Oxygen Model of Inflammation

OXYGEN GOVERNS THE INFLAMMATORY RESPONSE AND ADJUDICATES MAN-MICROBE CONFLICTS

Majid Ali, M.D.

Life is an unending injury-healing-injury cycle. Injury is inevitable in an organism’s struggle for survival. Healing is the intrinsic capacity of the organism to repair damage inflicted by that injury. Inflammation — in my view — is one aspect of the energetic-molecular mosaic of that intrinsic capacity. This view of inflammation — that it is a physiologic component of the essential injury-healing-injury nature of life — extends far beyond the classical and wholly inadequate notion of it being a process characterized by edema, erythema, tenderness, pain, and infiltrate of inflammatory cells. Since oxygen is the organizing influence of human biology and governs the aging process in humans, it follows that inflammation, first and foremost, is one of the many face of oxygen homeostasis. In 1990, I devoted a large part of Oxygen and Aging to this subject.1

At a bioenergetics level, inflammation in any part of the body is inflammation in all parts of the body, albeit to varying degrees. Ulcerative colitis is chronic inflammation involving large segments of colon. Gall stones are nearly always associated with inflammation in the wall of the gall bladder, albeit to varying degrees. So it should not be surprising that ulcerative colitis is commonly associated with gall bladder, in 45% of cases in some reports. A type of chronic inflammation of bile ducts called sclerosing cholangitis occurs in about 10% of the colitis cases.

Uveitis, a type of eye inflammation occurs in about 25%.


Three Message

First, all inflammation at its root is an oxygen problem.

Second, the more the areas of inflammation in the body you can detect and address, the better the clinical results.

Third, please learn to use spices, oil rubs, and related natural anti-inflammatory remedies.

For more information, please consider my recipes at this site.


Two Core Concepts of Crucial Clinical Significance

Below, I state two core concepts of crucial clinical significance that evolved from the view of inflammation given above:

1. Physiologic inflammation becomes pathologic inflammation when oxygen homeostasis is in jeopardy; and

2. The status of oxygen homeostasis determines the outcome in man-microbe conflicts. In this context, oxygen also resolves the long-standing Pasteur-BeChamp controversy about whether disease is caused by microbes invading from outside or by microzyma proliferating from within.

Oxygen homeostasis has not been a consideration of immunologists and infectious disease specialists. It needs to be. Nor has oxygen been of interest to pediatricians, internists, and family practitioners who are the most frequent prescribers of antibiotics, since they take their cues from the specialists. I believe this is the primary factors that leads to massive abuse of aantibiotics. In a chapter entitled “Oxygen Settles the Great Pasteur-BeChamp Debate” in Oxygen and Aging, I summarized my view of that matter with the following words:

When oxygen metabolism is optimal, Pasteur’s microbes from outside play more important roles in causing infectious disease. When oxygen metabolism is dysfunctional, BeChamp’s life forms multiplying from within the body become more important. 6

On the surface, the above statement flies against the face of the prevailing model of microbiology. However, that conclusion seemed inescapable to me as I searched for some unifying principle in the diverse and disparate data concerning patients who had received extensive antibiotic therapy without clinical benefits. (‘Why do bring oxygen into everything?’ a patients asked me once. ‘If you were designed to run on gasoline, I would bring gasoline into every thing’, I replied, then added, ‘If you were silicon-based, I would bring silicon into every consideration of your health and illness.’)

In this column, I reproduce some text from earlier publications and offer brief commentary to eloborate and validate the above two core concepts of crucial clinical significance stated above. I do not believe that any of the so-called mystery maladies — recurrent otitis media in infants to ADHD in children to disabling fatigue in adolescents to multiple sclerosis in men to endometriosis in women to incapacitating myalgia in seemingly healthy persons to Alzheimer’s disease in the elderly — can be understood without understanding how oxygen separates the state of health from states of absence of health and disease. Nor, in my view, can any of the mystery inflammatory and infectious syndromes — chronic lyme disease to indolent Epstein-Barr infection to ‘yeast’ problems to the so-called nanobacterial lesions — be understood or managed effectively without knowing the primary signalling functions of oxygen. In this column I include text from earlier publications in which I described some of my clinical and laboratory observations, reflections, and insights that led to the two core clinical concepts stated above. Specifically, those sections include: (1) spontaneity of oxidation in nature; (2) Many Dr. Jekyll/Mr. Hyde roles of oxygen and taming of the oxygen-shrew; (3) oxidative coagulopathy; (4) oxidative regression to primordial cellular ecology; (5) dysoxygenosis; (6) resolution of the Pasteur-BeChamp controversy by oxygen; and (7) history of oxygen and the age of dysoxygenosis. I close this column with brief comments about a disturbing disconnet between the scientific knowledge of the efficacy of oxygen therapies for treating infectious disorders and the total neglect of such therapies by doctors preoccupied with antibiotics.

