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.
Yes, you read that right.
An exciting form of advanced physical
therapy called Blood Flow Restriction Therapy (BFR) has proven to be especially
useful after a regenerative cell procedure to strengthen the muscles around an
The way it works is quite simple: after partially
restricting blood flow using a series of well-calibrated, inflatable Velcro
bands (tourniquets), patients perform muscle contractions to increase the size,
strength and endurance of healing muscles.
Its like lifting weights, but with tight
cuffs on your arms or legs.
Heres what you need to know:
BFR training can be performed 2-3 times a week for three weeks OR 1-2
times a day for less than three weeks
A good ratio for upper body and lower body is 40% arms to 50% legs (or
BFR is best used with four reps per set, in the following sequence:
Maximum wear time for the cuffs is 20 minutes
The ideal loads will be 20% to 50% of a patients one rep maximum lift
Repetitions should be slow, up to two full seconds for each positive and
Rest should be anywhere from 30 to 60 seconds between sets.
BLOOD FLOW RESTRICTION THERAPY (BFRT) IS AN INNOVATIVE
TRAINING METHOD FOR THE DEVELOPMENT OF MUSCLE STRENGTH AND HYPERTROPHY
Institute is always on the prowl to find new regenerative technologies. More
importantly, we are looking to combine these new technologies to add to our
uniqueness. One newer technique that we are looking at is Blood Flow
Restriction Therapy (BFRT). Blood flow restriction is becoming a new
modality in the world of Regenerative Medicine, Sports Medicine, and
performance enhancement. It is one of the hottest trends
in this years Tokyo Olympics. Actually, it has been around for a while.
In professional sports circles, BFRT is
becoming more and more accepted. The initial appeal for BFRT training was driven by studies demonstrating
rapid increases in muscle size, strength, and endurance capacity, even when
notably low intensities and resistances, which would typically be incapable of
stimulating change in healthy populations, were used. The incorporation of BFRT
exercise into the training of strength- and endurance-trained athletes has
recently been shown to provide additive training effects that augment skeletal
muscle and cardiovascular adaptations.
The above illustration shows the main
tools for blood flow restriction, namely a series of tourniquets that are used
during exercises. As we can see, the equipment is not extremely expensive or
flow restriction is a training method partially restricting arterial inflow and
fully restricting venous outflow in working musculature during exercise. This
technique seems to have originated in Japan by Dr. Sato in 1966. This technique
is called Kaatsu training which translates to training with pressure. The manipulation of blood flow in conjunction with skeletal
muscle contraction has helped us with the physiological understanding of muscle
fatigue, blood pressure reflexes, and metabolism in humans. BFRT and KAATSU
training differ by only modifying blood flow rather than stopping it. KAATSU
training uses expensive pneumatic tubes, cuffs and electronic monitors and
requires a certified specialist to monitor you during your workout. Blood
flow restriction solutions, such on the other hand, are simple to use and can
easily be added to your workouts to maximize results. BFRT training
allows you to adjust the pressure of the bands or straps
yourself. However, it is still not recommended that one attempts this
treatment on their own without first getting some guidance from a certified
The following illustration is an overall synopsis of
how to administer Blood Flow Restriction Therapy. I still recommend that this
not be attempted on your own. One needs instruction in this technique. This is
the practical aspect on how to do this therapy but the real question is how
does it work?
THE PROPOSED METHODS AS TO HOW BLOOD FLOW
RESTRICTION THERAPY (BFRT) WORKS
Recent interest in using intentional blood flow
restriction has focused on elucidating how exercise during periods of reduced
blood flow affects typical training adaptations.
The initial appeal for BFR training (BFRT)
was driven by studies demonstrating rapid increases in muscle size, strength,
and endurance capacity, even when notably low intensities and resistances were
utilized. These levels would typically be incapable of stimulating change in
healthy populations. The incorporation of BFRT exercise into the training of
strength- and endurance-trained athletes has recently been shown to provide
additive training effects that augment skeletal muscle and cardiovascular
adaptation. It has been
generally accepted that muscle hypertrophy requires high-intensity training
utilizing loads of at least 70% of 1-repetition max or lower loads until
failure. However, there is mounting evidence that now supports
low-load resistance training (20-40%RM) combined with blood flow restriction
can similarly induce muscle hypertrophy and strength gains. What we thought we knew and
understood about muscle cell physiology and hypertrophy has been
turned upside down through blood flow restriction research.
alters acute physiological stressors such as local muscle oxygen availability
and vascular shear stress which may lead to adaptations that are not easily
attained with conventional training. The above diagram is a good synopsis of
the various changes that occur with BFRT. We can see that there are three
categories, high intensity, low intensity with BFRT, and low intensity. There
are many similarities between high intensity and low intensity with BFRT. One
interesting fact is that the low intensity with blood flow restriction seems to
cause little muscle damage meaning that the recovery time is much quicker.
