Online publication only
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 is primarily one of the
many faces of oxygen homeostasis. In 1990, I devoted a large part
of Oxygen and Aging to this subject.1
Man-microbe conflicts are a legacy of microbe-microbe conflicts
during the primordial period – long before humans appeared
on the scene. Oxygen created and adjudicated microbe-microbe conflicts
then, as it does the man-microbe conflicts now. I came to recognize
this through my clinical work with persons who control microbial
infections well – with or without antimicrobial drugs –
as well as with those who cannot with any antimicrobial. A large
body of personal phase-contrast microscopic and biochemical findings
in those patients led me to the conclusion that the fundamental
molecular derangement in the latter is disruption of the oxygen
homeostasis, including respiratory-to-fermentative shift in ATP
production described previously.2-6
Two Core Concepts
of Crucial Clinical Significance
Below are 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-Béchamp controversy about whether disease is caused
by microbes invading from outside or by microzyma proliferating
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 that this is the
primary factor that leads to massive abuse of antibiotics. In a
chapter titled "Oxygen Settles the Great Pasteur-Béchamp
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, Béchamp's life forms multiplying
from within the body become more important.6
On the surface, the above statement goes against 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 you bring oxygen
into everything?" a patient once asked me. "If you were
designed to run on gasoline, I would bring gasoline into everything,"
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 elaborate and validate the two core
concepts stated above. I do not believe that any of the so-called
mystery maladies – from 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 – from 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 signaling 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;
6. resolution of the Pasteur-Béchamp controversy by oxygen;
7. history of oxygen and the age of dysoxygenosis.
I close this column with brief comments about a disturbing disconnect
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.
In 1983, in "Spontaneity of Oxidation in Nature and Aging,"
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.7
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.
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
alone, I might add for clarity, 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 that any treatment plans for 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 view of 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 statue, 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 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.
Who, I wondered, could have been the role model for Zeus? 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 his wife, Hera,
during his sexual escapades.
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, I wondered, did those clever Greeks create goddess Athena?
In Greek mythology, the benevolent and impetuous supergod Zeus was
created 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 statue 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, infectious,
and degenerative disorders, 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
Medicine 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. (AA oxidopathy
is another way of stating oxidative coagulopathy. The AA initials
refer to Omar Ali and Majid Ali.) 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
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 large body of morphologic observations
(made with high-resolution phase-contrast microscopy) to deal with
the 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 yeastlike 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
of the ORPEC State
The clinical significance of the ORPEC hypothesis is that it provides:
(1) 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) 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.
The ORPEC hypothesis 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
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
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
8. oxidative 3C cascades that contribute to and perpetuate primordial
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 found in individual oxidative
triggers. Rather, the microecologic-genetic shift of the ORPEC state
represents the sum total of cumulative oxidative stressors.
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
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
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. Theoretically,
blockages at various levels in the Krebs cycle can be produced when:
· the cycle enzymes are inactivated
by endogenous and exogenous noxious substances;
· the functions of enzymes are hampered by factors such
as pH, temperature, or changes in the quality and quantity of
· the cycle enzymes are in short supply or imperfectly
produced – enzymes are proteins produced by expression of
genes that encode them;
· the enzyme cofactors are in short supply due to nutritional
· 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
crucially important signaling functions.16,17
6. Oxygen Settles
the Great Pasteur-Béchamp 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 that
microbial species were fixed (monomorphism). Antoine de Béchamp,
his opponent and a prominent microbiologist of the French Academy
of Science, believed that infections are caused by organisms that
develop from within the body and that such organisms undergo radical
changes under different conditions (polymorphism, pleomorphism).
Pasteur and Béchamp showed nothing but disdain for each other's
view. Thus began the great Pasteur-Béchamp debate. Pasteur's
without versus Béchamp's within view of the origin-of-diseases
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 Béchamp's cause
and openly laughed at the blind faith of mainstreamers. To this
day, the Pasteur-Béchamp 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-Béchamp debate is that the
leaders in Béchamp's camp ("Béchampists")
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 Béchampists 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 Béchampists. 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
Béchamp was also right. The core microscopic observations
concerning pleomorphism of Beale, Almquist, Enderlein, and Naessens
are accurate and reproducible, and fully validate Béchamp'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 footnote. Pasteur, the politician,
appropriated to himself much of the prior knowledge of the contagion.
To cite one well-documented example, the Italian scholar-physician
Girolamo Fracastoro (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 the god Apollo is angered
by a shepherd and afflicts him with a new disease.19
of the Oxygen View of the Pasteur-Béchamp Debate
There is an interesting aspect of the great Pasteur-Béchamp
debate which has been brought 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.20,21 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 nonlinearity produced by partial immunity
following the infection – the susceptible-infected-recovered
(SIR) model applies. By contrast, gonococci usually evade postinfection
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 can be divided into the following
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%
of the air; and
3. a period of decreasing concentration of free atmospheric oxygen,
the level falling to 21% 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.
