Allergy and Hypersensitivity – Looking Through the Oxygen Prism

Majid Ali, M.D.

I. Introduction

II. Looking Through the Oxygen Prism

III. The Classical Atopic Perspective

IV. The Ecologic Perspective

V. Particulate Matter, Pollutants, and


VI. Oxidative Regression to Primordial Cellular Ecology

VII. Pathogenesis of Chemical Sensitivity: Oxidative-Dysoxygenative Dysautonomia?

VIII. Mold Desensitization and Antifungal Therapies

IX. The Enterohepatic Therapies for Preventing Food Reactions

X. Oxystatic Therapies

XI. Healing in Chemical Sensitvity: A Case History

XII. Concluding Comments


In my clinical experience, daily administration of oxygen by mask with hydrogen peroxide foot soaks often reduces the frequency and intensity of hypersensitivity reactions. What may be the mechanism of action in this context? I have also commonly observed that therapeutic measures directed at ‘bowel cleansing’ and ‘liver detox’ reduce the frequency and intensity of hypersensitivity reactions—or eliminate them altogether under certain circumstances. What might be the operant mechanisms there? Why do some antigens trigger hypersensitivity responses at some time but not others in the same atopic individual? Why does the same antigen evoke strong responses under one set of conditions but very weak reactions under another? For the same individual, why does antigen immunotherapy provide near-complete relief of allergy symptoms at some time but not others? Why does the spectrum of symptom-complex induced by antigenic stimuli vary over a broad range? None of those questions can be answered with the established knowledge of the Gell and Coombs or any other recognized types of hypersensitivity reactions.

Eczema lesions in the same person flare more during some weeks than in others. In the same asthma sufferer, lifestyle stressors exaggerate bronchospasm more on some days than on others. Symptoms of Crohn’s colitis and ulcerative colitis remit and relapse for no apparent reason in most instances. Food sensitivity reactions vary over a broad range in the same individual. Allergic rhinitis becomes more intense on some days when pollen counts are low and abates on days when pollen counts are high. The phenomenon of “spreading sensitivity reactions” (long vigorously denied by IgE researchers) is increasingly recognized in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity syndrome. The molecular explanation of none of the above can be understood on the basis of the known immunologic responses.

The oxidizing capacity of Earth is steadily increasing, and so is the cumulative burden of particulate matter and other pollutants in the ambient air. How do those changes affect the physiological and pathological inflammatory responses that is integral to all immunologic hypersensitivity reactions? In this column, looking through the prism of oxygen homeostasis, I explore those questions and offer some explanations. In my view, some aspects of pathophysiology of oxygen homeostasis and redox equilibrium are not only crucial in understanding the wide range of clinically recognized hypersensitivity responses, but also for formulating a rational and scientifically sound integrative management plan for hypersensitivity disorders.



In 1993, with the writing of Spontaneity of Oxidation and Aging,1 I began my clinical, biochemical, and pathologic studies with the central purpose of looking at the health/dis-ease/disease continuum through the prism of oxygen homeostasis. In 1998, in an article entitled “Oxidative Regression to Primordial Cellular Ecology (ORPEC),”2 I presented a large body of data to support my hypothesis that progressive and unrelenting oxidative stress eventually creates cellular conditions that simulate primordial, predominantly glycolytic metabolism. Later, in an article entitled “Darwin, Oxidosis, Dysoxygenosis, and Integration,” I extended the ORPEC concept by focusing on impaired mitochondrial function and respiratory-to-fermentative shift in ATP production in patients with persistent energy states, including fibromyalgia, chronic fatigue syndrome, and chronic fatigue following chemotherapy for cancer.3

In 2000, I presented the oxidative-dysoxygenative (OD) model of IgE-mediated allergy in Current Opinion in Otolaryngology.4 The OD model of atopy is a unifying model that integrates diverse clinical, biochemical, morphologic, and experimental observations in the following three areas: (1) classical studies of IgE-mediated atopic response and, to a lesser degree, the other three types of Gell and Coombs hypersensitivity responses; (2) an ecologic view of clinical allergy that includes sensitivity to environmental agents independent of the dose of the excitant; (3) an expanded, integrative perspective of hypersensitivity responses that focuses on oxidative-dysoxygenative dysfunction (OD), which profoundly influences sensitivity reactions included in the first two categories. In 2000, I also proposed that oxidative coagulopathy is a major pathogenetic mechanism of hypersensitivity disorders in an article published in Environmental Management and Health.5 My focus there was on oxidative-dysoxygenative phenomena in the circulating blood that provide an important mechanism for turning local chemical sensitivity responses into the complex and yet well-characterized systemic symptom complexes.