Also, there are significant increases in growth hormone, IGF-1, and mTOR in the
low intensity exercises with BFRT.
Actually, these increases outstrip those of high intensity training.
BFRT seems to be
a myostatin blocker. It will down regulate myostatin. Myostatin blockers are a holy grail for body
builders. Myostatin is a protein that blocks muscle cell growth and
differentiation. When you use BFRT, you get this unlocking ability to get more
muscle cell growth with minimal exercise load. Below we see a picture of a
steer who was born with genetic mutation which resulted as if a myostatin
blocker were utilized.
currently a great deal of research concerning myostatin blockers. A number of
compounds are currently being studied but there is still no truly effective
MORE ABOUT THE
BIOCHEMISTRY AND PHYSIOLOGY OF BFRT
The above illustration gives a better idea
of the aspects of the biochemistry/physiology involved with BFRT. We have already discussed the fact that
myostatin is blocked. In this diagram, we see there is formation of heat shock
proteins. Heat shock proteins normally are stimulated by subjecting the body to
heat or cold. However, other stresses, such as BFRT, can also stimulate their
production. There are a number of different types of heat shock proteins. Heat
shock proteins are important in that they help proteins fold properly into the
cells. Many degenerative diseases including Alzheimers are associated with
misfolded proteins. The following illustration shows the benefits of heat shock
proteins. They rescue damaged proteins and fix them which will hopefully slow
down aging and diseases.
Another important aspect of BFRT is the
generation of Nitric Oxide (NO). Nitric oxide is considered a signaling
molecule in the body. It has implications in many different biological systems
in the body. In the context of BFRT, the NO will have direct effect on muscle
growth. It will also stimulate the blood vessels and cause them to dilate
eventually increasing the blood supply. The illustration below gives us an idea
of the importance of the Nitric Oxide molecule. In our clinic, we recommend the
use of supplemental Nitric Oxide stimulators. By far the best one out there is
Another regulator of growth to consider is
called the mTOR pathway. The mTOR
pathway integrates the input from upstream pathways which are dependent upon insulin and other growth factors such as IGF-1 and amino acids. The mTOR pathway also
senses cellular nutrient, oxygen, and energy levels. It is a very important
pathway when it comes to cellular growth. One must realize that the m TOR
pathway is both good and bad. In some instances, stimulation of the m TOR
pathway may speed up aging. In controlled circumstances, mTOR pathway may be
beneficial. It will definitely contribute to cellular growth. But this can be a
double-edged sword. We must remember that when we are concerned with anti-aging
we wish to block this pathway with the mTOR inhibitors. Cellular growth speeds
WHAT IS THE PHYSIOLOGY INVOLVED IN BFRT?
Many of the findings of BFRT reinforce the
findings of the Nobel Prize in Physiology 2019 which describes how varying
levels of oxygen shape both physiology and pathology in the body.
In the case of BFRT, muscles are exercised
to fatigue in an environment that prevents (temporarily) the flushing out of
metabolites, and thus providing a metabolic environment more prone to stress
signaling, low oxygen etc. There are a variety of physiological mechanisms
thought to provoke a hypertrophic response in skeletal muscle following BFRT.
Although the exact mechanisms of BFRT are not completely known, most evidence
alludes to a muscle cell swelling response and an indirect effect of
metabolites. This will instigate an increased muscle activation through
fatigue. Regardless of the initial signaling mechanism, the intracellular
environment should favor a positive protein balance for muscle growth achieved
by an increase in muscle protein synthesis, a decrease in muscle protein
breakdown, or both.
