Intolerance, Susceptibility, Hypersensitivity

Intolerance, susceptibility and hypersensitivity

Medical staff in France and other countries are increasingly becoming aware of the occurrence of new pathological disorders or diseases caused by environmental exposures as a consequence of human activity. In addition to the enormous increase in incidence of food allergy and intolerance, entirely new pathological disorders or diseases have emerged over the last thirty years.

    1. Towards a new characterization of the toxicological mechanisms involved in electro-magnetic and/or chemical intolerance and hypersensitivity

    We define intolerance to EMF as a clinico-biologic entity that we termed EMF intolerance syndrome or EMFIS. As previously indicated, intolerance to EMFs is unfortunately often confused with Electro-hypersensitivity (EHS). Similarly, "idiopathic environmental intolerance" such as reported by the WHO should be clinically and biologically distinguished from the clinico-biologic entity termed " multiple chemical sensitivity ", that physicians in France call improperly " odor intolerance syndrome." Until recently, intolerance and/or hypersensitivity to chemicals were mostly confined to the health effects induced by inhalation, ingestion or dermal application of natural chemicals; and those considered to involve immuno-allergic mechanisms.

    For example, asthma and atopic rhinitis were considered to be diseases of purely allergic origin, simply reaction to allergens. Food intolerance also was called "allergy” due to ingestion of allergens present in food and the production of digestive and systemic side effects. More rigorous thinking with evidence-based environmental medicine indicates that:

    * many marketed products containing artificial chemicals – often unfamiliar to evolved life – have been proved to be involved in the genesis of many current pathological disorders and diseases;

    * purely electric or electromagnetic non-ionizing radiation, whatever their wavelength, can cause EMFIS.

    The fact that radiation as well as chemicals can induce similar health effects in patients, as evidenced by the possibility of genesis of intolerance and/or hypersensitivity syndromes drastically modifies our scientific understanding of the mechanisms that may be involved. Minimizing the hypothesis of a simple immuno-allergic phenomenon (always possible in some cases, but much more infrequent than previously thought); we instead came to recognize that inflammation (the activation of the immune system to foreign agents) is the initial outcome, whether it is caused by chemical or radiation agents. We particularly outlined the pathologic effects of "low grade " chronic inflammation resulting from the prolonged low-dose exposure to these agents. This new source of inflammation can thus be distinguished from the inflammation caused by allergic phenomena, which life has evolved and and which may not be as constant an exposure.

    In addition, we came to recognize that the indirect health effects of inflammation often spread from the original site of exposure not only to peripheral organs such as the heart and the blood vessels, the bronchus and the lungs, the skin and the intestinal mucosa, but mainly to the nervous system. It is noteworthy that inflammation and consequently the health effects caused by these diverse chemical or radiation agents mainly involves the central nervous system, especially the brain. Aside from the above reported indirect effects, a common (inhaled ingested or dermal) direct exposure path of external agents is through trans-cranial and transnasal routes respectively for radiation and some chemicals; bypassing the blood-brain barrier.

    Indirect effects via the blood to respiratory or digestive systems (for chemicals), as some chemicals that cross the blood-brain barrier; a barrier that in normal conditions protects brain cells from the toxic substances in the blood.

    It is well known indeed that some volatile chemicals inhaled nasally can pass through the nasal mucosa roots of the olfactory nerve, then the nerve itself, the bulb of the nerve and finally in the rhinencephalon, a phylogenetic-old brain organ located in the inner part of the temporal lobes; often creating a neuro-inflammation along this path.

    Thus we should consider the existence of two types of mechanisms of crossing over of the blood-brain barrier leading to cerebral neuro-inflammation: a natural one associated with the nasal path to the brain for inhaled chemicals; and an artificial one, associated with a direct trans-cranial effect of EMFs on this barrier, or of chemicals present in the bloodstream that penetrate blood vessels and cross over the blood-brain barrier.

    In addition, because of a possible inflammation of the intestinal barrier due to the presence of chemical residues in food or even to a direct target effect of EMF on the intestine, the intestinal barrier may become permeable, thus enabling food-associated toxic chemicals to pass it and enter the blood stream to potentially affect the nervous system (inter alia). In addition, of course, toxic agents may be absorbed due to foods and microflora present in the gut.