Human external and internal ecosystems are under increasing oxidative stress. The oxidizing capacity of the planet Earth is increasing.6 The ozone layer is thinning and is oxidizing.7 Global anoxia is increasing and is oxidizing. 8 Ever-increasing levels of fossil fuel burning is increasing oxidant stress. Industrial pollution is increasing, and most pollutants are oxidizing. The greenhouse effect is oxidizing. Ten thousand years ago the estimated average temperature of Earth was 50 degrees F,9 and it has been steadily rising. From January to July 1998, average temperatures consistently broke previous monthly records, with temperatures rising to 124 degrees F in India, claiming 3,000 deaths.10 The total oxidizing burden of the above natural and anthropogenic elements on human ecosystems has increased enormously in recent decades.

As for the various body organ ecosystems in environmental medicine, oxygen transport and utilization in chemical sensitivity is impaired, as evidenced by increased urinary excretion of toxic organic acids (such as tartaric acid) that inhibit the Krebs cycle.11 Clinical evidence for that is furnished by the pervasive sense of “air hunger” among patients with environmental illness and clinical benefits of oxygenative therapies for such patients.12 The bowel ecology disrupted by massive sugar overload and extended antibiotic use (which feeds yeast and primordial flora) is oxidizing.13 Lactic acidosis and dehydration, almost invariably seen in advanced environmental illness, is oxidizing by interfering with the Krebs cycle as well as hepatic enzyme detoxification pathways. This subject has been recently discussed at length. 14

The integrative oxidative-dysoxygenative model has a strong explanatory power for many hitherto poorly understood aspects of clinical allergy. Beyond that, this model provides a scientifically sound basis for adding specific antigen immunotherapy to nutritional, antioxidant, detoxification, and oxygenative therapies to enhance clinical benefits. To provide a historical frame of reference for presenting this subject, I include below some brief comments about the classical atopic and clinical ecology perspectives.


In 1902, Charles Robert Richet ushered in the age of experimental study of hypersensitivity phenomena with his description of anaphylactic reaction.15 Four years later, Von Pirquet introduced the term allergy (derived from the Greek words allos [other] and ergia [energy]) for an altered state of immune responsiveness or “changed reactivity” of an individual.16 In 1911, Noon introduced specific antigen immunotherapy.17 In 1923, Coca and Cooke proposed the term atopy (derived from the Greek word atopos, meaning strange or uncommon) for an abnormal state of hypersensitivity in an individual, rather than a hypersensitive response in a healthy individual, and believed that such sensitivity could not be transferred to animals or humans.18 In 1921, Prausnitz and Kustner laid the cornerstone for immunologic investigation of allergic phenomena in humans by documenting the presence of a transferrable skin-sensitizing factor in the serum of allergic individuals.19 In 1964, Gell and Coombs proposed their classification of four mechanisms of allergic reactions, Type-I reaction being the response mediated by the reaginic antibody.20 In the mid-1960s, Ishizaka established the IgE as a new unique immunoglobulin on the basis of the following three principal criteria: its ability to bind the specific antigen, its unique antigenic determinants, and its correlation with biologic activity, as demonstrated by the P-K technique.21 In 1966, Wide et al.22 described the radioallergosorbent test (RAST) for semi-quantitative measurement of allergen-specific IgE antibodies, and ushered in the era of in vitro diagnosis of allergy. In 1979, my colleagues and I demonstrated local IgE production in plasma cells in nasal mucosa of atopic persons23 and in nasal polyps.24 The same year, my colleague, Madhava Ramanarayanan, and I described micro-ELISA assays for allergen-specific IgE and IgG antibodies and, to achieve a higher level of assay sensitivity and specificity, developed a methodology for accounting for a range of variability in the nonspecific binding among individual antigens.25,26 Employing that assay, Hurst and colleagues demonstrated the local production of allergen-specific IgE antibodies in the middle ear mucosa and firmly established such mucosa as the primary target of the atopic response.27


The discipline of clinical ecology evolved to focus on clinically verifiable patterns of hypersensitivity reactions that could not be explained on the basis of any of the Gell and Coombs immunologic sensitivity mechanisms. Clinical ecology was defined as the study of the effects of the environment upon the individual by the pioneers of the field, including Randolph,28 Rea,29 Waickman,30 and others. Chemical sensitivity was defined as an adverse response of an individual to environmental chemicals at levels that are generally considered safe. Thus, chemical sensitivity is independent of the dose of excitant. The core concept of chemical sensitivity holds that clinical expression of an adverse reaction is determined by the following: (1) the body tissue or organ involved; (2) the chemical nature of the excitant trigger; (3) the biochemical individuality of the person (the individual susceptibility of the person to a given excitant); (4) the length of the exposure; and (5) the existence of concurrent but unrelated stressors as well as synergism among them (the concept of total load). Four general principles that govern the cause-and-effect relationships in clinical ecology are: (1) total load; (2) adaptation (first described by Selye31 and including masking or acute toxicologic tolerance); (3) bipolarity (consisting of an initial stimulatory phase followed by a depressive phase); and (4) biochemical individuality.