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. 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 policymakers, 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 acute and reversing subacute and chronic disorders.
Even when surgical intervention is needed, as I illustrate in a
latter section of this column, the "oxygen view" has substantial
clinical benefits. Below are two illustrative examples of genetics
of coronary artery disease and oxytherapeutics for surgical procedures
to support the above statements.
and Coronary Heart Disease
Genetic factors are thought to increase the risk of 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, 56 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, subendothelial, 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 that must precede healing. However, ongoing insults lead
to excess production of 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 an irreversibly damaged cell?
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 Journal:
Among the 250 patients who received 80%
oxygen, 13 (5.2%; 95% confidence interval, 2.4 to 8.0%) had surgical-wound
infections, as compared with 28 of the 250 patients given 30% oxygen
(11.2%; 95% confidence interval, 7.3 to 15.1%; P=0.01). The absolute
difference between groups was 6.0% (95% confidence interval, 1.2
to 10.8%). 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
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, they all challenged
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 to blame?
Perhaps those who benefit when safe, effective, and nonpatentable
therapies are suppressed.
The main message of this column is this: the "oxygen view of
immunity and inflammation" offers a unifying model that integrates
diverse and seemingly disparate clinical, biochemical, and genetic
observations concerning immune and inflammatory responses. In integrative
medicine, this model holds that no management plans for immunologic
and inflammatory disorders can be considered complete in which the
fundamental threats to oxygen homeostasis – spiritual disequilibrium
and disruptions of the bowel, blood, and liver ecosystems –
are not addressed.
Majid Ali, MD, is president
of the Institute of Integrative Medicine in New York, NY, and Denville,
NJ. He is the author of the 12-volume series The
Principles and Practice of Integrative Medicine and editor
of the Journal of Integrative Medicine.
Dr. Ali was formerly associate professor of pathology at Columbia
University College of Physicians & Surgeons, New York, NY; president
and professor of medicine, Capital University of Integrative Medicine,
Washington, DC, and president and chief pathologist at Holy Name
Hospital, Teaneck, NJ.
1. Ali M. Oxygen and Aging.
1st ed. New York: Canary 21 Press, Aging Healthfully Books; 2000:208.
2. Ali M. The agony and death of a cell. Syllabus of the Instruction
Course of the American Academy of Environmental Medicine.
Denver, CO; 1985.
3. Ali M. Intravenous nutrient protocols in molecular medicine [monograph].
Institute of Preventive Medicine, Bloomfield, NJ; 1987.
4. Ali M. Molecular basis of cell membrane injury. Syllabus of the
Instruction Course of the American Academy of Environmental Medicine.
Denver, CO; 1990.
5. Ali M. The Cortical Monkey and
Healing, Bloomfield, NJ:
Institute of Preventive Medicine; 1990:17.
6. Ali M. RDA: Rats, Drugs and Assumptions.
Denville, NJ: Life Span Press; 1995:199–304.
7. Ali M. Spontaneity of oxidation in nature and aging [monograph].
Teaneck, NJ; 1983.
8. Ali M. Oxygen and Aging:76,96.
9. Ali M, Ali O. AA oxidopathy: the core pathogenic mechanism of
ischemic heart disease. J Integr
10. Ali M. Oxidative regression to primordial cellular ecology (ORPEC):
evidence for the hypothesis and its clinical significance. J
Integr Med. 1998;2:4–55.
11. Ali M. Oxidative coagulopathy. Syllabus of the Capital University
of Integrative Medicine. Washington, DC; 1997.
12. Ali M. Hypothesis: chronic fatigue is a state of accelerated
oxidative molecular injury. J Adv
13. Ali M. The Canary and Chronic
Fatigue. Denville, NJ: Life
Span Press; 1994.
14. Ali M. Spontaneity of oxidation and molecular basis of environmental
illness. Syllabus of the 1991 Instruction Course of the American
Academy of Environmental Medicine. Denver, CO; 1991.
15. Ali M. Darwin, oxidosis, dysoxygenosis, and integration.
J Integr Med. 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.
17. Herbert SC. Orphan detectors of metabolism. Nature.
18. Ali M. Oxygen and Aging.
19. Gould SJ. Natural History 2000;109;38–47.
20. Bryan Grenfell, Ottar Bjrnstad. Sexually transmitted diseases:
epidemic cycling and immunity. Nature
21. Grassly NC, Fraser C, Garnett GP. Host immunity and synchronized
epidemics of syphilis across the United States. Nature
22. Archacki SR, Angheloiu G, Tian XL, et al. Identification of
new genes differentially expressed in coronary artery disease by
expression profiling. Physiol Genomics
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 [letter]. N
Eng J Med 2000;342:1613–1614.
25. Lee JT. Supplemental perioperative oxygen to reduce surgical-wound
infections [letter]. N Eng J Med
26. Ali M. What is health? S Afr
J Nat Med. 2004;14:14–17.
27. Ali M. Absence of disease is not always presence of health.
S Afr J Nat Med.