1. SPONTANEITY OF OXIDATION

In 1983, in Spontaneity of Oxidation in Nature and Aging,7 I included the following text to recognize spontaneity of oxidation as the primary drive — essentially provided by oxygen for all developmental, differentiative, and death-related processes in the health/dis-ease/disease continuum of human life.

Oxidation is nature’s grand design for assuring that no life form lives forever. Nature made oxidation a spontaneous process. It requires no expenditure of energy. It needs no external cues or outside programming. In scientific jargon, oxidation is defined as loss of electrons by atoms and molecules. A molecule is a group of atoms bonded together. Electrons are the tiniest packets of energy. When atoms and molecules lose electrons, they lose energy. In oxidation, high-energy atoms and molecules are changed into lower-energy atoms and molecules. This is the essence of the phenomenon of aging.

Human frames age when their body organs age. Human body organs age when their tissues age. Human tissues age when their cells age. Human cells age when their molecules age. Human molecules age when they lose their plasticity. How do molecules lose their plasticity? By oxidative injury. Oxidative molecular damage, then, is the basic mechanism of ongoing molecular aging.

Clinical Significance of Spontaneity of Oxidation

Oxidative injury in each and every disease process — once initiated, regardless of the initiating agent — takes on a life of its own, and is perpetuated by the mechanisms of spontaneity of oxidation in nature. Thus, arrest of that oxidative injury is essential in the treatment of each and every disease. Antioxidants, I might add for clarity, alone are not sufficient. I might also add here that fires that stoke spontaneity of oxidation largely burn in the bowel, blood, and liver ecosystems. That explains why I do not believe any treatment plans any subacute and chronic disorders can be considered complete if such plans do not fully address those ecologic issues.

2. MANY DR. JEKYLL/MR. HYDE ROLES OF OXYGEN AND THE TAMING OF THE OXYGEN SHREW

Below is some text from Oxygen and Aging that summarizes my viewof oxygen, the ultimate spin doctor8:

Oxygen is the conductor of the orchestra of life. It is a life giver and a life exterminator. It is the ultimate spin doctor of biology. Oxygen causes cell death by its presence as well as by its absence. Oxygen is the ultimate molecular Dr. Jekyll and Mr. Hyde. It is the spark for the furnace of human metabolism. It is the primary nutrient of life. It is the primary detox molecule of the body. It turns poisons into harmless materials and innocent substances into poisons. Oxygen is nature’s primary antibiotic. Oxygen referees the match between a hunter immune cell and a microbe. Then, it determines who wins that match. In the same way, it referees the match between a hunter immune cell and a cancer cell, then determines who wins. When needed, it becomes a hormone (by picking up an extra electron).

Molecular oxygen has an interesting “love-hate” relationship with electrons. It avidly picks up free electrons in its vicinity, then just as avidly spins them out. During the production of ATP with oxidative phosphorylation, the safe molecular oxygen steals an electron and becomes an unsafe free radical called superoxide. How did all that happen?

One day I stood before a statue of Zeus seducing Lydia at the Metropolitan Museum of Art in New York City. Mesmerized by the stunning beauty of the statute, it seemed to me that the ancient Greeks had an answer for everything. Could it be that they also had an answer for my oxygen riddle as well? It occurred to me those Greeks must have understood oxygen well. How else could they create Zeus, their supergod, so perfectly in its image?

Zeus suffered from attention deficit and hyperactivity syndrome. Like oxygen, Zeus was a Dr. Jekyll-Mr. Hyde without peer among the Olympian immortals. He was well known for throwing unprovoked temper tantrums just like oxygen. He struck hapless mortals with his thunderbolt, often without knowing why he did so. He was promiscuous. He tried to make love to everything that moved, again just like oxygen just like oxygen. . Who could have been the role model for Zeus?, I wondered. Oxygen alone, I recognized, could have been his inspiration. In the museum statue, Zeus climbed Lydia in the form of a swan. He often turned himself into animal forms to escape the notice of Hera, his wife, during his sexual escapades. (Looking at Zeus’ swan, my mind drifted to two recent young American presidents who also had the same inclinations. Who was the role model of those lustful presidents, Zeus or oxygen?, I wondered.)

So, how does oxygen keep peace and incite riots of free radicals at the same time? The statue of the swan gave me the answer. Zeus begot Athena, the goddess of wisdom. Athena, we are told, gave the Greeks their sense of order and civility. Athena, we are also told, had a way with Zeus, just as many cool and collected daughters have with their volatile dads. She knew how to pacify her old man. So far, so good. But, how did the Greeks figure that out? In whose image did those clever Greeks create goddess Athena?, I wondered. Enter ATP.