The proposed mechanisms of occlusion in
BFRT indicate there are increases in blood lactic acid levels and alterations
in blood pH similar to High Intensity Training. Lactate is typically a waste
product produced by muscle metabolism in low oxygen situations. The increased
lactic acid will stimulate increases in serum growth hormone which in turn
promotes collagen synthesis for tissue repair and recovery. Ultimately, this
results in muscle satellite stem cell proliferation. Skeletal muscle satellite cells are considered to
play a crucial role in muscle fiber maintenance, repair and
remodeling. Satellite cells
are precursors to skeletal muscle cells. They are essentially a muscle stem
cell. They have the potential to provide additional myonuclei to their parent
muscle fiber, or return to a quiescent state. In response to mechanical strain,
satellite cells become activated and produce muscle. BFRT will increase the
number and activity of satellite cells.
In the above schematic of the muscle stem
cells, BFRT increases the number of satellite stem cells thus increasing the
number of muscle fibers. The following illustration demonstrates the various
conditions which diminish muscle fiber generation. These conditions, such as
diabetes, obesity, etc. can be benefited by BFRT.
technique of BFRT in the muscle using a pneumatic tourniquet system involves
applying an external pressure, typically using a tourniquet cuff, to the most
proximal region of the upper and/or lower limbs. When the cuff is inflated,
there is gradual mechanical compression of the vasculature underneath the cuff,
resulting in partial restriction of arterial blood flow to structures distal to
the cuff, but which more severely affects venous outflow from under the cuff
that is proposed to also impede venous return. Compression of the vasculature
proximal to the skeletal muscle results in inadequate oxygen supply (hypoxia)
within the muscle tissue. Furthermore, the diminution of venous blood flow
results in blood pooling within the capillaries of the occluded limbs, often
reflected by visible erythema. For safety purposes, its
important to understand were not cutting off blood flow all together for
extended periods of time, which is foolishly dangerous. For the most part,
were applying heavy circumferential compression. This is the reason why one
should not experiment on ones self. The following is a good synopsis of BFRT:
As of now I am not aware of any
restrictions from professional leagues or the World Anti-Doping Agency
concerning BFRT. There is little if any doubt that this technique will improve
There is no doubt about the validity of
BFRT and how it will benefit and change the practice of Regenerative Medicine
and performance enhancement. As time goes on, it will have even more influence
as it is combined with other modalities. We will start utilizing this therapy
and will hopefully make it an intrical part of our new state of the art
facility which we expect to move into early next year. What will make this more
unique is that we will combine BFRT with other modalities such as Hyperbaric
Oxygen, Ozone Therapy (EBO2), Xenon Therapy and a few other modalities. Our new
facility will be a one stop state of the art facility like nothing else around.
We have recently obtained another key weapon in our
office. This weapon is a true Class 4 COLD LASER. But this is not like the
typical class 4 laser. Many people know about lasers but are not exactly sure
how they achieve their goals. The basic science of lasers is that they use the
principle of Photobiomodulation. The following illustration shows this concept.
Photobiomodulation is defined as a form of
light therapy that utilizes non-ionizing light sources. These include near ultraviolet, visible light, infrared, microwave, radio waves,
and low-frequency radio frequency (long-wave) are all examples of non-ionizing radiation. By contrast, far
ultraviolet light, X-rays, gamma-rays, and all particle radiation from
radioactive decay are ionizing
light sources. Photobiomodulation is a NON-THERMAL process involving endogenous
chromophores. The first law of photobiology
explains that for a low power visible light to have any effect on a living
biological system, the photons must be absorbed by electronic absorption bands
belonging to some molecular photo-acceptors, which are called chromophores.
Here is a good explanation of chromophores.
A chromophore is the part of a molecule
responsible for its color. The color that is seen by our eyes is the one not
absorbed by the reflecting object within a certain wavelength spectrum of
visible light hence the objects steal the objects from the wheel. Chromophores will elicit reactions at various biological sites. This process
results in beneficial therapeutic outcomes including but not limited to the
alleviation of pain or inflammation, immunomodulation, and promotion of wound
healing and tissue regeneration. We can see this principle in
the following illustration:
What we are able to see is that a very
important aspect of laser therapy involves the mitochondria. The mitochondria
produce ATP which is the body's energy currency. It does this by stimulating
the Cytochrome C Oxidase which is an enzyme in the electron transport chain of
the Krebs cycle. Laser therapy produces a
shift in overall cell redox potential in the direction of greater oxidation and increased Reactive Oxygen Species
(ROS) generation. In a biological
context, ROS are formed as a natural byproduct of the normal aerobic metabolism
of oxygen and have important roles in cell signaling and homeostasis. ROS are well known to stimulate
cellular proliferation of low levels, but inhibit proliferation and kill cells
at high levels. Nitric oxide is also involved in laser therapy. It may be
photo-released from its binding sites in the respiratory chain and elsewhere.
