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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
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 that 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.2-5.
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 t he
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, butin my viewthe
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, Akηa 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, Akηa 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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