Clinical Significance of the Oxidative Coagulopathy

In Greek mythology, the benevolent and impetuous supergod Zeus created their benevolent and impetuous supergod Zeus in oxygen’s image. Then they created the wise Athena in ATP’s image. Oxygen begot ATP, just as Zeus begot Athena. Then ATP tames oxygen, just as Athena tamed Zeus. ATP’s Athena was the answer to the shenanigans of oxygen’s Zeus. The answer to the volatile unpredictability of the dad was hidden in the wisdom and dependability of the daughter. The Swan-Lydia statute seemed to unravel the oxygen riddle. ATP, the prime energy molecule in the body, conducts all energy transactions in the cells, but does so without any of oxygen’s volatility — which, of course, is ever ready to display its dirty hand when given a chance. In all nutritional, ecologic, autoimmune, infection, and degenerative disorder, the oxygen Zeus (spontaneity of oxidation) provides the essential drive for perpetuating and worsening molecular and cellular injury. In reversing those disorders, we physicians need to look toward ATP athena (mitochondrial functionality) for steadiness and stability.

3. OXIDATIVE COAGULOPATHY

Following is an abstract of an article my colleague Omar Ali and I published in The Journal of Integrative Medicinethe to relate the subjects of spontaneity of oxidation and molecular duality of oxygen to the most significant degenerative disorder of our time, coronary artery disease9:

We propose that ischemic heart disease (IHD) is caused by “AA oxidopathy”—a state of accelerated oxidative molecular injury to blood corpuscles and plasma components. Although AA oxidopathy eventually results in the formation of “microclots” and “microplaques” in the circulating blood, it begins with oxidative permutations of plasma sugars, proteins, lipids and enzymes, and is not merely confined to oxidative activation of recognized coagulation pathways that we collectively designate as “oxidative coagulopathy.” AA oxidopathy comprises localized areas of blood cell damage and congealing of plasma in its early stages, fibrin clots and thread formation with platelet entrapment in the intermediate stages, and “microclot” and “microplaque” formation in late stages. Such changes can be directly observed in peripheral blood smears with high-resolution phase-contrast and darkfield microscopy. As observed microscopically, the early changes of oxidative coagulopathy are reversible and constitute what we designate as “clotting-unclotting equilibrium (CUE).” The AA oxidopathy hypothesis seeks to establish oxidative “clotting-unclotting disequilibrium (CUD)” and related molecular and cellular events occurring in the circulating blood as the primary pathogenetic elements of IHD, and the patterns of tissue injuries taking place in the vessel wall (atheroma formation, scarring and rupture) as consequential events. Coronary vasospasm and membrane depolarization dysfunctions of myocytes as well as of the conducting system of myocardium are induced by AA oxidopathy and constitute nonatherogenic components of IHD.9

Clinical Significance of the Oxidative Coagulopathy

The oxidative coagulopathy model of ischemic coronary heart disease challenges two fundamental assumptions of the prevailing cholesterol, inflammatory, infectious, autoimmune and gene hypotheses of ischemic heart disease: 1) that IHD is caused by initial tissue injury occurring in the arterial wall; and 2) that optimal therapeutic approaches must focus on lowering blood cholesterol levels and/or revascularization procedures such as angioplasty and coronary bypass surgery.

4. OXIDATIVE REGRESSION TO PRIMORDIAL CELLULAR ECOLOGY

In 1998, I presented a very body of morphologoc observations — made with ihigh-resolution phase-contrast microscopy) to deal with contentious issue of whether the circulating blood is a sterile field. Following is an abstract of that article published in The Journal of Integrative Medicine10:

In clinical states characterized by chronically accelerated oxidative stress, enzyme systems involved in oxygen transport and utilization, redox regulation, and acid-base equilibrium are severely impaired. Such oxidative states include fibromyalgia, chronic fatigue syndrome (CFS), Gulf War syndrome, severe immune disorders, and malignant neoplasms. It is proposed that normal “oxygenative” cellular ecology in such states undergoes an “oxidative regression to primordial cellular ecology” (ORPEC) in which state progressive anoxia, acidosis, excess reactive oxidative species, and accumulation of certain organic acids create cellular ecologic conditions that closely simulate the primordial state. The ORPEC state results in rapid multiplication in blood and tissues of pleomorphic anaerobic organisms with yeast-like morphologic features, which are designated “primordial life forms” (PLFs) for lack of precise nucleotide sequence and taxonomic data. PLFs are readily observed with high-resolution phase-contrast and darkfield microscopy in freshly prepared and unstained smears of peripheral blood. Strong homology among yeast and mammalian DNA sequences indicates that the genetic codes for PLF growth may already exist in human cells and that organisms observed in this study may not indicate an infection from an outside source. Rather, the clinical syndromes associated with PLF proliferation may represent a novel “microecologic-genetic” model of illness. Organic acids and other toxins produced by the growing number of PLFs further feed the oxidative flames of the ORPEC state, thus generating oxidative cycles that feed upon each other and are damaging to antioxidant and oxygenative enzyme systems of the body.10

