure to electromagnetic fields may affect immune response.⁶

Possible explanations

Chemical exposures

In recent history, Canadians have been exposed to a rapidly expanding number of new synthetic chemicals, with over 23,000 not assessed for health effects. In the workplace or elsewhere, chemicals may enter the body by ingestion, inhalation or absorption through the skin. People with environmental sensitivities frequently identify chemical exposures, either acute or chronic, as initiating their condition or "tipping them over the brink."^3,30,74 This is quite plausible because many people with sensitivities may be genetically less able to metabolize chemicals.^{16-19,22,55,122}

Healthy bodily functions depend upon chemical (e.g. hormonal) as well as electrical signals to keep all systems (e.g. circulatory, digestive, endocrine, respiratory and nervous systems) working harmoniously. Foreign chemicals can mimic signalling chemicals such as hormones (e.g. estrogen, thyroid hormones, testosterone), thereby sending the wrong messages or blocking their transmission. Chemicals may also inhibit or stimulate production of enzymes, disabling or skewing important biochemical pathways. Developmental neurotoxicity is becoming increasingly important in understanding the roles of chemicals in human development.^39,129

Natural or synthetic chemicals may also affect biochemical pathways and development via "epigenetics," whereby genes are marked to be "read" or "silenced." These changes may be passed to successive generations.^130,131

After the 2001 World Trade Center collapse in New York, firefighters and workers were exposed to a multitude of substances of varying toxicities. Many developed severe breathing difficulties, as well as environmental sensitivities and other symptoms identified in Table 7.¹³² In the 9/11 example, there is a concern that conditions may be ineffectively treated as post-traumatic stress, whereas symptoms were reported to diminish or resolve when a sauna detoxification regimen with anti-oxidant and essential fatty acid supplementation¹³³ was used to enhance elimination of contaminants.

Common synthetic chemicals have been measured in many tissues, at all stages of life.^{53,65,134-139} Biomonitoring (measuring contaminants in the body, as is done by the US Centers for Disease Control¹⁰⁴) is an emerging area of research into relationships between contaminant levels, exposure levels and health risks.¹⁴⁰

Canadian workers have varying body burdens of heavy metal and organic pollutants, and different natural abilities to metabolize and excrete chemicals, putting them at a wide range of risks of developing sensitivities or other health effects. Chemical sensitivities may predispose people to increased sensitivity to other factors such as electromagnetic radiation, and vice-versa.^6,141

Neural sensitization

The high prevalence of neurological symptoms in people with environmental sensitivities led to interest in "kindling" within the nervous system. Kindling is a phenomenon whereby repeated low level exposures to chemicals, or electromagnetic currents or fields eventually cause symptoms at levels previously tolerated.^142-144 In this process, neurochemical, behavioural, endocrine and/or immunological responses are amplified.

The limbic system is identified as a target for kindling. This is a basic part of the brain, governing autonomic functions that maintain biological homeostasis. It is involved with the sense of smell, sleep, emotions and behaviour, as well as learning and short-term memory. The limbic system can become sensitized to stressors, and once sensitized will react even to very weak stimuli,^143,145 eliciting symptoms as seen in environmental sensitivities. The limbic system of the brain is affected directly from the nose via the olfactory nerve, and by inhaled chemicals that bypass the blood-brain barrier.

Receptor sensitization

The chemical and electrical signals that govern body systems involve "receptors." When a normal body chemical such as a neurotransmitter binds with them, the receptor sites initiate cascades of reactions. These sites may become over-sensitized and initiate unwanted conditions when "activated" by contaminants such as volatile organic solvents, formaldehyde or mycotoxin.^146,147 For instance, vanilloid receptors (which respond to capsaicin in hot peppers) have increased activity in people with chemical sensitivities.146

Heightened sensitivity of gamma-aminobutyric acid (GABAa) receptors, as well as an abnormal cholinergic system,^f implicated in chemical sensitivities.^148,149 GABA is involved in neural transmission, affecting motor function, vision and anxiety (suggesting again a physiological link to psychological symptoms).

N-methyl-D-aspartate (NMDA) receptors are in the limbic system, as well as in many other tissues. Activation of NMDA receptors results in elevated nitric oxide and peroxynitrite (an oxidizing agent), which are prominent in inflammation.

Inflammatory cycle

It has been proposed that increased levels of peroxynitrite contribute to neurological sensitization, as well as to a cycle of chronic inflammation as seen in a range of diseases including fibromyalgia, chronic fatigue syndrome, post-traumatic stress disorder and multiple chemical sensitivity.^147,150 Mitochondria (the part of the cell where cellular energy is regulated), cellular membranes, and an important enzyme system for detoxification (cytochrome-P450) are all harmed by the elevated levels, with widespread biological consequences such as neurological disruption, pain, fatigue and organ dysfunction. This model also explains the clinically observed efficacy of the nitric oxide scavenger, vitamin B12, and various combinations of antioxidants in treating these chronic illnesses.

The inflammatory cycle theory offers a basis for hypothesis-driven research and development of treatments. It complements the theory that kindling may explain sensitization, and addresses not only the preponderance of neurological symptoms in environmental sensitivities, but also the broad range of other symptoms.¹⁵⁰

Overload

The "General Adaptation Syndrome" model underpins modern medicine, describing how the body responds to "stressors" (e.g. chemical agents, vigorous exercise, emotional loss). If the stress does not kill, initially there is a "flight/fight" response, then a period of adaptation and then resistance to the stressor. Eventually, if the stress continues for long enough, or there is a sudden surge of stress, adaptive mechanisms are exhausted. This brings generalized breakdown of body systems and non-specific illness.¹⁵¹ Recognition of these universal bodily reactions to stressors of all types, which are mediated via the pituitary/hypothalamus/adrenal axis, spawned the science of psychoneuroendocrine immunology.^152-154

Ashford and Miller described this scenario as "Toxicant-Induced Loss of Tolerance" (TILT), a disease paradigm affecting a broad cross-section of society, including veterans of war, workers in many professions and trades, and children in poorly ventilated or maintained schools.^3,73 This toxic overload is treated by reducing the number of stressors, including chemicals and allergens in the body, the surroundings, food and water, as well as electromagnetic fields, currents and radiation. Reduction of emotional stressors may also help.¹⁵⁵

Summary

The balance of scientific evidence and experience indicates that environmental sensitivities generally arise from physiological causes, although there are many neurological and psychological consequences. Physiological responses to environme ntal factors vary greatly among individuals, and individuals’ experiences must play an important role in determining treatments. Once environmental factors initiating and triggering environmental sensitivities are addressed with safe housing, workplaces, food and water, then psychosocial interventions may assist people. The comprehensive biopsychosocial model of medicine, treating the body, mind and environment, is therefore the most appropriate and effective framework for treating environmental sensitivities.¹²⁵ The most practical approach, which is consistent with the practice of modern medicine, is to minimize potentially harmful exposures in the workplace for the health of all workers. Once a person has exhibited sensitivities they will always be susceptible to recurrence. Even though they may well regain their health and productivity, this predisposition to environmental sensitivities is life-long.

f. The cholinergic system is the part of the brain in which acetylcholine is a neurotransmitter. This part of the brain is important for leaning and memory. It is damaged in Alzheimer’s Disease.