The core tenets of clinical ecology represent crucially important conceptual advances beyond the classical atopy because they explain a broad spectrum of clinical manifestations not accounted for by the latter. The IgE researchers continued to focus on issues of single-allergen sensitivity and consequences of specific immunotherapy in such disorders. The ecologists, while recognizing the theoretical merit of such work, found those findings to be of very limited clinical value, since allergic persons invariably suffer from multiple sensitivities. After decades of doubt and denial,32 the existence of multiple chemical sensitivity syndrome was finally acknowledged and its relevance to the management of the classical allergy understood.33

Altered States of Bowel Ecology

During the 1970s and early 1980s, many pathologic, biochemical, and clinical observations convinced me of the need to look at the bowel as an ecologic system. (See for nearly thirty of my articles on the subject). That academic interest also led me to investigate the role of altered states of the bowel ecosystem on the clinical manifestations of hypersensitivity reactions. For example, a marked improvement in symptoms of atopic dermatitis was observed in many patients with empirical therapies that putatively “restored the bowel health.” Relief of constipation was associated with relief of sinusitis headache in others. Symptoms of allergic rhinitis often subsided with antifungal therapies. All those considerations allowed me to introduce the concept of altered states of bowel ecology as the basis for heightened hypersensitivity states.


Particulate matter (PM) in ambient air inflicts oxidative injury and induces inflammation in microecologic cellular and organ-system macroecologic systems. Such injury involves myriad prooxidant and proinflammatory pathways, as well as antioxidant and antiinflammatory systems.34-37 Examples of the former include cellular heme oxygenase-1 (HO-1), NADPH cytochrome P-450 reductase (P-450 reductase), nitric synthase, sulfates, nitrates, organic hydrocarbons, metallic compounds, and prooxidant transition metals, such as copper, vanadium, chromium, nickel, cobalt, and iron. The counteractive antioxidant/antiinflammatory responses evoked include superoxide dismutase, catalase, glutathione peroxidase, and antioxidants.

Those changes have been closely examined in the pulmonary and cardiovascular systems and other microecologic cellular and tissue-organ macroecologic systems. The uptake of PM in macrophages and epithelial cells and induction of oxidative stress is affected by differences in the size—coarse particles (2.5-10 microns), fine particles (< 2.5 microns), and ultrafine particles (UFP, < 0.1 micron)—and composition of such matter. UFPs are the most potent inducer of cellular heme oxygenase-1 (HO-1) expression and depletion of intracellular glutathione. Furthermore, HO-1 expression is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs.34 What increases the biological potency to UFPs markedly is their localization in mitochondria.35

Diesel exhaust particles (DEP) in ambient air contain redox cycling organic chemicals with potent prooxidative and proinflammatory responses. Such effects are associated with a documented increase in the production of over thirty proteins—a number that will definitely increase with time. Technologies in current use for such studies include matrix-assisted laser desorption/ ionization-time of flight mass spectrometry and electrospray ionization liquid chromatography-mass spectrometry. In doses ranging from 10-100 ìg/ml, organic DEP extracts induce incremental impairment of cellular glutathione systems—a decline in glutathione/oxidized glutathione (GSH/GSSG) ratio, in parallel with a linear increase in newly expressed proteins. Other antioxidant enzymes and proteins produced in response to DEP (in addition to the above-mentioned heme oxygenase-1) are catalase, proinflammatory components (p38MAPK and Rel A), and products of intermediary metabolism regulated by oxidative stress. At DEP extract doses of over 50 ìg/ml, a steep decline in cellular viability has been documented.36

The biologic effects of PM and DEP are inhibited by a variety of antioxidants and antioxidant enzyme systems, including N-acetylcysteine (NAC), superoxide dismutase (SOD), and others, by a variety of mechanisms.35,36 For instance, N-acetylcysteine (NAC), which directly complexes to electrophilic DEP chemicals, suppresses DEP-induced effects. Not unexpectedly, such responses to pollutants also evoke responses from certain oxidant-generating enzymes, such as NADPH cytochrome P-450 reductase (P-450 reductase), which has been detected mainly in ciliated cells in the respiratory passages. By contrast, CuZn-SOD and Mn-SOD have also been found in the airway epithelium. Another important system induced by DEP is constitutive NO synthase (cNOS) in the airway epithelium and inducible NO synthase (iNOS) in the macrophages. Pretreatment with NG-monomethyl-L-arginine, a nonspecific inhibitor of NO synthase, significantly decreases DEP-induced bronchial hyper-responsiveness.