Nitric oxide will increase vasodilation and thus increasing blood supply.
Nitric oxide may also act as a neurotransmitter helping with pain control. Also,
not to be overlooked is the fact that the mitochondria have many important
tasks in many other aspects of cell biology and cell signaling pathways.
It has been proposed that
the redox state of a cell regulates cellular signaling pathways that control
gene expression. Modulation of the cellular redox state can activate or inhibit
signaling pathways. When we start affecting the various pathways and affecting
gene expression we have now crossed into the field of Epigenetics. Several
regulation pathways are mediated through the cellular redox state. Changes in
redox state induce the activation of numerous intracellular signaling pathways,
such as nucleic acid synthesis, protein synthesis, enzyme activation and cell
When all is said and done the application of a
therapeutic dose of light to impaired or dysfunctional
tissue leads to a cellular response mediated by mitochondrial mechanisms that
reduce pain and inflammation, speed healing, and cell hemostasis. These cellular mechanisms responsible for the effect of
visible light on cells include cytochrome c oxidase. Mitochondria are thought
to be a likely site for the initial effects of light, leading to increased ATP
production, modulation of reactive oxygen species, induction of transcription
factors, and possible changes in mitochondrial DNA. These effects in turn lead
to increased cell proliferation and migration particularly by fibroblasts.
Fibroblasts are responsible for the production of collagen which is a basic
building block for many of the bodys tissues including bone, cartilage etc. The
lasers overall effect is that it will
bio stimulate cells to increase cellular growth and regenerative activity,
while simultaneously deactivating 7 or the 9 enzymes that cause inflammation by
up to 70%.
Another unique aspect of lasers is that they are considered to be monochromatic,
coherent and collimated. Monochromatic means that there is a single wavelength
which stimulates particular human tissues that will only respond to that
specific wavelength being utilized. Coherent means that it minimizes the photon
scatter as light interacts with the tissue. Lastly, because lasers have a
higher power that works with a specific wavelength, they are collimated which
allows it to actually reach the deep tissues. The following illustration drives
home these points.
ARE LASERS CLASSIFIED?
One may ask how are the lasers classified? The FDA classifies lasers from I to IV. For instance, a Class IV Laser is any laser
device that the FDA has determined is powerful enough to pose a significant
risk of injury to the eye. Consequently, being Class IV does not necessarily
laser more effective, as that would depend upon
what you intend to do with it and how you use it. Some Class IV lasers are used
in health and medical settings for a wide range of therapeutic applications.
Others are used for construction, cutting, burning and by hobbyists such as
high-powered laser pointers.
Let us look at some further
perimeters of the Class IV Lasers. Hot lasers are known as Class IV lasers. Class IV lasers
have a power output above 500 milliwatts (mW). At a lower power range, hot
lasers are used for therapeutic purposes. Class IV lasers can cut tissue during
surgical procedures. Most Class IV lasers are called hot lasers because they
can rapidly increase tissue temperatures. The one common tread with class IV
lasers is that they have higher power outputs and most translate the energy to
On the other hand, most, cold lasers are also known
as low-level lasers, they are among Class II and Class III lasers. Cold lasers
have a power output of less than 500 mW. These lasers are called cold because
they do not generate a thermal effect. But we must realize that the decreased
power will also decrease the penetration depth of the laser. The vast majority
of lasers in medical use are not true class IV cold lasers but class III
lasers. Many of them are advertised as a Class IV lasers but in reality, they
are Class III lasers. If they happen to a Class IV laser then most of the
energy is expended as heat. They may have some bells and whistles and other
gimmicks. But it does not make them any more effective. As we can see in the
following illustration, typically a Class IV laser will need much less
treatment time than a Class III laser. Also, we will obtain a much greater
depth of penetration with the Class IV laser. What most medical professionals
do not seem to understand is that a laser with many medical benefits produces
it benefits with LIGHT ENERGY NOT HEAT. Thus, when one is looking to
derive benefits from the laser, heat should not be a consideration. THE
PHOTONIC ENERGY IS WHAT ONE NEEDS TO BE CONCERNED ABOUT. The following
illustration will give an idea about the difference. The most significant
difference in the various types of lasers is the depth of penetration.
