blood oxygenation + ozonation is a protocol that begins with the placement of
two IV catheters. One of these catheters is used to pull blood out of the body,
run it through a dialysis filter, the blood then gets ozonated and infused into
the other catheter in the other arm. As the blood comes out it is typically a
dark color, but after it is filtered and ozonated, it becomes a clean bright
top 3 benefits of EBO2 are as follows:
stimulates a pathway in the body that dramatically decreases inflammation and
even continues to loosen up the inflammation hiding away in the tissues for
some time after the protocol! This inflammation can even be seen as foam in the
waste container. Yes, you'll be able to see the inflammation leaving your body!
This makes the protocol excellent for anyone with an autoimmune disease.
Lowers cholesterol & fat in
○ As the
blood comes out of the body, many times you'll be able to see the yellow globs
of fat leaving the body. These get trapped in the filter and leave your body
for good! Triglycerides and Cholesterol levels can be lowered significantly
with a number of treatments.
Kills Virus, Bacteria, &
has amazing antibacterial, antiviral and anti-fungal properties. To take this a
step further, we use an Ultraviolet light to further impose its antimicrobial
effect. This makes the protocol excellent for patients suffering with Lyme
disease and mold exposure.
We have known for some time that Ozone has some
anti-aging properties. But there are also some other anti-aging aspects of
Medical Ozone therapy that are not readily known. The above diagram
shows some interesting effects of medical ozone. In this particular case the
Ozone was administered intravenously. When Ozone is administered intravenously it
will form two different types of compounds. The first compound is hydrogen
peroxide (H2O2) which helps launch a cascade of reactions
which ultimately reduce inflammation in the body. Less inflammation is less
aging. More to come about this. In the above diagram we see that the Ozone is
reacting with the Poly Unsaturated Fatty Acids (PUFAs) found in the cell
membrane. Poly unsaturated fatty acids all have at least one double bond
linkage between carbon atoms. These double bonds cause them to bend, kind of
like how your arm bends at your elbow. This double bond limits the number of
hydrogen atoms that can bind to the carbon atoms, so the molecule is not as
saturated with hydrogen atoms as it could be. Thus, its considered
unsaturated. Unsaturated fatty acids that have one double bond are called
monounsaturated fatty acids (MUFAs). Unsaturated fatty acids with more than one
double bond are called polyunsaturated fatty acids (PUFAs). Get it? mono for one and poly for many.Polyunsaturated fats can be divided into 2 groups: omega-3s
and omega-6 fats. Two polyunsaturated fatty acids are regarded as essential
because the body cant make them they must come from food. The two essential
fatty acids are alpha linolenic acid (an omega 3 fat) and linoleic acid (an
omega 6 fat). Omega 3 fats, especially those found in seafood, are vital to
help control inflammatory reactions in the body.
POLYUNSATURATED FATS ARE USED AS BUILDING BLOCKS IN THE
MEMBRANES THAT SURROUND ALL THE CELLS OF YOUR BODY AND CONTRIBUTE TO THE
STRUCTURE OF THE BRAIN. The cell membrane seems to be the major area of
reaction between the Ozone and PUFAs.
In the first diagram we see that the Ozone reacts with the
Poly Unsaturated Fatty Acids located in the cell membrane. It forms a compound
called a Lipid Oxidation Products also known as LOPs. These LOPs react with a variety
of cells within the body. In the diagram I have circled in red two important
pathways in the body. These two are the AMPK and mTOR pathways. The effects of
these pathways have profound implications on our longevity. Other important
pathways include: 1. Sirtuin Pathway 2. Nuclear factor-kappa B (NF-kB) pathway 3. NRF2 pathway 4. FOXO pathway. These are very important pathways
especially when it comes to anti-aging and longevity.
Let us take a better look at the AMPK and the mTOR pathways.
The following illustration shows what happens when there is an AMPK deficit:
We are able to see that AMPK deficits lead to many conditions
associated with increased aging. While the opposite is true. Stimulate the AMPK
pathway and you will increase longevity.