The increasing amounts of minerals generally increase the degree of oxidative stress in biologic systems. This issue has also been examined in the case of PM- and DEP-induced responses. For instance, the degree of chemiluminescence—an indicator of oxidative stress—shows a strong association between such stress and the amounts of iron, manganese, copper, and zinc in the lung and with iron, aluminum, silicon, and titanium in the heart.37

In a recent issue, Science reported that particulate matter is estimated to kill more than 500,000 people each year.38 What can be made of that number when one realizes that one of every four children in New York City carries an inhaler to school? PM comprises solid and liquid particles derived from industrial and vehicular exhaust, smokestacks, forest fires, windblown soil, road dust, volcanic emissions, and sea spray39-41 Ultrafine particulates are largely derived from combustion of fossil fuel and have a core of elemental carbon coated with layers of chemicals, such as sulfates, nitrates, organic hydrocarbons, and metallic compounds.42

The prooxidative/proinflammatory effects of many components of PM are well established. Organic hydrocarbons, including polycyclic aromatic hydrocarbons, quinones, and transition metals (copper, vanadium, chromium, nickel, cobalt, and iron) also play a role.43,44 PM serves as a template for electron transfer to molecular oxygen in redox cycling events involved in the above.45 Additional oxyradicals are also produced in target cells (bronchial epithelial cells, macrophages, and others) when contacted by PM. Of special interest in this context are oxyradicals produced in response to particle uptake by biologically catalyzed redox reactions in the matrix, biomembranes, and mitochondria.46-48 The oxyradical-inflicted damage includes that affecting: (1) cellular proteins (especially those involved in intracellular signaling cascades); (2) lipids; (3) complex sugars; (4) DNA; (5) molecular species of epigenetic regulatory mechanisms; (6) cytokines and transcription factors, such as NFk-B49 and eventually cytokine and chemokine genes.44,45,50-52 These products are produced locally in target tissues as well as systemically and lead to widespread proinflammatory effects remote from site of damage.


In an earlier column, I briefly described the phenomenon of oxidative regression to primordial cellular ecology (ORPEC).2 Briefly, it is a dysox state in which persistent oxidosis, acidosis, and dysoxygenosis create cellular metabolic conditions that closely simulate those existing in the primordial era, before there were biologically significant amounts of oxygen in the ambient era. The ORPEC state is associated with overgrowth of anaerobic species in the bowel, blood, and other tissue.

In my clinical experience, indolent hypersensitivity states—those caused by any of the Gell and Coombs hypersensitivity responses, as well as dose-independent chemical sensitivity—are nearly always associated with the ORPEC state. Furthermore, clinically significant reduction in the frequency and intensity of those reactions was achieved with the use of dietary, herbal, and antifungal agents. Those observed clinical responses shed further light on the contributory roles of the ORPEC state in the pathogenesis and perpetuation of hypersensitivity states. This subject is presented at length in Dysoxygenosis and Oxystatic Therapies, the third volume of The Principles and Practice of Integrative Medicine.53


Chemical sensitivity is a state of exquisite sensitivity in which a person reacts strongly to exposure to chemicals in amounts that are tolerated by nonsensitive subjects without any ill effects. A classical example of chemical sensitivity is a person who develops headache, confusion, and tachycardia within minutes of exposure to formaldehyde in a hospital laboratory, when others in the facility feel no discomfort. I cite here an illustrative example of a variant of this disorder. One of my associate pathologists could tolerate exposure to formaldehyde fixative used for preserving surgical specimens without headache when she processed such samples on two noncontiguous days of the week. However, when unexpected schedule changes compelled her to process formalized specimens on two contiguous days of the week, she developed severe headache, illustrating the concept of cumulative total load of chemicals. The clinical symptom-complexes of chemical sensitivity have been comprehensively described and its pathogenesis discussed at length. For detailed information, I highly recommend William Rea’s four-volume classic on the subject entitled Chemical Sensitivity: Tools of Diagnosis and Methods of Treatment. 54