There is a misunderstanding
that a more efficient laser will produce heat.
This is simply not the case. Most of the time when we are utilizing a laser we
are interested in the depth of penetration. We also do not wish to subject the
patient to long hours of treatment. So, if we can eliminate the heat and get
penetration of depth than we may have something special. When all is said and
done IT IS THE PHOTONIC ENERGY WHICH ACCOMPLISHES THE REPAIR.
WHAT WOULD BE MY CHOICE FOR AN OPTIMAL LASER?
I have used lasers for many years. The use of lasers
for musculoskeletal conditions has long passed the point of being experimental.
There are many different types of lasers in use. In our clinic we have been
very happy with our laser sleeves and our original hand-held Class IV type
laser. The original Class IV laser which we have been using requires eyewear
protection and it will produce heat which could burn the skin. Nevertheless, it
was efficient but at the same time there was a risk of thermal injury and
because of the thermal considerations I believe the penetration was limited.
If I were able to design a laser I would want one to
be a Class IV laser that essentially did not cause any thermal damage. To be
effective, the laser would have to have a power output of greater than 500
milliwatts. It would need to be monochromatic and have a wavelength of
approximately 680 mM which is the ideal wavelength to stimulate the
mitochondria. This is the sweet spot in the red spectrum range.
It obviously requires eyewear. Also, it is cold laser. What are the differences
between and hot and cold laser? Again, Cold Lasers are therapeutic
lasers that produce an insignificant amount of heat and are extremely safe for
use by professionals.
us take a look at the specs of the new laser. The output of the new laser is
750 milliwatts. Remember, the energy output for the Class IV laser is above 500
milliwatts. So, we definitely classify as a Class IV laser by power output. The
new laser is monochromatic so it essentially stays on one wavelength and its
wavelength is 680 nM which is the sweet spot for mitochondrial stimulation etc. The
wavelength is 680 nm. This is the sweet spot in the red spectrum range. This
provides both a large safety margin and potent force. If
we were to lower the wavelength we could lower the safety margin. The last
aspect to an ideal laser is what is called lumen intensity. We need to look at
some physical aspects of light when looking at lumen intensity. There are three
terms we want to know when assessing lumen intensity. These are lumens, lux and
candela. A good way to remember the differences
between terms is:
are how much light is given off
how bright your surface will be
measures the visible intensity from the light source.
The lumen intensity of the new laser is 550 lumens per millimeter
of tissue radiated. The beam profile is one millimeter. This last spec will
allow the user to pinpoint targeting tissue. Example would be a meniscus tear
located posteriorly in the medial compartment, or a tear in the supraspinatus
located inferior to the acromion for example. This later spec you can only
utilize the function of when the laser is a true class four. You need the power
of penetration without the heat damaging aspect. This is a very important aspect
and the one important principle which needs to be conveyed and understood - not
easy to do! True photonic intervention is dependent on absorption of the light
force or energy. Not in the heat transmission normally incorporated into laser
modules. The light is the energy! Again, we see a picture of our new Class IV
laser. Notice it is a hand-held laser. It is battery powered. Many times,
simplicity is a goal strived for but many times seldom achieved.
The next illustration is a summation of all the
benefits our new Class IV laser is able to achieve while at the same time being
extremely safe to the patient as long as the proper eye precautions are taken. The
last two illustrations are videos comparing the new class IV cold laser with a
typical Class IV laser. The differences between the two are remarkable.
The last two items really drive home the point of what
makes this Class IV cold laser a truly unique laser. They are pictures and
videos on two types of Class IV lasers. One is a typical Class IV laser which
most medical professionals are familiar with. The other is the new Class IV
cold laser. I did an experiment with two Class IV lasers. The first
illustration is the typical Class IV laser. Now the wattage used with this
laser is in the 6-watt range. This would probably cause a burn to the skin at
this power especially if it were kept in the same spot. On the other hand, the
second image is the true Class IV cold laser. Notice the difference in light
I suspect this new Class IV cold laser may be a game
changer. The preliminary results in the office are quite impressive. We are
truly making use of photonic energy to make a difference. Time will tell, but
this seems to be exactly what we asked for.
Below is the Class IV hot laser shined into a container having a mixture and saline. We can see the red color from the laser is not vibrant. Realize that when the laser is being used on the body it will need to penetrate a mixture of saline and blood.