    Altogether, under the influence of various environmental factors, opening of the intestinal barrier and the blood-brain barrier may be causally linked, due not only to direct toxicological factors (solubility, volatility, refractionness, etc.), but also to indirect patho-physiological side effects the effects on one barrier affecting the other and vice versa. This may explain why chemical and/or EMF intolerances are often associated with food intolerance and why when this is clinically established, the phenomenon of intolerance and hyper-sensitivity to EMFs and/or to chemicals may be amplified.

    But the problem is even more complex, because in addition to food chemical residues that cause inflammation thus increased intestinal permeability and consequently food intolerance, intestinal flora dysfunction may in fact be involved as well. Indeed, under the potential effect of a possible diet imbalance or even of a toxic effect of chemical residues on the intestinal flora bacteria, the resulting dysbiosis may itself contribute to increased intestinal permeability and to food intolerance; and consequently to the entering of toxic chemical residues into the blood stream and to an opening of the blood-brain barrier.

    Checking food intolerance in patients with intolerance to EMFs and/or to chemicals is therefore necessary for implementing an adequate patho-physiologically-based treatment.

    However in association with a possible food intolerance we should consider the three nosological entities we have previously delineated: intolerance, susceptibility and hypersensitivity which are certainly closely dependent on each other, but fundamentally different as far as the clinical aspects and the toxico-biologic mechanisms are concerned.

      2. Intolerance

      Intolerance is defined as the occurrence of clinical symptoms and biological abnormalities when a subject is transiently or continuously exposed to electric fields (EFs) or electromagnetic (EMFs), or to artificial chemicals. Initial symptoms may be acute or sub-acute. In the case of prolonged exposure, they may however arise clinically in a chronic, progressively increasing way. The hallmarks that characterize intolerance is its occurrence for high intensities of EFs or EMFs, or for elevated concentrations of chemicals--in other words for intensities or concentrations that are not necessarily low. In addition it should be noted that initially symptoms of EMF intolerance usually occur for "certain" wavelengths (extremely high or low frequency RFs or microwaves); while symptoms for chemical intolerance occur for one or a limited number" of chemicals (pesticides, organic solvents, perfumes, exhaust gas from cars, household goods, etc…). Moreover we should consider that intolerance isn’t necessarily associated with susceptibility nor with hypersensitivity to these agents, meaning that there is no individual cause, whether innate or acquired that may be necessarily associated to cause such intolerance condition. In other words anyone, regardless of his genetic and/or epigenetic constitution, may become intolerant and thus be subject to further pathological disorders or diseases caused by these agents, at any exposure level or duration.

        3. Susceptibility

        Susceptibility is defined by the fact that all subjects facing to EMFs or chemicals do not react in the same way. While a number of people seem to tolerate electromagnetic and chemical pollutants yet at the today intensities and doses, others do not. However this will not probably be the case tomorrow for a majority of people because of the increased duration of exposure to these agents, the increasing number of sources (EMFs) and the increasing number of products (chemicals) on the market. In an ARTAC survey on EMF and/or chemical intolerance, all professions appear to be concerned, but more especially those for which there is a prolonged EMF exposition (computer, air traffic controllers, telephone operators, PAO users, sale persons) and/or chemical exposition (workers of the chemical industry, workers in laboratories using chemical reagents, construction workers, etc...).

        Women are far more susceptible to both EHS and MCS, as 2 out of 3 such patients are women.

        In addition to the role of gender, a hereditary genetic polymorphism including the influence of individual susceptibility genes is most likely involved. Several such susceptibility genes have been evidenced in MCS. ARTAC is studying the possibility of similar genes among members of EHS families, in the framework of an international research collaboration. In addition to genetic hereditary susceptibility factors, epigenetic acquired (environment-related) factors may play of course a key favoring role, such as in the case of cancer.

        ECERI organized an international workshop on epigenetics applied to cancer in November 2012 in Brussels, in partnership with the Royal Belgium Academy of Medicine and in the presence of a scientific researcher from IARC, the International Agency for Research on Cancer. Evidence shows: (1) the presence in cells of a very complex structured molecular network linking extracellular environment to the DNA according to dynamic and functional mechanisms, and therefore ensuring the functioning of every cell in contact with its environment; (2) the epigenetic concept of epimutations ie environment-induced extra DNA molecular structure modifications being a mirror of the genetic concept of DNA mutations, (3) the regulation of gene expression thanks to the epigenetic network; (4) vice versa the synthesis of molecules of the network by structural genes; (5) the constitution of an " epigenetic memory " enabling the transmission of a so-called environmental signature through  (3) or (4) further cell generations; and finally (6) the possibility of an inherited familial transmission of this memory.