Clinical Significance of the ORPEC State

The clinical significance of the ORPEC hypothesis is that: (1) it provides a sound scientific model for a clearer understanding of the pathogenesis of syndromes associated with accelerated oxidative molecular injury, such as fibromyalgia, CFS, Gulf War syndrome, severe autoimmune disorders and malignant tumors; and (2) it provides a framework for a rational and logical approach for repairing oxidatively damaged cellular ecologies and for restoring health. Notwithstanding the lack of nucleotide sequence and taxonomic data concerning PLFs, the ORPEC hypothesis has strong explanatory power for: (1) the morphologic patterns of growth of PLFs documented in this report; (2) the pathogenesis of clinical syndromes characterized by accelerated oxidative injury; and (3) the sound scientific basis and/or rationale for the empirical efficacy of “anti-PLF”

oxygenative, antioxidant, and other therapies employed to restore cellular ecology from the ORPEC state to a physiologic, healthful condition.

To support the ORPEC hypothesis, I drew draws its primary support from the microscopic findings presented in this paper when these are considered in light of the following: (1) the fundamental “oxygen order” of human biology; (2) the history of oxygen during the primordial era; (3) the primordial cellular ecology as reconstructed from the origin-of-life studies; (4) morphologic evidence of accelerated oxidative injury to all components of circulating blood (oxidative coagulopathy), and to cell membranes, intracellular matrix, and cell organelles such as mitochondria (AA oxidopathy); (5) oxidative oxygenative dysfunctions (pathologic states characterized by impaired cellular oxygenation and caused by oxidative injury); (6) a high level of homology among yeast and mammalian nucleotide sequences (reflecting conserved primordial nucleotide sequences) that may lead to de novo growth of PLFs under primordial conditions; (7) phenomenon of gene swapping in nature that may enlarge the cellular genetic pool ; (8) oxidative 3 C cascades that contribute to and perpetuate primordial conditions; (9) evolving concepts of mycosis and PLFs; (10) increased urinary excretion of certain organic acids that provide biochemical evidence of overgrowth of yeast and PLFs in patients in the ORPEC state; and (11) clinical syndromes of accelerated oxidative molecular injury. 11-14

The core ecologic concept presented in this article is simply stated: No cause of human suffering may be sought in any individual biologic event, divorced from the larger ecologic elements that affect the human condition. Specifically, the cause of oxidative regression to primordial cellular ecology may not be searched in individual oxidative triggers. Rather, the microecologic-genetic shift of the ORPEC state represents the sum total of cumulative oxidative stressors.

5. Dysoxygenosis

In 1998, I introduced the term dysoxygenosis for a state of partial or complete failure of oxygen utilization in cells.18,21,22 I put forth the hypothesis that dysoxygenosis is caused by impaired function of enzymes involved in oxygen homeostasis (“oxyenzymes”) and leads to altered expressions of genes induced by hypoxic environment (“oxygenes”). The webs of oxyenzymes are vast, with each entity linked to every other through multiple pathways. The webs of oxygenes are seemingly far more complex. All such webs are exquisitely ‘aware’ of changes in oxygen availability in their microenvironment and vigorously respond to them. When one thing changes in those webs in one way, everything changes in some way. Dysoxygenosis, then, is discerned as a state caused by a rich diversity of elements but one that creates the same cellular oxygen dysfunction. In 1998, I also introduced the terms dysfunctional oxygen metabolism and oxygen disorder for readers without medical or biochemical background.15

Clinical Significance of Dysoxygenosis

A clear understanding of that yield/rate trade-off between the fermentative and respiratory ATP-producing pathways is of crucial importance to a clear understanding of the clinical significance of dysoxygenosis. The primary biochemical evidence for dysoxygenosis presented here concerns increased urinary excretion of metabolites of the Krebs cycle and glycolytic pathways for generation of ATP. In essence, such organic acid excretion represents a costly metabolic error. The acids were ‘packages’ of energy that were not processed in the ATP-producing pathways and were ‘returned unopened.’ Put in other words, urinary waste is a clear and unequivocal indication of regression of the metabolic mode from ‘energy-effective’ respiratory ATP-producing pathway to an ‘energy-inefficient’ partially fermentative ATP-producing pathway. That core issue is illustrated below.