The next illustration shows the rewards of increased AMPK:
The metabolic protein AMPK
has been described as a kind of magic bullet for health. Studies in animal
models have shown that compounds that activate the AMPK protein have
health-promoting effects to reverse diabetes, improve cardiovascular health,
treat mitochondrial disease and even extend life span. AMP-activated protein kinase, or AMPK, is known as a
master regulator of metabolism. AMPK deals how our body uses and transforms
is the switch that is the link between metabolic disease, inflammation, and
longevity. This switch tells our cells when to store and generate
energy-containing molecules such as fat, and when to hunker down and use
existing energy store. REMEMBER AMPK ACTIVATION WILL LOWER BLOOD GLUCOSE
LEVELS. THIS IS WHY WHEN SOME PATIENTS RECEIVE AN EBO2 OZONE TREATMENT OR OTHER
IV OZONE TREATMENTS, THEY SOMETIMES BECOME LIGHT HEADED. THEY ACTUALLY HAVE
DROPPED THEIR BLOOD GLUCOSE WHICH CAN EASILY BE REMEDIED BY GIVING THE PATIENT
A SOURCE OF GLUCOSE. THE AMPK PATHWAY HAS DRIVEN THE GLUCOSE INTO THE CELLS.
Thus, in order to further enhance the effects
of the Ozone it is suggested that that the patients follow through with
supplements which further stimulate the AMPK pathway. These supplements
include Resveratrol, Alpha
Lipoic Acid, Gynostemma (a form of Ginseng), Curcumin, Quercetin, and last but
not least is Berberine. These continue to stimulate the
AMPK pathway. The bottom line is the stimulating the AMPK pathway will allow
our bodies to utilize insulin much more efficiently which is a major hallmark
of anti-aging and longevity.
Another important anti-aging pathway is the
mTOR pathway. Actually, the blocking of this pathway is the mechanism
which results in anti-aging. mTOR means Mechanistic Target of Rapamycin.
To slow down aging we want to block most actions of the mTOR pathway. A medication
called Rapamycin will block the action of the mTOR pathway. Interestingly,
Rapamycin can function as an immuno-suppressant. It is used to prevent organ
transplant rejections among other things. When the mTOR pathway is over-activated by nutrients and
insulin, it will act to inhibit insulin signaling, thereby causing insulin
resistance. Insulin resistance is a hallmark of type II diabetes. Higher
insulin levels are associated with increased aging and increased blood glucose.
Acute treatment with Rapamycin abrogates insulin resistance in cells and
animals including humans. One study showed that chronic treatment with Rapamycin
prevented insulin resistance.
There are currently a number of studies that are utilizing
Rapamycin which blocks the mTOR pathway. The mTOR pathway is a master regulator
of cell growth. Think of increased mTOR activity
being an analog of the phrase LIVE FAST, DIE YOUNG, because too much
activity is good for
growth but bad for
lifespan. However, too little mTOR activity
is not beneficial either because it can disrupt healing and insulin sensitivity.
Ozone has an effect on the mTOR pathway mainly by its influence on the AMPK
pathway. AMPK hold the mTOR pathway in check. The following illustration shows
what the mTOR pathway actually influences. Namely, the growth of the cells. mTOR is involved in every aspect of cellular life and existence. In the case of inhibition of mTOR, we are actually trying to apply the brakes to cell growth and proliferation.
In addition, the mTOR pathway is a
direct target of the IGF-1 signaling pathway, which is a major driver of aging. Rapamycin is now available as a treatment modality for
anti-aging. Some supplements which simulate the effects of Rapamycin include
Curcumin, Green Tea Extract, Resveratrol and Pterostilbene, and Fistin. The
next illustration is an example of the mTOR pathway in action. What we see is
that the mTOR pathway is great for cell growth but ultimately it leads to shorter life span, remember, LIVE FAST AND DIE YOUNG. We can see that blocking the mTOR pathway has very beneficial results. It brings on longevity.
Both the AMPK pathway and the inhibition of the
mTOR pathway leads to the process of autophagy. Autophagy
seems to be a crucial component of many longevity protocols. What is autophagy?
humans abandoned their hunter ancestors roaming lifestyle and settled down in
permanent dwellings, they realized the importance and significance of
housekeeping. Ironically, our cells long preceded us to this realization as
they developed their own miniature housekeeping mechanism, known as autophagy
(Greek for self-eating). Autophagy does not only serve as a detoxification tool
but also supports cellular fitness by directing the resulting products from
waste hydrolysis towards energy production and cellular recycling. Mounting evidence indicates that autophagy plays a key
role in aging and aging-related diseases. Enhanced autophagy can delay aging
and prolong life span. The absence of autophagy leads to the accumulation of
mutant and misfolded proteins in the cell, which is the basis for the emergence
and development of neurodegenerative diseases and other aging-related diseases. The following illustration explains
The autophagic activity has
been found to decrease with age, likely
contributing to the accumulation of damaged macromolecules and organelles
during aging. Autophagy is becoming more and more important in the field
of anti-aging medicine.