        Thus in addition to the classic genetic, innate and constitutional heredity, it is now appropriate to add an environmental epigenetic acquired inheritance. Epigenetics helps to understand the footprint of the environmental in cells and organs, especially in the case of chronic exposures to toxic agents. What is now accepted for cancer at the standpoint of epigenetics might also apply to the intolerance to the syndromes involving EMFs and/or chemicals, and therefore to the hypersensitivity that may result in susceptible patients. In other words, that hypersensitivity may not occur only in constitutionally susceptible people due to genetic polymorphism, but also in not necessarily genetically susceptible people, as a consequence of epigenetic alterations acquired in contact with the environment, is highly possible. So in terms of intolerance and a fortiori of hypersensitivity to EMF, the occurrence of an electrocution (acute intolerance) or the presence of metallic prosthesis acting as antenna (chronic intolerance), such as wire-rimmed glasses, metal dental amalgams (particularly mercury), gold jewelry, pacemakers, orthopedic implants etc. should be considered. Likewise in the case of intolerance (and hypersensitivity) to chemicals, the causal role of an acute, sub-acute or chronic exposure to some synthetic chemicals should be considered as well as the occurrence of possible synergistic / potentialization effects.

          4. Hypersensitivity

          Hypersensitivity is a full-spectrum clinical and biological phenomena. It is possibly related to the susceptibility phenomena that we have previously described, i.e. it may preferably occur in genetically and/or epigenetically susceptible people. What we know is that it can be generated by either intense or low but generally prolonged exposure. Hypersensitivity, although its patho-physiological mechanisms are still unclear, has clearly to be distinguished from intolerance and susceptibility, as discussed above. There are actually two types of hypersensitivity to consider, although their patho-physiological mechanisms may be similar: electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS).

            4.1 Electrohypersensitivity (EHS)
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            EHS is defined (1) first and foremost by the lowering of the clinico-biological tolerance threshold of the body to electromagnetic fields, i.e. by the occurrence of intolerance at low or very low EMF intensity, possibly even at the limit of the detection threshold by the most sensitive measurement equipment; and (2) by the progressive extension of intolerance to other or all frequencies of the electromagnetic spectrum (extremely low, low, radio, and high frequencies). Sensitivity can develop to such a point that some patients with very advanced hypersensitivity may become intolerant to ultraviolet rays and even to visible light, whether natural or artificial. Thus in the case of such an extreme photosensitivity, as we have observed in the ARTAC series of so-called EHS patients, several of them must wear permanently a patch on the eyes or may even become blind.

            Note that in the current electrosmog environment, at the beginning of EHS most often radio-frequencies are responsible, before it gradually extends to high and very high frequencies, and sometimes to low and extremely low frequencies. Less frequently in some cases intolerance first starts to low or extremely low frequencies before gradually extending to the whole spectrum. Thus electro-hypersensitivity must be regarded as a serious problem in terms of public health, because patients with EHS may actually represent the most visible part of much broader damage caused by EMFs, i.e. as previously indicated, "the tip of the iceberg," a phenomenon that has to be linked to the current proliferation of electromagnetic sources (electrosmog) and increased exposures to these sources.

            This clearly means that, without necessarily presenting an EHS syndrome, many patients may today consult medical practitioners for intolerance symptoms related to EMFs, such as migraines, cardiac dysfunction dermatitis, degenerative neuropathies, chronic rheumatisms, autoimmune diseases, chronic fatigue, and even cancers, etc. ... while the causal link between EMF exposure and these various pathologies have not yet been identified.

            As indicated above, the current diagnosis of EHS patients reveals a much more serious public health problem, yet is largely unsuspected by the medical community, health professionals and public authorities.

            What could be the patho-physiological mechanisms of electrohypersensitivity? As with bacteria, bees and birds, humans are all normally electro-sensitive due to the presence of magnetosomes in some cells, especially those of the nervous system. Given the clinico-biologic experience and current ARTAC research, what may differentiate EHS patients from intolerant people is the acquisition of a particular biological footprint, thus amplifying the natural electrosensitivity, in a hardly reversible way. Thus, some of the people intolerant to EMFs may develop, depending on their innate (genetic) or acquired (epigenetic) susceptibility a particular state, comparable to what is known as atopy in allergic patients, but which clearly differs biologically from it, what we call "hypersensitivity". It is therefore clear that the acquisition of an hypersensitivity condition doesn’t resolve all the health threats, since one can be intolerant to EMFs without being electrohypersensitive. Finally while current treatments along with the withdrawal of electro-magnetic sources can quite often help overcome the clinico-biologic symptoms of intolerance; by the present state of knowledge they do not cure hypersensitivity except in some very rare cases.