What are the primary pathogenetic mechanisms involved in chemical sensitivity? This question can be answered in only a conceptual mode at this time. My own sense is that chemical sensitivity is an electrochemical derangement in which the neurotransmitter dynamics are initially altered by substantial cumulative initial injury and later perpetuated by what may seem to be minor triggering exposures. The essential nature of that neurotransmitter disruption is hyper-responsiveness, the brunt of which is borne by the autonomic nervous system. Thus, oxidative-dysoxygenative dysautonomia—in my view —is the principal pathogenetic mechanism of chemical sensitivity. I saw objective evidence for that view in autonomic dysfunction delineated by power spectral scan studies of R-R wave variability in all of my patients with chemical sensitivity. I have presented this subject at length in Integrative Cardiology, the sixth volume of The Principles and Practice of Integrative Medicine.55

As for the treatment, chemical sensitivity is one of the most exasperating disorders. Infrequently I have seen patients who made a seemingly complete recovery following periods of disabling illness. It seemed to me that such cases had responded more to therapies designed to restore oxygen homeostasis and redox equilibrium through restoration of the bowel, blood, and liver ecosystems. As a rule, however, persons with long-standing chemical sensitivity show a modest to moderate degree of clinical responses and relapses are common following common deoxygenizing threats, such as exposure to mycotoxins, infectious processes, emotional stresses, and chemical insults.

Not surprisingly in view of incremental stress on human oxygen homeostasis, the incidence of chemical sensitivity is rising—and can be expected to continue to do so, as I previously pointed out in section II.


Mold-induced ill health—in my view—is the most crucial aspect of all types of hypersensitivity reactions.56,57 For that reason, proper diagnosis and desensitization with clinically relevant mold antigens and optimally administered antifungal regimens should be deemed as the central part of an integrative management plan. The spectrum of mold-related illness includes: (1) classical allergic reactions caused by mold antigens with specificity for IgE antibodies; (2) mold-induced non-Ige-mediated immunologic responses; (3) symptoms triggered by mycotoxins; (4) bowel symptom-complexes caused by mold (yeast) overgrowth; (5) increased gut permeability secondary to mold overgrowth; (6) biologic consequences of the ORPEC state; and (7) vulnerability to yeast infections due to any combination of the above factors. Needless to point out, all of the above mold (yeast)-related derangements put oxygen homeostasis and redox equilibrium in jeopardy, directly or indirectly.

The details of the diagnosis and desensitization with mold antigen for long-term clinical benefits—including but not confined to normalization of Th1 and Th2 functionalities—have been furnished in Integrative Immunology, the fourth volume of The Principles and Practice of Integrative Medicine.58


I consider therapies for bowel cleansing and liver detoxification essential for integrative treatment plans of hypersensitivity disorders of all ilk. I have marshaled extensive biochemical, morphologic, and clinical evidence for my view in Integrative Nutritional MedicineLooking Through the Prism of Oxygen Homeostasis, the fifth volume of The Principles and Practice of Integrative Medicine.59 In that volume, I also provide specific information about nutrient-herbal formulations as well as detoxification procedures, the efficacy of which I have validated with extensive clinical work.

Empirically validated therapies for bowel cleansing and liver detoxification comprised the core of therapeutic regimens for all chronic illnesses in the ancient Ayurvedic, Chinese, and classical Greek treatises. The focus of the indigenous African therapies—taught essentially by oral tradition—was also on remedies that we now know affect the bowel and the liver. Those healing arts were preserved by the naturopathic community during the intervening centuries. The reader is referred to The History and Philosophy of Integrative Medicine, the second volume of The Principles and Practice of Integrative Medicine,60 in which I establish the connectedness of the healing arts practiced in different parts of the world in those earlier eras. It is heartening to see that an ever-growing number of the so-called allopathic physicians are now beginning to adopt many of those ‘naturopathic’ therapies. In Table 1, I furnish guidelines for dosage schedules for nutrients my colleagues at the Institute and I prescribe to support our programs for patients with hypersensitivity syndromes.