Of central importance in such analysis are the intermediates of the citric acid (tricarboxylic or Krebs) cycle. In health, this cycle is the true crossroads of both the anabolic and catabolic energetics. It is the final common pathway for oxygen-driven breakdown of sugars, fats, and proteins for serving the energy needs of the body. It also provides for the oxygen-driven synthesis of the basic building blocks for structural and functional molecules of the body. All steps in this cycle of energetics are catalyzed by a variety of enzymes and their cofactors. Metabolic pathways of carbohydrates, lipids, and proteins enter the cycle via acetyl CoA derived from pyruvic acid, fatty acids, and amino acids respectively.75,76,76a,76b Theoretically, blockages at various levels in the Krebs cycle can be produced when: (1) The cycle enzymes are inactivated by endogenous and exogenous noxious substances; (2) .The functions of enzymes are hampered by factors such as pH, temperature, or changes in the quality and quantity of substrates; (3) The cycle enzymes are in short supply or imperfectly produced— enzymes are proteins produced by expression of genes that encode them; (4) The enzyme cofactors are in short supply due to nutritional factors; and (5) There are mitochondrial inefficiencies that interfere with optimal enzyme functions. It may be added here that Krebs cycle metabolites(succinic acid, ketoglutaric acid, and others — regarded as mere waste products in the past — are now known to serve cruially important signalling functions.16,17

6. OXYGEN SETTLES THE GREAT PASTEUR-BeCHAMP DEBATE

Below, I reproduce some text from Oxygen and Aging to briefly address a bitter controversy among mainstream doctors and integrative clinicians.

Louis Pasteur, a 19th-century French chemist, introduced the germ theory and stated that specific infections are caused by specific microbes invading the body from outside. He further believed microbial species were fixed (monomorphism)1-3. Antoine de Bechamp, his opponent and a prominent microbiologist of the French Academy of Science, believed infections were caused by organisms that develop from within the body and that such organisms underwent radical changes under different conditions (polymorphism, pleomorphism). Pasteur and Bechamp showed nothing but disdain for each other’s view. Thus began the great Pasteur-Bechamp debate. Pasteur’s without versus Bechamp’s within view of the origin of diseases controversy persists.

During the 150 years after Pasteur, most mainstream doctors accepted Pasteur’s dogma as an article of faith. Indeed, many of them scoffed at the very idea of microbes developing from within. Many researchers and clinicians, on the other hand, championed Bechamp’s cause and openly laughed at the blind faith of mainstreamers. To this day, the Pasteur- Bechamp debate among persons with interest in the ecology of the blood has been usually lively, sometimes bitter, but always inconclusive.

A peculiar aspect of the Pasteur-Bechamp debate is that the leaders in Bechamp’s camp (“Bechampists”) have been passionate microscopists while Pasteur’s disciples (“Pasteurists”) have shown little, if any, inclination to use their microscopes to study the patterns of microbial growth in the blood. The ideas of Bechampists often seemed radical to their peers, but they used their microscopes with great care and persistence. In clinical medicine, they focused on changing the internal conditions of the body. The Pasteurists, by contrast, completely neglected issues of blood ecology and committed themselves to killing microbes with chemicals. Their attitude was all the more remarkable because they considered themselves scientists and took great pride in the scientific method in medicine. Yet, they refused to use their microscopes to validate or refute the findings of Bechampists. What could be more scientific than to observe directly with a microscope what populates the blood of their patients? That question never seemed to trouble them.

Pasteur was clearly right in his core belief that discrete microbial species cause discrete diseases. That view (the germ theory and monomorphism, in the context of the present discussion) requires no further validation. Strep throat is caused by Streptococcus species microbes, and tuberculosis results from infections of tuberculosis microbes (Mycobacterium). Lyme disease is caused by the Lyme spirochete (Borrella burgdorferi) and shingles by herpes virus (H. zoster). No one has ever demonstrated that tuberculosis microbes are capable of causing typical bull’s eye skin rash caused by the Lyme organism, nor has Streptococcus ever caused skin rash of the type seen in shingles. No one with even the most basic medical knowledge can question that.

