Although trace amounts of chemicals have been blamed for ill health, a new and comprehensive look at the evidence points the finger at anxiety
| 25 Sep 2021
Health
Health
MCGILL
Sometimes, science doesn’t give you the answer you wanted. You may be certain you know what is causing a mysterious phenomenon, but a well-done scientific experiment denies you that satisfaction and points you in an unexpected direction. Reality can be stranger than hypotheses.
Multiple chemical sensitivity (MCS) is one of those mysterious phenomena that science, when applied correctly, has the power to resolve. (As a side note, MCS can also be found under the larger umbrella of idiopathic environmental intolerance or IEI.) Put succinctly, it’s the complaint that some people are harmed by small concentrations of chemicals that the rest of us tolerate. Think perfumes, air fresheners, paints, scented products. It is a syndrome, a group of symptoms that always occur together, but those symptoms, to the great frustration of medical professionals, are often non-specific: they can have dozens and dozens of potential causes. They are commonly things like fatigue, headaches, and a general sense of not being well. The full list of potential symptoms involves every organ system in the body.
When a patient consults a doctor about non-specific symptoms and a battery of tests reveals nothing, it can be irritating. “The symptoms are clearly there,” the patient thinks, “why can’t my doctor find what’s causing them?” Which is why when they are given a diagnosis, even one that turns out to be wrong or fake, it feels reassuring. A diagnosis provides information about the condition and paves the way to meet other people with the diagnosis who can offer moral support and potential solutions.
I bring up MCS in this context because the question of what causes it has been addressed by a massive report that was published earlier this summer (in French only). In fact, to call it a report is to show modesty on behalf of its authors. At over 800 pages and with an emphasis on educating the reader about the many discoveries and technological innovations that helped researchers probe the mystery of MCS, it is a veritable textbook on multiple chemical sensitivity.
This textbook was commissioned by Quebec’s Ministry of Health and Social Services because of the magnitude of the problem in Canada. As the authors remark, the number of medical appointments made by people with MCS in Canada is much higher than that of a similar population. Quebec’s public health agency, the INSPQ, was thus tasked with summarizing the literature on the subject (over 4,000 papers and documents), and my hat’s off to the textbook’s many authors for this colossal work.
MCS was first described in 1956 and in the intervening 65 years, a number of hypotheses have been formulated to explain what its underlying cause may be. Could people with MCS have a genetic predisposition, a change in their DNA, that would trigger this sensitivity? We already know that certain changes can affect the activity of our enzymes tasked with metabolizing foreign substances. We can imagine a similar scenario in which molecules from a perfume end up causing some sort of toxicity because of the impaired function of an important enzyme. Genetic studies of MCS have so far produced contradictory results, in part because determining who belongs to the MCS group is not easy. There is no diagnostic test that can confirm someone has MCS. It is a diagnosis of exclusion, what is left after ruling out a long list of possibilities. So who participates in a genetic study of MCS can be just about anyone who self-identifies as having the syndrome, and this can fudge the data. So far, the INSPQ report concludes, the lack of reliability of these genetic studies means we cannot blame MCS on specific changes in the DNA. As we have seen with handedness, height, asthma and other traits, however, it may be that multiple genes all make small contributions to MCS, but this remains to be proven.
Another hypothesis is that these chemicals would have a neurotoxic effect: they would directly alter the normal functioning of the brain. Various mechanisms were proposed, including one poetically called “limbic kindling” which suggests that small, repeated exposures of the brain to a substance leads to a much-amplified response later on even in the absence of exposure. The idea is that these small, early exposures “kindled” or set fire to the electrical activity of the brain and the metaphorical fire is now self-sustained. While scientists seemingly agree that the limbic system—the parts of our brain involved in emotion, memory, learning, and motivation—indeed plays a role in MCS, they disagree on whether the dreaded chemicals are toxic to it or if the impact on the limbic system is due to the anxiety of anticipating the presence of the chemical. More on that later.
Then there is the immune system. Could MCS be an allergy? Laboratory tests proved negative. Could MCS be a type of immunodeficiency or an autoimmune condition like lupus? The data we have so far seem to disprove these ideas, although high levels of pro-inflammatory molecules seen with MCS (but not unique to it) may contribute to the condition.
The INSPQ textbook goes on to survey the remaining hypotheses—blaming oxidative stress, or inflammation inside the brain or the spinal cord, or the sense of smell itself—but while some of these systems are altered in some way in MCS, nothing could be pinned down as a specific cause. Studies on the sense of smell are particularly revealing, however. People with MCS who enrolled in these studies had no better detection threshold than people without MCS when it came to smells, thus ruling out a hypersensitivity of the nose, but surprisingly enough they were worse at identifying and distinguishing familiar smells. Not better; worse. Moreover, in a 2016 study, participants with MCS would start reporting symptoms before the volatile chemicals were even deployed. Faced with all of this information, the INSPQ report ends with the remaining hypothesis: that multiple chemical sensitivity is an anxiety disorder.