Table 1. General Guidelines for Nutrient and Redox-Restorative Supplements for Atopic Patients With and Without Indolent Immune Disorders

Atopic Individuals With Chronic Indolent Immune Dysfunction

Atopic Individuals Without Chronic Indolent

Immune Dysfunction



C, 1,000 to 2,000 mg

E, 200 to 400 IU

A, 5,000 to 7,500 IU

D, 100 to 250 IU

B-complex, 25-50 mg

B12, 1,000 mcg weekly for 4 weeks


C, 3,000 to 5,000 mg

E, 400 to 800 IU

A, 10,000 to 15,000 IU

D, 100 to 250 IU

B-complex, 30-50 mg

B12, 1,000 to 5,000 mcg weekly for 4 – 6 weeks


Magnesium, 1,000 to 1,500 mg

Calcium, 750 to 1,000 mg

Potassium, 200 to 400 mg

Chromium, 100-300 mcg

Selenium, 100-300 mcg

Molybdenum, 100-300 mcg

Magnesium, 1,500 to 2,500 mg

Calcium, 1,000 to 1,500 mg

Potassium, 400 to 600 mg

Chromium, 400-600 mcg

Selenium, 400-600 mcg

Molybdenum, 400-600 mcg

Redox-Restorative Substances

Glutathione, 200-300 mg

N-acetylcysteine, 200-300 mg Methylsulfonylmethane, 200 to 500 mg Lipoic acid, 100 to 200 mg

Taurine, 500 to 1,000 mg

Coenzyme Q10, 30 to 50 mg

Pycnogenol, 50 to 100 mg

Glutathione, 600-800 mg

N-acetylcysteine, 600-800 mg Methylsulfonylmethane, 1,000 to 1,500 mg

Lipoic acid, 300 to 500 mg

Taurine, 1,500 to 2,000 mg

Coenzyme Q10, 100 to 150 mg

Pycnogenol, 100 to 150 mg


I liberally prescribe direct oxystatic therapies to restore oxygen homeostasis and redox equilibrium for all my patients with hypersensitivity syndromes. Such therapies include oxygen by mask (3 to 5 liters per minute for 30 to 60 minutes), hydrogen peroxide soaks and baths, intravenous infusions of hydrogen peroxide and ozone, and topical ozone injection therapies (discussed in my May 2005 column). For detailed information of such protocols, see Dysoxygenosis and Oxystatic Therapies, the third volume of The Principles and Practice of Integrative Medicine. 61


In February 2002, a 36-year-old woman consulted me for a progressive and incapacitating chemical sensitivity of a three year duration. Prior to developing chemical sensitivity, for three years she had suffered disabling chronic fatigue, persistent diffuse myalgia, frequent sore throat, recurrent yeast vaginitis, and air hunger. Her body weight had fallen from 123 to 100 pounds. During the first year of integrative management with antigen-specific immunotherapy, vigorous oxystatic therapies, bowel and liver detox measures, and endocrine support, she showed steady and satisfactory improvement in all her symptoms except those of chemical sensitivity. Then she received doxycycline for putative Lyme disease from another practitioner and had a full blown relapse. A psychiatrist prescribed paroxetine. In February 2005, she participated in a special healing prayer session at her church. The following are excerpts of her conversation during a visit on June 1, 2005 (the day of submission of the manuscript for this column):

“I am back on my full schedule. I could not wash any dishes or do laundry for over three years, nor could I go to grocery shopping. Since the February prayer period, I have been making steady progress. Now I am back to my full household schedule. Doing dishes and laundry would mean nothing to another person but for me it was uplifting. It means I’m normal again. I am not tired and have little, if any tissue pain. I have gained 13 pounds. I was so sick I nearly died.

“I am a woman of the word…the word of God. I have always believed God as a healer. It doesn’t matter to me who He heals me through. I work on being a receiver. I try to do my part. If I had not gotten better in another three years, I wouldn’t have lost my faith. In 2002, my 6-year-old daughter wrote the following for the X-mas wish. ‘I pray that my mom gets better and that I go to Disney World.’ Would you believe that my daughter’s class got picked up by Disney World to go there and dance. Would you believe we are going to Disney World with her.”

“I believe that if I had been healed suddenly, I would have gone to the old ways of unhealthy eating and unhealthy home environment. What would I say to a doctor who is skeptic of my healing story? Well, I almost died. I was really sick. I was desperate. I would tell him this: I know some of my doctors didn’t believe I was sick. If you as a physician can heal, why can’t God heal? Doctors are really in God’s business. They should recognize that.”


In 2000, I put forth the oxidative-dysoxygenative model of hypersensitivity to provide scientific basis and rationale for integrating prevailing immunotherapeutic measures with naturopathic oxystatic therapies for improved clinical outcome. Chronic hypersensitivity disorders can be exasperating and dispiriting, both for the patient and the physician. Chronic stress of unrelenting reactions eventually leads to anxiety and depression of varying degrees. This is especially true of chemical sensitivity, which regrettably continues to be labeled as ‘psychiatric illness’ by many. Two elements are important to recognize in this context: (1) Persons with hypersensitivity illnesses are not immune to the tyranny of neurotransmitters and the misconduct of genes, thus setting the stage for otherwise unexplained sadness and/or depression; and (2) unrelenting suffering creates its own pattern of disrupting neurotransmitter functionalities. Together, those two elements wreak havoc on many victims of hypersensitivity disorders. Ah, if only we physicians could have Solomon’s wisdom and Zoroaster’s patience for coping with those odds!