Bechamp was also right. The core microscopic observations concerning pleomorphism of Beale, Almquist, Enderlein, and Naessens are accurate and reproducible and fully validate Bechamp’s core idea of life forms (microzymes, in his terminology) that exist within the human body in health and multiply under certain conditions to cause disease. As I wrote earlier, accurate physical observations are not open to question; the conclusions drawn from those findings are, and should be, open to debate.18

I might add here a historical foot note. Pasteur, the politician, appropriated to himself much of the prior knowledge of the contagion. To cite one well-documented example, the Italian scholar-physician Girolama Fracastro (1478-1553) clearly defined the concept of infectious disease caused by seminaria (small seeds) — microbial agents, in the present context. In 1530, he coined the name for syphilis — then devastating Europe — in an allegory written in Latin hexameter in which god Apollo is angered by a shepherd and afflicts him with a new disease.19 (Gould)

Clinical Significance of the Oxygen View of the Pasteur-BeChamp Debate

There is an interesting aspect of the great Pasteur-BeChamp debate which has been to light by studies of cyclicity in the incidence of syphilis (8-11 year cycles of surges) and absence of cyclicity in the incidence of gonorrhea during the same periods in the same population.21,22 That discordance in the incidences of two major sexually transmitted diseases appears to be due to differences in the host-pathogen transmission processes. In the case of syphilis, there is non-linearity produced by partial immunity following the infection — the susceptible-infected-recovered (SIR) model applies. By contrast, gonococci usually evade post-infection immunity by camouflage through varying arrays of surface proteins — the susceptible-infected-susceptible (SIS) model applies and cyclicity in the incidence is not observed.

For integrative clinicians — in my view — there are other considerations beyond the obvious questions concerning the relative importance of external factors (sexual behavior) and intrinsic pathogenicity (virulence) of the organism in the syphilis-gonorrhea comparative study. And these considerations are the crucial clinical matters of the status of oxygen homeostasis and redox equilibrium in a given individual that determine whether or not that person becomes chronically ill or rapidly recovers from the infection.

7. HISTORY OF OXYGEN

AND THE AGE OF DYSOXYGENOSIS

I close this article with brief comments about the history of oxygen on the planet earth and what may be called ‘the age of dysoxygenosis.’ A large body of evidence supports the widely held view that the history of atmospheric oxygen on the planet Earth can be divided into the following three eras5-8:

1. An era of oxygen-free, strongly reducing primordial conditions;

2. An era of accumulation of free oxygen in the atmosphere, the concentration in the ambient air eventually rising to 30 to 35 percent of the air; and

3. A period of decreasing concentration of free atmospheric oxygen, the level falling to 21 percent or lower at present.

To the above three eras, I now add a fourth era of cellular and matrix dysoxygenosis — dysfunctional oxygen metabolism within the cells, in the matrix, and within circulating fluids, such as blood and lymph.

Clinical Significance of the Age of Dysoxygenosis

In dysoxygenosis, the central issue is not the level of free oxygen in the ambient air, but how the available oxygen is metabolized in the cells of humans and animals alike.10-13 This is a state in which molecular demons unleashed by failing oxygen relentlessly corrode the body from within. That is what ails the growing masses of humans and animals suffering from those ‘mystery maladies.’ This view may surprise many doctors and public health policy makers, but—in my view—the evidence is unmistakable and incontestable.

Dysfunctional oxygen metabolism is the greatest threat to human health in the 21st century. That means we need a new “oxygen model” of diseases and a new “oxygen protocol” for controlling acite, and reversing subacute and chronic disorders. Even when surgical intervention is needed, as I illustate in a latter section of this column, the “oxygen view” has substantial clinical benefits. Below, I choose two illustrative examples of genetics of coronary artery disease and oxytherapeutics for surgical procedures to support the above statements.

OXYGEN, GENES, AND CORONARY HEART DISEASE

Genetic factors are thought to increase the risk to coronary artery disease. Large-scale gene expression analysis of approximately 12,000 human genes in severely atherosclerotic and nonatherosclerotic human coronary arteries have been conducted employing oligonucleotide microarrays. In one study (Archacki), fifty-six genes showed differential expression in atherosclerotic coronary artery tissues.22 As one would expect, increased gene expression in nearly all cases (55 genes out of a total of 56) involved genes that encode proinflammatory and oxidizing factors. Not surprisingly, the only gene with downregulated expression encodes glutathione, a potent reducing agent.

What might one make of the above findings? I think the above genetic alterations provide unequivocal evidence for the oxidative coagulopathy model of coronary heart disease. Evidently, oxidative damage to the endothelial, subedothelial stromal, and muscular components of the vascular wall (atherogenesis) triggered by initial oxidative events in the circulating blood is mediated by proinflammatory and oxidizing factors, the excess production of which requires increased expression of genes encoding them.

This is a case in which proinflammatory species are produced in small amounts initially to mediate the physiological inflammatory response which must precede healing. However, ongoing insults lead to excess production of those proinflammatory substances, which then assume destructive pathologic roles.