It’s worth highlighting the fact that people who suffer from an anxiety disorder are not “crazy.” Our brain is an organ, like our liver and lungs, and it can malfunction. There is an unfortunate stigma around mental health and a severe underfunding of services meant to address it. But anxiety, depression, bipolar disorder—these are as real as high blood pressure and asthma, and they have genuine and debilitating effects on the body. Summarizing the research on MCS, the INSPQ report proposes that chronic anxiety can explain all of the symptoms associated with MCS. Anxiety is characterized by the anticipation of a perceived danger, which leads the person to always be on the lookout for this supposed threat, thus creating a state of permanent stress. The perception of a threat, in this case, a chemical, arises through a bit of conditioning: if the chemical is originally detected when someone’s symptoms independently manifest themselves, an association is made which leads to a catastrophizing anticipation of the next exposure. Physical consequences, like insomnia, depression, and headaches, trickle down from this state of constant anxiety.
This is a real health issue, and the INSPQ proposes that specialized centres dedicated to MCS be set up to address this significant problem. While it is challenging to know how many people are affected by MCS given the lack of proper diagnostic tools, the scientific literature reveals numbers between 0.5 and 3% of the population when it is diagnosed by a medical doctor, and up to 32% (a third) of the population when it is self-diagnosed, with a higher risk being seen in women and in adults between the ages of 40 and 60. This is not a problem that can be ignored.
But blaming trace amounts of chemicals is simply not supported by the evidence at this point. If you cannot reliably tell when you are being exposed to the chemical; if you start reporting symptoms before the chemical is even released; if your brain is worse at identifying smells than the average person; if it has been shown that these chemicals, present in trace amounts, are not even absorbed by your body; then it is unlikely this chemical is responsible for the debilitating symptoms. This latest summary of the evidence points us in a different direction than the original name of the syndrome did, and while it will not please everyone, it paves the way for more effective treatments of a very real condition.
Take-home message:
Sometimes, science doesn’t give you the answer you wanted. You may be certain you know what is causing a mysterious phenomenon, but a well-done scientific experiment denies you that satisfaction and points you in an unexpected direction. Reality can be stranger than hypotheses.
Multiple chemical sensitivity (MCS) is one of those mysterious phenomena that science, when applied correctly, has the power to resolve. (As a side note, MCS can also be found under the larger umbrella of idiopathic environmental intolerance or IEI.) Put succinctly, it’s the complaint that some people are harmed by small concentrations of chemicals that the rest of us tolerate. Think perfumes, air fresheners, paints, scented products. It is a syndrome, a group of symptoms that always occur together, but those symptoms, to the great frustration of medical professionals, are often non-specific: they can have dozens and dozens of potential causes. They are commonly things like fatigue, headaches, and a general sense of not being well. The full list of potential symptoms involves every organ system in the body.
When a patient consults a doctor about non-specific symptoms and a battery of tests reveals nothing, it can be irritating. “The symptoms are clearly there,” the patient thinks, “why can’t my doctor find what’s causing them?” Which is why when they are given a diagnosis, even one that turns out to be wrong or fake, it feels reassuring. A diagnosis provides information about the condition and paves the way to meet other people with the diagnosis who can offer moral support and potential solutions.
I bring up MCS in this context because the question of what causes it has been addressed by a massive report that was published earlier this summer (in French only). In fact, to call it a report is to show modesty on behalf of its authors. At over 800 pages and with an emphasis on educating the reader about the many discoveries and technological innovations that helped researchers probe the mystery of MCS, it is a veritable textbook on multiple chemical sensitivity.
This textbook was commissioned by Quebec’s Ministry of Health and Social Services because of the magnitude of the problem in Canada. As the authors remark, the number of medical appointments made by people with MCS in Canada is much higher than that of a similar population. Quebec’s public health agency, the INSPQ, was thus tasked with summarizing the literature on the subject (over 4,000 papers and documents), and my hat’s off to the textbook’s many authors for this colossal work.
MCS was first described in 1956 and in the intervening 65 years, a number of hypotheses have been formulated to explain what its underlying cause may be. Could people with MCS have a genetic predisposition, a change in their DNA, that would trigger this sensitivity? We already know that certain changes can affect the activity of our enzymes tasked with metabolizing foreign substances. We can imagine a similar scenario in which molecules from a perfume end up causing some sort of toxicity because of the impaired function of an important enzyme. Genetic studies of MCS have so far produced contradictory results, in part because determining who belongs to the MCS group is not easy. There is no diagnostic test that can confirm someone has MCS. It is a diagnosis of exclusion, what is left after ruling out a long list of possibilities. So who participates in a genetic study of MCS can be just about anyone who self-identifies as having the syndrome, and this can fudge the data. So far, the INSPQ report concludes, the lack of reliability of these genetic studies means we cannot blame MCS on specific changes in the DNA. As we have seen with handedness, height, asthma and other traits, however, it may be that multiple genes all make small contributions to MCS, but this remains to be proven.