1. Ali M. Spontaneity of Oxidation in Nature and Aging (monograph), Teaneck, New Jersey. 1983.

2. Ali M. Oxidative regression to primordial cellular ecology (ORPEC): evidence for the hypothesis and its clinical significance. J Integrative Medicine 1998;2:4-55.

3. Ali M: Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine 1999;3:11-16.

4. Ali M. Recent advances in integrative allergy care. Current Opinion in Otolaryngology & Head and Neck Surgery 2000;8:260-266.

5. Ali M. Oxidative coagulopathy in environmental illness. Environmental Management and Health 2000;11:175-191.

6. Holland HD. The Chemistry of Atmosphere and Oceans, Wiley, New York 1978.

7. Knoll AH. Breathing room for early animals. Nature 1996;382:111-112.

8. Dwyer JJ, Burnett LE. Acid-base status of the oyster Crassostrea virginica in response to air exposure and to infections by Perkinus marinus. Biol Bulletin 1996;190:139-147.

9. Cooper SR, Brush GS. Long-term history of Chesapeake Bay anoxia. Science 1991;254:992-994.

10. “Climate and the Rise of Man,” U.S. News & World Report, June 8, 1992.

11. “Global warming: It’s here…,” Time magazine, August 24, 1998.

12. Shaw W. Role for certain yeast and bacteria byproducts discovered by organic acid testing in the etiology of a wide variety of human diseases. Bulletin of The Great Plains Laboratory, Overland Park, KS 66204.

13. Puppo A, Halliwell B. Formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Is haemoglobin a biological Fenton catalyst? Biochem J 1988;249:185-190.

14. Gutteridge JMC, Halliwell B. Radical-promoting loosely bound iron in biological fluids and the bleomycin assay. Life Chem Rep 1987;4:113-142.

15. Richet, C & Porter P. De l’action anaphylaique de certains venins. C R Soc Biol (Paris) 1902; 54:170.

16. Von Pirquet, C. Allegie, Muench Med Wochenschr 1906;53:1457. In Gell & Coombs (eds.) Clinical Aspects of Immunology, Philadelphia, FA Davis Co. 1963:40.

17. Noon L. Prophylactic inoculation against hayfever. Lancet 1911:1:1572.

18. Coca AF & Cooke RA. On the classification of the phenomena of hypersensitiveness. J Immunol 1923; 8:163.

19. Prausnitz C & Kustner H. Studien uber die Uberempfindlichkeit. Zentralbl Bakteriol (Orig A) 1921: 86:160.

20. Coombs RRA & Gell PGH. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: Gell & Coombs eds. Clinical Aspects of Immunology, Oxford, Blackwell Scientific Publications 1963:575-596.

21. Ishizaka K, Ishizaka T, & Hornbrook MM. Physicochemical properties of reaginic antibody. V. Correlation of reaginic activity with E globulin antibody. J Immunol 1966; 97:840.

22. Wide L, Bennich H, & Johansson SGO. Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet 1967; 2:1105.

23. Ali M, Mesa-Tejada R, Fayemi AO, Nalebuff DJ, Connell JT. Localization of IgE in tissues by an immunoperoxidase technique. Arch Pathol Lab Med 1979;103:274-275.

24. Ali M, Fayemi AO, Nalebuff DJ. Localization of IgE in adenoids and tonsils: an immunoperoxidase study. Arch Otolaryngol 1979;105:695-697.

25. Ali M & Ramanarayanan MP. A computerized micro-ELISA assay for allergen-specific IgE antibodies. Am J Clin Pathol 1984;81:591.

26. Ali M, Ramanarayanan MP, Nalebuff DJ, et al. Serum concentrations of allergen-specific IgG antibodies in inhalant allergy: effect of specific immunotherapy. Am J Clin Pathol 1983;80:290.

27. Hurst D, Weekley M, Ramanarayanan M. Evidence of possible localized specific immunoglobulin E production in middle ear fluid as demonstrated by ELISA testing. Otolaryngol Head Neck Surg 1999;121:224-30.

28. Randolph TG. Human Ecology and Susceptibility to the Chemical Environment, Springfield, IL, Charles C. Thomas 1962.

29. Rea WJ. Clinical ecology: a role in diagnosing environmental illness. Annual New England Occupational Medicine Association Conference, Harvard School of Public Health 1987.