The downregulation of gene encoding glutathione raises a more interesting question concerning the mechanisms of redox homeostasis in pathologic gene expression. Does it simply represent an “exhaustion phenomenon” — a state in which the involved genes get ‘tired and give up’? Or, could it be there is planned downregulation of a major antioxidant system for some ulterior motive? Some as yet unsuspected dimension of redox dyshomeostasis? Nature has a sense of its own economy. Could it be that beyond a point of severe injury, Nature plays an as yet undefined card to expedite the death of severely compromised cells by suppressing some antioxidant pathways? To conserve energy for some other worthy purpose — say, for bringing many more new cells at a lower energy cost than would be required to heal what it considers to be irreversibly damaged cell?

OXYTHERAPEUTICS

There is a disturbing disconnect between the enormous body of data documenting the efficacy of oxygenative therapies — ozone, hydrogen peroxide, singlet oxygen, and others — and the use of such therapies in mainstream medicine. Even when a prestigious journal, such as The New England Journal of Medicine, publishes unequivocal proof of the efficacy of such therapy, physicians, by and large, ignore such reports. Consider the following quote from a recent issue of the Journal23:

Among the 250 patients who received 80 percent oxygen, 13 (5.2 percent; 95 percent confidence interval, 2.4 to 8.0 percent) had surgical-wound infections, as compared with 28 of the 250 patients given 30 percent oxygen (11.2 percent; 95 percent confidence interval, 7.3 to 15.1 percent; P=0.01). The absolute difference between groups was 6.0 percent (95 percent confidence interval, 1.2 to 10.8 percent). The duration of hospitalization was similar in the two groups. Conclusions The perioperative administration of supplemental oxygen is a practical method of reducing the incidence of surgical-wound infections.

When I read the above article, I wondered if the age of oxygen therapeutics had finally arrived for mainstream medicine. Some weeks later I read the letters to the editor written in response to that article. Not unexpectedly, all those were written to challenge the validity of oxygen therapy.24,25 The writers of those letters did not say that they had tried oxygen therapy and found it lacking efficacy. They just thought oxygen could not have worked. Oxygen homeostasis continues to be ignored. There is little interest in the boundary between health and a state of absence of health.26,27 Oxygen therapeutics continues to be an orphan. Who might be at blame? Perhaps those who benefit when safe, effective, and non-patentable therapies are suppressed.

References

1. Ali M. The agony and death of a cell. Syllabus of the Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1985.

2. Ali M. Intravenous Nutrient Protocols in Molecular Medicine. Monograph. Institute of Preventive Medicine, Bloomfield, New Jersey, 1987.

3. Ali M. Molecular basis of cell membrane injury. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1990.

4. Ali M. Aging-Oxidant Molecules. The Cortical Monkey and Healing. page 17, 1990. Institute of Preventive Medicine, Bloomfield, New Jersey.

5. Ali M. Spontaneity of oxidation in nature is the root cause of all illness. In: RDA: Rats, Drugs and Assumptions. pp. 199-304. 1995. Life Span Press, Denville, New Jersey.

6. Ali M. Oxygen and Aging. (Ist ed.) 2000. New York, Canary 21 Press. Aging Healthfully Book. p 208

7. Ali M. Spontaneity of Oxidation in Nature and Aging. Monograph, Teaneck, New Jersey, 1983

8. Ali M. Oxygen and Aging. (Ist ed.) 2000. New York, Canary 21 Press. Aging Healthfully Book. pp 76,96

9. Ali M. AA Ali M, Ali O: AA oxidopathy: the core pathogenic mechanism of ischemic heart disease. J Integrative Medicine 1997;1:6-112.

10. Ali M. Oxidative regression to primordial cellular ecology (ORPEC): evidence for the hypothesis and its clinical significance. J Integrative Medicine 1988;2:4-55.

11. Ali M. Oxidative coagulopathy. In: Syllabus of the Capital University of Integrative Medicine, Washington, D.C., 1997.

12. Ali M. Hypothesis: Chronic fatigue is a state of accelerated oxidative molecular injury. J Advancement in Medicine 1993;6:83-96.

13. Ali M. The Canary and Chronic Fatigue. 1994. Life Span Press, Denville, New Jersey.

14. Ali M. Spontaneity of oxidation and molecular basis of environmental illness. In: Syllabus of the 1991 Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1991.

15. Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine 1999;3:11-17.

16. He W, Milao F J-P, Lin D C-H, et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004;429:188-193.

17. Herbert SC. Orphan detectors of metabolism. Nature. 2004;429:143-145.

18. Ali M. Oxygen and Aging. (Ist ed.) 2000. New York, Canary 21 Press. Aging Healthfully Book. pp 208-258.

19. Gould SJ. Natural History. 2000;109;38-47.

20. Bryan Grenfell, Ottar Bjrnstad. Sexually transmitted diseases: Epidemic cycling and immunity. Nature.2005;433:366-367.