Another hypothesis is that these chemicals would have a neurotoxic effect: they would directly alter the normal functioning of the brain. Various mechanisms were proposed, including one poetically called “limbic kindling” which suggests that small, repeated exposures of the brain to a substance leads to a much-amplified response later on even in the absence of exposure. The idea is that these small, early exposures “kindled” or set fire to the electrical activity of the brain and the metaphorical fire is now self-sustained. While scientists seemingly agree that the limbic system—the parts of our brain involved in emotion, memory, learning, and motivation—indeed plays a role in MCS, they disagree on whether the dreaded chemicals are toxic to it or if the impact on the limbic system is due to the anxiety of anticipating the presence of the chemical. More on that later.
Then there is the immune system. Could MCS be an allergy? Laboratory tests proved negative. Could MCS be a type of immunodeficiency or an autoimmune condition like lupus? The data we have so far seem to disprove these ideas, although high levels of pro-inflammatory molecules seen with MCS (but not unique to it) may contribute to the condition.
The INSPQ textbook goes on to survey the remaining hypotheses—blaming oxidative stress, or inflammation inside the brain or the spinal cord, or the sense of smell itself—but while some of these systems are altered in some way in MCS, nothing could be pinned down as a specific cause. Studies on the sense of smell are particularly revealing, however. People with MCS who enrolled in these studies had no better detection threshold than people without MCS when it came to smells, thus ruling out a hypersensitivity of the nose, but surprisingly enough they were worse at identifying and distinguishing familiar smells. Not better; worse. Moreover, in a 2016 study, participants with MCS would start reporting symptoms before the volatile chemicals were even deployed. Faced with all of this information, the INSPQ report ends with the remaining hypothesis: that multiple chemical sensitivity is an anxiety disorder.
It’s worth highlighting the fact that people who suffer from an anxiety disorder are not “crazy.” Our brain is an organ, like our liver and lungs, and it can malfunction. There is an unfortunate stigma around mental health and a severe underfunding of services meant to address it. But anxiety, depression, bipolar disorder—these are as real as high blood pressure and asthma, and they have genuine and debilitating effects on the body. Summarizing the research on MCS, the INSPQ report proposes that chronic anxiety can explain all of the symptoms associated with MCS. Anxiety is characterized by the anticipation of a perceived danger, which leads the person to always be on the lookout for this supposed threat, thus creating a state of permanent stress. The perception of a threat, in this case, a chemical, arises through a bit of conditioning: if the chemical is originally detected when someone’s symptoms independently manifest themselves, an association is made which leads to a catastrophizing anticipation of the next exposure. Physical consequences, like insomnia, depression, and headaches, trickle down from this state of constant anxiety.
This is a real health issue, and the INSPQ proposes that specialized centres dedicated to MCS be set up to address this significant problem. While it is challenging to know how many people are affected by MCS given the lack of proper diagnostic tools, the scientific literature reveals numbers between 0.5 and 3% of the population when it is diagnosed by a medical doctor, and up to 32% (a third) of the population when it is self-diagnosed, with a higher risk being seen in women and in adults between the ages of 40 and 60. This is not a problem that can be ignored.
But blaming trace amounts of chemicals is simply not supported by the evidence at this point. If you cannot reliably tell when you are being exposed to the chemical; if you start reporting symptoms before the chemical is even released; if your brain is worse at identifying smells than the average person; if it has been shown that these chemicals, present in trace amounts, are not even absorbed by your body; then it is unlikely this chemical is responsible for the debilitating symptoms. This latest summary of the evidence points us in a different direction than the original name of the syndrome did, and while it will not please everyone, it paves the way for more effective treatments of a very real condition.
Take-home message:
-Multiple chemical sensitivity (MCS) is a chronic condition, often blamed on exposure to trace amounts of chemicals, that is accompanied by a wide variety of symptoms
-Since it was first described in 1956, scientists have investigated many hypotheses to explain how tiny concentrations of chemicals could affect people with MCS: hypotheses based on genetics, neurology, the immune system, the sense of smell, oxidative stress, and the mind influencing the body
-An 840-page report by Quebec’s public health agency summarizes the state of our knowledge on MCS and comes to the conclusion that trace amounts of chemicals are not to blame and that MCS is a type of anxiety disorder in which anticipation of a danger causes very real and debilitating physical symptoms
@CrackedScience
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