30. Waickman FJ & Vojdani A. Putting chemical and environmental sensitivities in perspective. Otolaryngologic Clinics of North America, Vol. 31, No. 1, Feb. 1998.

31. Selye H. The general adaptation syndrome and the diseases of adaptation. J Allergy 1946;17:23-31.

32. Kahn E & Letz G. Clinical ecology: environmental medicine or unsubstantiated theory? Ann Int Med 1989;111:104-6.

33. Sparks PJ, Daniell W, Black DW, et al. Multiple chemical sensitivity syndrome: a clinical perspective. J Occupational Medicine 1994;36:718-737; Cullen MR. The worker with multiple chemical sensitivities: an overview. State Art Rev Occup Med 1987; 2:655-661.

34. Li N, Sioutas C, Cho A, et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect 2003;111:455-60.

35. Xiao GG, Wang M, Li N, et al. Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J Biol Chem 2003;278:50781-50790.

36. Lima H-B, Ichinosea T, Miyabaraa Y, et al. Free Radical Biology and Medicine 1998;25:635-644.

37. Gurgueira SA, Lawrence J, Coull B, et al. Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ Health Perspect 2002 Aug;110(8):749-55.

38. Nel A. Air pollution-related illness: effects of particles. Science 2005;308:804-806.

39. U.N. Environment Program and WHO Report, Environment 1994;36:4.

40. Health Effects Institute Perspectives,, April 2002 report.

41. National Academy of Sciences, National Research Council, Research Priorities for Airborne Particulate Matter: I–Immediate Priorities and a Long-Range Research Portfolio, National Academy of Sciences, Washington, DC 1998.

42. Donaldson K & Tran CL. Inflammation caused by particles and fibers. Inhal Toxicol 2002;14:5.

43. Li N, Sioutas C, Cho A, et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect. 2003 Apr;111(4):455-60.

44. Silbajoris R, Ghio AJ, Samet JM, et al. In vivo and in vitro correlation of pulmonary MAP kinase activation following metallic exposure. Inhal Toxicol. 2000; 12:453-68.

45. Brook RD, Franklin B, Cascio W, et al. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation. 2004;109:2655-71.

46. Nel AE, Diaz-Sanchez D, Ng D, et al. Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system. J Allergy Clin Immunol. 1998102:539-54.

47. Lim HB, Ichinose T, Miyabara Y, et al. Involvement of superoxide and nitric oxide on airway inflammation and hyperresponsiveness induced by diesel exhaust particles in mice. Free Radic Biol Med. 1998;25:635-44.

48. Ghio AJ, Devlin RB. Inflammatory lung injury after bronchial instillation of air pollution particles. Am J Respir Crit Care Med. 2001;15;164(4):704-8.

49. Li N, Alam J, Venkatesan MI, et al. Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals. J Immunol. 2004;173:3467-81.

50. Xiao GG, Wang M, Li N, Loo JA, Nel AE. Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J Biol Chem. 2003;278:50781-90.

51. Nemmar A, Hoet PH, Vanquickenborne B, et al. Passage of inhaled particles into the blood circulation in humans. Circulation. 2002;106:e141-2.

52. Kelly FJ, Sandstrom T. Air pollution, oxidative stress, and allergic response. Lancet. 2004;10;363(9403):119-25.

53. Ali M. The Principles and Practice of Integrative Medicine Volume III: Dysoxygenosis and Oxystatic Therapies. Washington DC, Capital University Press (in collaboration with Canary 21 Press, New York)( 2003.

54. Rea WJ. Chemical Sensitivity: Tools of Diagnosis and Methods of Treatment (Volumes 1-4), Lewis Publishing, Dallas, TX 1997.

55. Ali M. The Principles and Practice of Integrative Medicine Volume VI: Integrative Cardiology. Washington, DC., Capital University Press (in collaboration with Canary 21 Press, New York) ( & 2003.

56. Ali M, Nalebuff DJ, Fadal RG, Fayemi AO: The RAST in clinical practice: great expectations, disillusionment and renewed confidence. In Fadal RG, Nalebuff DJ (eds.): RAST in Clinical Allergy, Chicago, Year Bk Med 1981;321-328.

57. Ali M. In vitro monitoring of immunotherapy with serial management of serum levels of allergen-specific IgG antibodies. Otolaryngologic Clinics of North America 1985;18:761-774.

58. The Principles and Practice of Integrative Medicine Volume IV: Integrative Immunology and Allergy: The Oxidative-Dysoxygenative Perspective. Washington DC, Capital University Press (in collaboration with Canary 21 Press, New York) ( 2003.

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