Chemical Intolerance October, 10, 2005
Researchers explore relationships between this
environmentally induced illness and addiction
Chemical intolerance, or as it was once known, multiple chemical sensitivity,
continues to be a serious health issue. Up to 6% of the U.S. population may
react so seriously to chemical exposures that the quality of their day-to-day
lives is affected. What causes this condition it still largely a mystery, and
there is no effective way to treat the problem.
The aim of the conference was to see if some of the research methods used to
study addiction could be employed to investigate chemical intolerance. Other
important issues included exploring the idea that people who are addicted to
drugs or alcohol may be more likely to become chemically intolerant and
whether certain genetic variances make individuals more susceptible to
chemical intolerance. Participants at the conference also considered whether
the disease mechanisms operating in alcoholism or drug addiction also apply to
Chemically intolerant individuals are those who, after exposures to often high
concentrations of compounds--such as pesticides, solvents, cleaning agents,
toxic molds, or volatile organic compounds--begin to experience adverse
effects from exposures to low levels of these substances. As time goes on,
they begin to react to exposures that never bothered them before, such as
fragrances, cleaning agents, tobacco smoke, alcoholic beverages, medications,
caffeine, and traffic exhaust.
In key respects, "chemical intolerance looks like the flip side of
addiction," said conference organizer Claudia S. Miller, professor of
environmental and occupational medicine at the University
of Texas Health Science Center, San Antonio. "Addicted individuals
seek repeated hits of a substance," she explained, "while the
chemically intolerant shun many of the same substances. But the reason for
these seemingly opposite behaviors may well be the same--to avoid unpleasant
withdrawal symptoms." Further, she said, "similar neurotransmitter
pathways and pathophysiology may underlie both addiction and chemical
Epidemiological studies show that 3-6% of the U.S. population suffers from
chemical intolerance severe enough to be disabling or compromise their quality
of life, Miller said. A 1994 report prepared for the European Commission
concluded that chemical intolerance is found in at least nine European
countries as well, though no studies have been done to determine its
prevalence in Europe.
The chemically intolerant have one or more of a wide variety of symptoms.
These include skin disorders, memory and concentration difficulties,
depression, debilitating fatigue, arrhythmias, headaches, asthma, and
digestive problems. The condition affects people from all walks of life,
including hairdressers, pesticide applicators, homemakers, chemical plant
workers, office workers, and Gulf War veterans.
SO FAR, there is no generally effective way to treat chemical
intolerance, except by avoidance of the chemicals, foods, and other substances
that trigger symptoms. But sometimes it is impossible to identify the precise
substances. To regain their health, some severely affected patients totally
disrupt their lives, such as moving to a house with few sources of toxicants
in a rural area where exposures to factory emissions and traffic exhaust are
A phenomenon called masking makes it difficult for the chemically intolerant
to know what is triggering their symptoms, Miller said. If people are
sensitive to a variety of substances, they can go through the day reacting to
fragrances, hair spray, vehicle exhaust, foods, and other substances that
create a confusing array of symptoms. The response to each substance overlaps
with the next, and the effect of any single exposure is not apparent.
A decade ago, many physicians claimed chemical intolerance did not exist--that
patients who believed they suffered from low-level chemical exposures have a
psychosomatic illness. Now, there is widespread recognition that the vast
majority of these patients are indeed sick and that their symptoms have
something to do with chemical exposures.
"Most people seem to have a natural ability to tolerate a wide variety of
exposures," both natural and synthetic, Miller said. The chemically
intolerant have lost that natural resistance.
"From a toxicologist's point of view, this sort of response to
structurally unrelated substances is difficult to understand or believe,"
Miller continued. "The exposure levels that cause symptoms are orders of
magnitude below established safety limits. We may be dealing with a new
paradigm for environmentally induced illness--in fact, perhaps, an entirely
new disease mechanism."
THE SPEAKERS at the meeting presented studies that illustrate how some
of the research methods employed in addiction studies might be used to study
chemical intolerance. They also discussed research that shows similarities
between addiction and chemical intolerance.
E. McKeown-Eyssen, a professor in the department of public health sciences
and nutritional sciences at the University of Toronto, matched 203 chemically
intolerant women with 162 women as controls. Blood samples from patients and
controls were analyzed for variants of six genes. She found significant
variations, called polymorphisms, of three genes--CYP2D6 (cytochrome P4502D6),
NAT2, and PON1--in the intolerant cases compared with the controls. All of
these genes are involved with metabolism of environmental contaminants, she
One explanation of these findings might be that the chemically intolerant
metabolize environmental chemicals differently than do healthy individuals,
McKeown-Eyssen said. Some specific enzymes--gene products of these
polymorphisms--are likely associated with chemical detoxification, she said.