Another aspect of Ozone Anti-Aging is
the effect that Ozone has on the NQO1 pathway. NQO1 pathway is very important
in the ratio of NAD+/NADH. Ideally, we like this ratio to be about
700/1. NQO1 keeps down the levels of NADH which is thought to be a marker of
aging. Also important about the NQO1 pathway is the influences it holds on P-53
P-53 is called the Tumor Suppressor
Gene. It is very important in dealing with cells that have significant DNA
damage. It will analyze a cell and either fix it or kill it. This is
extremely important for anti-aging. If the damaged cells are allowed to accumulate
they lead to Senescent cells. A Senescent cell is much like a Zombie cell. It
is the living dead. It can cause havoc on our immune system which leads to
aging. The next illustration is a good
example just how the P-53 gene works. It will analyze the cells and determine
their fate. They either survive or perish.
There are also some more well-known
aspects of aging that are associated with Ozone. One aspect includes the anti-aging
aspect that Ozone has upon the Sirtuin pathways via the influence of NAD+
production. Ozone helps produce NAD+ which has significant
implications on the function of the Sirtuin proteins. The Sirtuins are very
important for mitochondrial health. The Sirtuins seem to have an influence on a
number of other aging pathways. For instance, we see here the influences that
Sirtuin One protein has on a number of processes concerned with aging.
Lastly, and just as important, the
effects that Ozone on the NRF2 pathway are very influential in increasing our
longevity. We must remember that NRF2
pathway is a thermostat of anti-inflammation. This dovetails very nicely with a
process the name of which was just coined a few years ago, namely
Inflammaging essentially means that
inflammation leads to aging. This last illustration seems to sum up everything.
Ozone has effects on all these aspects of aging.Thanks, Dr. P
is a gene which controls the production of the enzyme NAD(P)H dehydrogenase, quinone 1. The above diagram shows some
of the many functions of the NQO1 pathway. We can see that there are three
major pillars of health that NQO1 directly influences. These pillars include
detoxification which entails the ratio of NAD to NADH, its ability as an
antioxidant, and lastly how it helps to stabilize the P-53 gene. Detoxification
and antioxidant activity go hand and hand. They are intertwined with each
other. Each of these pillars have extreme importance for our health and
detoxification pillar is a very important aspect of NQO1 functions. Much of the
detoxification deals with compounds called Quinones. Quinonoid compounds
generate reactive oxygen species (ROS). Quinones are ubiquitous in nature and
constitute an important class of naturally occurring compounds found in plants,
fungi and bacteria. Human exposure to quinones therefore occurs via the diet,
but also clinically or via airborne pollutants. For example, the quinones of
hydrocarbons are prevalent as environmental contaminants and provide a major
source of current human exposure to quinones. The inevitable human exposure to
quinones, and the inherent reactivity of quinones, has stimulated substantial
research on the chemistry and toxicology of these compounds. NQO1 is employed
in the removal of a quinone from biological systems as a detoxification
reaction: NAD(P)H + a quinone → NAD(P)+ + a hydroquinone.
The hydroquinone is excreted. This reaction ensures complete oxidation of the
substrate without the formation of semiquinones and reactive oxygen radicals
that are deleterious to cells. The localization of NQO1 in epithelial and
endothelial tissues of mice, rats and humans indicates their importance as
detoxifying agents, since their location facilitates exposure to compounds
entering the body. In addition to the detoxification, NQO1 helps produce NAD+
which in its own right is very important.
ratio of NAD+/NADH is of extreme importance. We are well aware of
the importance of NAD+ for our body. NAD+ is instrumental
in the production of ATP which is the body’s energy currency. However, NAD+
is also used in a variety of biological processes in the body. Nicotinamide
adenine dinucleotide (NAD+) is an essential pyridine nucleotide that
serves as an essential cofactor and substrate for a number of critical cellular
processes involved in oxidative phosphorylation and ATP production, DNA repair,
epigenetically modulated gene expression, intracellular calcium signaling, and
immunological functions. NAD+depletion
may occur in response to excessive DNA damage due to free radicals. This damage
results in significant poly (ADP-ribose) polymerase (PARP) activation and a
high turnover and subsequent depletion of NAD+. PARP is instrumental
in DNA repair. Also, chronic immune activation and inflammatory cytokine
production results in accelerated CD38 activity and subsequent decline in NAD+ levels.