              4.2. Multiple chemical sensitivity (MCS)
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              As with EHS, sensitivity to multiple chemicals (MCS) is a chronic disorder caused by a biological phenomenon which is still not understood. MCS is a syndrome defined by the same types of criteria as for electro-hypersensitivity: patients become progressively intolerant to weak or even extremely weak concentrations of chemicals. In addition, while initially intolerant to one chemical or to a very small number of chemicals, MCS patients gradually become intolerant to multiple chemicals; sometimes so many as the patients are entirely incapacitated. All classes of chemicals may be involved, but especially synthetic marketed chemicals, such as oil paintings, organic solvents, perfumes, cosmetics, cleaning products (washing powders and especially chlorine bleach), factory fresh inks; also pollutants such as car exhaust gases, tobacco smoke, pesticides or heavy metals etc. These may be responsible for intolerance and hypersensitivity genesis.

              A major point is that MCS most often results from an initial acute or sub-acute intoxication, by one or several chemicals (sometimes occupationally) and that because of this initial event, MCS gradually develops. We must stress that the two health events are indeed causally related.

              Despite MCS recognition by WHO, medical ignorance still causes MCS patients to cope with severe medical and social consequences without any acknowledgement of their pathological condition (i.e. or of its origin in an acute or sub-acute exposure event), and therefore are not recognized medically and socially and so are not treated adequately nor taken in charge correctly by the public health and social security systems.

              A second important point issued from the ARTAC research is that over time patients with MCS can develop hypersensitivity to EMFs and vice-versa, patients with EHS can develop true MCS, a finding suggesting that as already outlined EHS and MCS may originate through common physio-pathological mechanisms.

              A third point is that contamination by certain heavy metals (mostly mercury, nickel, gold, silver, copper, titanium, etc...) sometimes part of dental amalgams, may contribute not only to MCS but also can contribute to the development of hypersensitivity to EMFs, as shown by clinical improvement of EHS observed following removal of amalgams. But this occurs only if removal is performed using a specific precautionary procedure.

              In sum, according to the results obtained from the ARTAC series of patients, we concluded that occurrence of MCS can be primary or secondary to EHS or vice-versa EHS can occur primarily or secondarily to that of MCS. These two clinico-biological entities seem to be causally related and perhaps constitute a unique patho-physiologic entity.

              A fourth point from the ARTAC study is that MCS and EHS may be significantly associated with food intolerance, in particular to gluten, and/or to lactose and casein, which are often associated with an inflammation of the intestinal mucosa, although the precise mechanism remains unclear.

              Such a food intolerance can lead to an extremely severe disease characterized by gastrointestinal symptoms and possibly considerable weight loss . In order to prevent such evolution, a diet without gluten, lactose and caseins and eventually other nutrients  is proposed. Moreover food intolerance requires prescribing of drugs free from excipients. Because MCS and EHS may appear in food intolerant patients, we suggest that all three entities are closely linked, even if the precise unifying mechanism remains unknown. These hypersensitivity syndromes demand appropriate medical recognition, adequate treatment and also prevention i.e. avoidance of electromagnetic fields, chemicals and certain nutrients.

                4.3. Is hypersensitivity reversible?
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                In the present state of knowledge, once chemical and / or electromagnetic hypersensitivity appear, they cannot be reversed, despite the use of currently available treatments and usual preventive methods. However, as soon as the first symptom of intolerance occurs, if drastic measures aiming at avoiding the causative agents are taken, treatments may in addition effectively limit the development of hypersensitivity, and even stop it in some cases. Indeed, we know that the expression of susceptibility genes irreversibly influences the response of the organism to environmental change. Crucially, this is not the case for epigenetic alterations, which a priori can be reversible after withdrawal or alteration of the environmental cause(s). To the extent this is true, the chances of regression are greater still. Of course it is necessary for the treatment and avoidance measures to start before the establishment of irreversible anatomic lesions associated with neuro-inflammation. We therefore might expect sometimes a significant degree of hypersensitivity reversibility. This in particular is the research that ARTAC in France and ECERI in Europe are engaged in.

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