For example, CYP2D6 is key to the metabolism of a wide variety of diverse
substances, including therapeutic drugs, drugs of abuse, and neurotoxins. The
arylamine transferases expressed by NAT2 metabolize aromatic amines, as well
as other substances, and PON1 is essential for the metabolism of
organophosphate pesticides, which several researchers have implicated in the
initiation of chemical intolerance. Individuals with selected polymorphisms of
both CYP2D6 and NAT2 were 18 times as likely to be among the chemically
intolerant, suggesting that gene-gene interactions need to be considered, she
said. But before firm conclusions can be drawn, "the study needs to be
replicated because the numbers of cases and controls with some genotypes were
quite small," she said.
NIAAA Director Ting-Kai Li described genetic differences in humans that make
some people susceptible to excessive drinking of alcoholic beverages and lead
others to avoid alcohol. He also discussed his work with rodents that shows
marked differences in voluntary alcohol consumption and explained how the
knowledge and techniques used to study alcoholism might be applied to chemical
In the U.S., 8.5% of the adult population suffers from alcohol abuse or
dependence, Li said. There is about a three- to fourfold difference in
individual responses to alcohol, and about half of this is genetic, he said.
Genetic predisposition to drink, he explained, depends to a large extent on
variants of the alcohol dehydrogenase gene (ALDH2) and the aldehyde
dehydrogenase gene (ADH).
When alcohol is consumed, it is first converted to acetaldehyde by the alcohol
dehydrogenase enzyme and then to acetate by the aldehyde dehydrogenase enzyme,
Li said. Ethanol is both a stimulant and a depressant; acetaldehyde is a
stimulant and also a toxic compound that causes aversive reactions. Acetate is
a depressant. Those who have genetic variants of the ADH gene that make it
difficult to metabolize acetaldehyde generally find drinking unpleasant
because they can't eliminate the toxic acetaldehyde, he explained. Drugs, such
as Antabuse, developed to treat alcoholism, prevent the conversion of
acetaldehyde to acetate. As a consequence, the drugs cause a highly unpleasant
reaction when alcohol is ingested.
Because nearly all people with chemical intolerance feel sick when they
consume even small amounts of alcohol, research on the biological mechanisms
of alcohol in these patients might help elucidate why it causes such extreme
reactions, Li said. Certain Gulf War veterans, who in the past could tolerate
a great deal of alcohol, find that they can't drink even one beer after they
become chemically intolerant.
"Another parallel is there are a variety of acetaldehydes and other
aldehydes in the environment," Li said. They are in tobacco smoke, some
foods, and traffic exhaust. The chemically intolerant may not be able to
metabolize these aldehydes, just as they can't deal with the acetaldehyde
metabolized from alcohol, he explained.
R. Griffiths of the Johns Hopkins University School of Medicine discussed
caffeine addiction and its relevance to chemical intolerance. "Caffeine
is the most widely used mood-altering drug in the world," he said. In the
U.S., 80-90% of adults are regular consumers, with a mean daily intake of 280
mg, mostly from coffee and soft drinks. A 6-oz cup of coffee has an average of
100 mg of caffeine, while a caffeinated 12-oz soft drink has about 40 mg.
"Chemically intolerant people have unusual sensitivity to low doses of
caffeine and are more likely than those in the general population to be either
addicted to or avoidant of caffeine," Griffiths said.
In most people, low doses of caffeine have primarily positive effects,
producing a sense of well-being, increased energy, alertness, self-confidence,
and decreased sleepiness, he said. "On the other hand, higher doses of
200-500 mg may produce anxiety, nervousness, and jitteriness."
"In prospective experimental studies, 13% of caffeine consumers had some
kind of functional impairment, such as missing work or failing to complete
daily responsibilities, if they went through caffeine withdrawal,"
Griffiths reported. "Avoidance of withdrawal symptoms plays a central
role in the habitual consumption of caffeine."
Some people are able to detect doses of caffeine as low as 1.8 mg, and such
low levels are physiologically active in those individuals, Griffiths
observed. "Just as low doses of chemicals trigger negative reactions in
the chemically intolerant, caffeine-susceptible individuals experience
withdrawal symptoms after consuming surprisingly low amounts of caffeine for
only a few days."
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