now think that the NAD+/NADH ratio may be as important if not more
important than the levels of NAD+. One of the insights arising from
the scientific studies of calorie restriction is that the ratio of NAD+ to
NADH (NAD+/NADH ratio) might be important for the lifespan extension
benefits. This ratio has been reported to decline with age, with NAD+ being
decreased and NADH increased in older individuals. While boosting the amount
of NAD+ has been getting a lot of attention, improving the
ratio between NAD+ and NADH might be more significant than the
amount of cellular NAD+ in isolation. In yeast experiments,
calorie restriction decreases NADH much more dramatically than it affects NAD+.
This decrease in NADH is important for enhancing lifespan, because, on its own,
it increases activity of the NAD+ consuming enzymes that boost
longevity processes (e.g., Sirtuins) and DNA repair (e.g. PARPs) in yeast. This
is thought to occur because NADH is an inhibitor of these enzymes, so lowering
it releases the inhibition. As an example, inducing the enzyme NQO1—an enzyme
that uses NADH as an electron donor increases intracellular NAD+ levels
because it shifts the NAD+/NADH redox ratio in favor of oxidation
(NAD+). A side effect of this reaction is that intracellular NAD+
levels increase. Upregulation of the pathway that induces NQO1 occurs in
calorie restriction and appears to be an important component of producing the benefits.
We must remember that cellular levels of NAD+ are more important
than the serum levels.
review, what NQO1 does is convert NADH to NAD+ while at the same
time it maintains a very delicate ratio of NAD/NADH. This ratio is not affected
by dietary or IV intake. One important fact is that NQO1 will oxidize NADH to
NAD+ and thus it increases NAD+ in the cell.
HOW IS THE NQO1 PATHWAY REGULATED?
Another name for the NQO1 gene is the longevity
gene. NQO1, regulates the NAD+/NADH
ratio in cells. NQO1 does this by oxidizing NADH to NAD+.
During aging the ratio of NAD+ to NADH changes in part to a reduced
level of the expression of NQO1. As we age the cells accumulate a type of
protein called BET proteins. The BET proteins are Bromodomain and Extraterminal
Proteins. They are referred to as epigenetic readers. The following diagram
shows the various components involved in epigenetics, namely the writers,
erasers, and readers all of which effect gene behavior.
this case, the BET proteins will suppress the induction of the NQO1 gene. There
is now much research looking for inhibitors of BET proteins for a variety of
conditions including cancer.
levels of NQO1 will affect the amounts of a compound called Peroxisome
proliferator-activated receptor-gamma coactivator (PGC-1alpha). PGC-1a is a
member of a family of transcription coactivators that plays a central role in
the regulation of cellular energy metabolism. It is strongly induced by cold
exposure, linking this environmental stimulus to adaptive thermogenesis.
PGC-1alpha stimulates mitochondrial biogenesis and promotes the remodeling of
muscle tissue to a fiber-type composition that is metabolically more oxidative
and less glycolytic in nature, and it participates in the regulation of both
carbohydrate and lipid metabolism. Oxidative metabolism produces far more ATP
than the glycolytic type. It is highly likely that PGC-1alpha is intimately
involved in disorders such as obesity, diabetes, and cardiomyopathy. In
particular, its regulatory function in lipid metabolism makes it an inviting
target for pharmacological intervention in the treatment of obesity and Type 2
is regulated by the oxidative state of the cell. NQO1 will regulate the PGC-1a
levels by controlling the rate of PGC-1a degradation not its synthesis. Like many
regulatory factors, PGC-1a has an extremely short half-life. All of these
extremely short-lived proteins are regulated by degradation rates, not
synthesis rates. Higher levels of NQO1 shift the ratio of NAD+/NADH
and protect proteins from being oxidized. PGC-1 plays an important role in
regulating mitochondrial function. Higher levels of PGC-1a help prevent age
related mitochondrial dysfunction. Thus,
it appears that under conditions of oxidative stress, such as with aging,
NQO1 may be a major factor that controls the concentration of
PGC-1a in the cell. PGC-1a is not some esoteric co factor, it is
extremely important in many different functions as can be seen from the
following diagram. PGC-1α is a transcriptional coactivator that is a central
inducer of mitochondrial biogenesis in cells.