21 Grassly NC, Fraser C, Garnett GP. Host immunity and synchronized epidemics of syphilis across the United States. Nature. 2005;433:417-421.

22. Archacki SR, Angheloiu G, Tian XL, et al. Identification of new genes differentially expressed in coronary artery disease by expression profiling. Physiol Genomics. 2003;29:65-74.

23. Greif R, Akça O, Horn E-P, Kurz A, Sessler DI. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med. 2000;342:161-167.

24. Alonso-Echanove J, Richards C, Horan TC. Supplemental Perioperative Oxygen to Reduce Surgical-Wound Infections. N Eng J Med. 2000;342:1613-1614. (Letter to Editor)

25. Lee JT. Supplemental Perioperative Oxygen to Reduce Surgical-Wound Infections. N Eng J Med. 2000;342:1613-1614. (Letter to Editor)

26 Ali M. What is health? The South African of Natural Medicine. 2004;14:14-17.

27 Ali M. Absence of disease is not always presence of health. The South African of Natural Medicine. 2004;14:15.

1. Ali M. The agony and death of a cell. Syllabus of the Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1985.

2. Ali M. Intravenous Nutrient Protocols in Molecular Medicine. Monograph. Institute of Preventive Medicine, Bloomfield, New Jersey, 1987.

3. Ali M. Molecular basis of cell membrane injury. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1990.

4. Ali M. Aging-Oxidant Molecules. The Cortical Monkey and Healing. page 17, 1990. Institute of Preventive Medicine, Bloomfield, New Jersey.

5. Ali M. Spontaneity of oxidation in nature is the root cause of all illness. In: RDA: Rats, Drugs and Assumptions. pp. 199-304. 1995. Life Span Press, Denville, New Jersey.

6. Ali M. Oxygen and Aging. (Ist ed.) 2000. New York, Canary 21 Press. Aging Healthfully Book. p 208

7. Ali M. Spontaneity of Oxidation in Nature and Aging. Monograph, Teaneck, New Jersey, 1983

8. Ali M. Oxygen and Aging. (Ist ed.) 2000. New York, Canary 21 Press. Aging Healthfully Book. pp 76,96

9. Ali M. AA Ali M, Ali O: AA oxidopathy: the core pathogenic mechanism of ischemic heart disease. J Integrative Medicine 1997;1:6-112.

10. Ali M. Oxidative regression to primordial cellular ecology (ORPEC): evidence for the hypothesis and its clinical significance. J Integrative Medicine 1988;2:4-55.

11. Ali M. Oxidative coagulopathy. In: Syllabus of the Capital University of Integrative Medicine, Washington, D.C., 1997.

12. Ali M. Hypothesis: Chronic fatigue is a state of accelerated oxidative molecular injury. J Advancement in Medicine 1993;6:83-96.

13. Ali M. The Canary and Chronic Fatigue. 1994. Life Span Press, Denville, New Jersey.

14. Ali M. Spontaneity of oxidation and molecular basis of environmental illness. In: Syllabus of the 1991 Instruction Course of the American Academy of Environmental Medicine, Denver, Colorado, 1991.

15. Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine 1999;3:11-17.

16. He W, Milao F J-P, Lin D C-H, et al. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004;429:188-193.

17. Herbert SC. Orphan detectors of metabolism. Nature. 2004;429:143-145.

18. Ali M. Oxygen and Aging. (Ist ed.) 2000. New York, Canary 21 Press. Aging Healthfully Book. pp 208-258.

19. Gould SJ. Natural History. 2000;109;38-47.

20. Bryan Grenfell, Ottar Bjrnstad. Sexually transmitted diseases: Epidemic cycling and immunity. Nature.2005;433:366-367.

21 Grassly NC, Fraser C, Garnett GP. Host immunity and synchronized epidemics of syphilis across the United States. Nature. 2005;433:417-421.

22. Archacki SR, Angheloiu G, Tian XL, et al. Identification of new genes differentially expressed in coronary artery disease by expression profiling. Physiol Genomics. 2003;29:65-74.

23. Greif R, Akça O, Horn E-P, Kurz A, Sessler DI. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med. 2000;342:161-167.

24. Alonso-Echanove J, Richards C, Horan TC. Supplemental Perioperative Oxygen to Reduce Surgical-Wound Infections. N Eng J Med. 2000;342:1613-1614. (Letter to Editor)

25. Lee JT. Supplemental Perioperative Oxygen to Reduce Surgical-Wound Infections. N Eng J Med. 2000;342:1613-1614. (Letter to Editor)

26 Ali M. What is health? The South African of Natural Medicine. 2004;14:14-17.

27 Ali M. Absence of disease is not always presence of health. The South African of Natural Medicine. 2004;14:15.

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