Thus, it appears that under conditions of oxidative
stress, such as with aging, NQO1 may be a major factor that controls
the concentration of PGC-1a in the cell.
ELSE DOES NQO1 STIMULATE?
seems to have a significant effect on the P-53 gene. It helps to stabilize the
P-53 gene. P-53 is many times referred to an the “Tumor Suppressor Gene”. It is
a potent sentinel in the body looking for and destroying cells which may go on
to tumor lines. It has the ability to fix DNA damage if it is not too severe or
if too severe it will destroy the cell. The following diagram shows P-53 in
is now thought that many cancers arise from a defect in the P-53 gene. It
appears that the NQO1-dependent (ubiquitin-independent) pathway is the most
important pathway for regulating p53 levels within the cell. Ubiquitin is a
small protein that is found in almost all cellular tissues in humans and other
organisms. It helps to regulate the processes of other proteins in the body.
Through a process known as ubiquitination or ubiquitylation, a ubiquitin
molecule can bind to a substrate protein, changing the way it functions. This
can lead to a number of different outcomes. It is most widely recognized for
its role in apoptosis of proteins, earning it the title of the molecular “kiss
of death” for proteins, although it also plays a major part in several other
cellular processes related to the regulation of proteins. If P-53 is working
properly hopefully the chances of a cancer arising are significantly
diminished. Treatment with curcumin augments the levels of P53 in tumor cell
lines through incrementing its half-life in a NQO1 dependent manner. Curcumin
treatment promotes the interaction between NQO1-p53.
CAN WE INCREASE THE PRESENCE OF NQO1?
statement that can be made across the board is that anything which increases
the NRf2 pathway will increase the NQO1 gene action. The NRf2 pathway has a
profound effect on the NQO1 gene. One can read my previous blogs concerning the
NRf2 pathway. I call this pathway the thermostat of anti-inflammation. One of
the important stimulators of the NRf2 pathway are ozone messengers which are
produced by intravenous ozone such as is delivered by the EBO2 protocol. These
messengers will allow the NRf2 to enter the nucleus and activate certain genes.
Another offshoot of the EBO2 protocol is the use of photodynamic therapy which
stimulated the NQO1 gene. Phototherapy also includes the stimulation of heat
shock proteins which are encouraged by the exposure of UVA light.
for those people unaware of the EBO2 protocol, it is a protocol which uses a
dialysis filter, intravenous Ozone gas, and photo modulation. The following is
a picture of the set up used in the EBO2 protocol:
compounds which seem to have stimulating influences on NQO1 include
resveratrol, Pterostilbene, Taxifolin (also called dihydroquercetin), sulforaphane (broccoli), curcumin, and
Fumaric acid derivatives.
important supplement perhaps the most important, to stimulate the NQO1 gene is Beta-lapachone, a compound found in
the bark of the South American Lapacho tree. It is a potent activator of the NQO1
gene and produces ROS in cancer cells, but reduces ROS in non-cancer
cells. Beta-Lapachone is a NQO1
activator. In addition to stimulating the NQO1 gene it stimulates the NRf2
pathway which helps to lower inflammation. Beta-lapacho was very popular a
number of years ago. It then seemed to lose it way. Now there is a resurgence
in the use of Beta-lapachone on multiple fronts including clinical studies in a
variety of universities. A few final thoughts, if a clinic is utilizing NAD+
but not stimulating the NQO1 pathway then they are behind the times. There are
a number of clinics which like to dabble in utilizing NAD on their patients. Unfortunately,
they are not aware of the basic science of NAD, its effect on senescent cells,
methods allowing the body to handle NAD better, and the importance of the NQO1
gene. If you encounter a clinic which is “just” utilizing NAD without
addressing these related matters, your best bet is to seek treatment
elsewhere!! This will ensure you the best chance of success. It is all a matter
of knowing the basic science of the various pathways and how these can be
manipulated to the benefit of the patient.
following illustration gives all the salient points about the NQO1 gene. There
is a reason why this is called the Longevity Gene. The answers lie in the
illustration. When all is said and done this seems to represent the essence of