The next picture and video are of the new Class IV cold laser. Notice how vibrant the color is. The same will happen in your body. Realize that the only difference between these pictures is the lasers. The container is the same container.
This is an especially fascinating study as far as
aging is concerned. I left the article link at the end of my write up. What
this study looked at was the ability of long-lived people to repair DNA damage.
In this particular case they looked at inherited
and naturally occurring genetic changes in older people. They found in the
long-lived population two particular genes COA1 and STK17A. These are rather
esoteric names but the importance is there! COA1 is involved with energy
production and communication between the mitochondria and the cell nucleus.
COA1 performed three functions that are part of the blue prints for anti-aging
platforms. They directed cell response to DNA damage, they prompted badly
damaged cells to die off, and controlled the amounts of Reactive Oxygen
Species. I suspect these genes are stimulating the P-53 gene. P -53 is called
the tumor suppressor gene. Taking things one step further, remember that NAD+ is a substrate for DNA
repair proteins such as PARP1, PARP2 and PARP3 as well as
enzymes that can influence DNA
repair capacity such as SIRT1 and SIRT6. The PARP enzymes
typically get shut off when the body does not have enough NAD+ to go
around. Looks like there may be some
overlap here. Activate the DNA repair genes and you may live longer. At least
you are giving yourself better odds. This is why I feel it is of paramount
importance to take NAD supplements both orally and intravenously. Also remember,
there is much science out there that shows Ozone therapy can increase the NAD
levels in the body in addition to dramatically decreasing damage from Reactive
Oxygen Species. The moral of the story here is:
MAKE SURE YOU TAKE YOUR NAD TO
STAY YOUNG.Here is the article I am talking about:https://bigthink.com/surprising-science/semi-supercentenarians-dna-repairThanks,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
The above was a recent headline. I know what my political persuasions are, and they should obviously never get in the way of science or the health of a patient. Furthermore, I always try to be non-political in my posts. I see that some members of the press have tried to ridicule President Trump for an idea of “getting light inside the body.” Here are the quotes attributed to the President: “Suppose that we hit the body with a tremendous, whether it’s ultraviolet or just very powerful light,” Trump said at the White House coronavirus press briefing, adding: “Supposing you brought the light inside the body, which you can do either through the skin or in some other way.” Well, low and behold, if reporters find this a ridiculous statement, then they need to do their homework and learn some science, and have a more analytical mind.I would like to mention a paper that was published a few years ago by Dr. Michael Hamblin. Michael Hamblin is a Principal Investigator at the Wellman Center for Photomedicine (see below) at Massachusetts General Hospital, an Associate Professor of Dermatology at Harvard Medical School and a member of the Affiliated Faculty of Harvard-MIT Division of Health Science and Technology.The next insert is a copy of the title page of a paper written and published by Dr. Hamblin in 2017.We can see that the title of the article is Ultraviolet Irradiation of Blood: “The Cure that Time Forget”. As one can see we have a PHD from Harvard and MIT who is a main principle investigator at Harvard’s photomedicine center state that ultraviolet light to the blood is a cure that time forget. So, it seems that that President was not off the mark at all. I think he is owed an apology by those in the media and in the medical community who ridiculed him. I have been fortunate to meet Dr. Hamblin when we were both lecturing at a regenerative medicine meeting. I consider him one of the world’s experts on photo-therapy. I read the above article a few years ago and found it intriguing. There are many similar articles. In this article there is a discussion of the potential of Ultraviolet Blood Irradiation (UBI) as an alternative approach to current methods used to treat infections. It goes on to say that this therapy can also be an immune-modulating therapy and also as a method for normalizing blood parameters. The article states there is no resistance of microorganisms to UV irradiation. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. Ultraviolet light when used for sterilization purposes causes the direct destruction of pathogens. Many people believe that this is also the mechanism of action for UBI which is absolutely not the case. It is the stimulation of the immune system and its various components that gives ultraviolet light therapy is effectiveness in addition to destroying the micro-organisms.The following diagram is from the article by Dr. Hamblin. It shows some of the various aspects of UBI on the immune system. This may be a complicated picture but when all is said and done it is stimulating the immune system in many different ways. It is somewhat complicated to the lay person.UBI appears to have three broadly different classes of effects on different blood components. In the case of various white blood cells which are called neutrophils, monocytes, macrophages, and dendritic cells. UBI can activate phagocytosis. Phagocytosis is a process wherein a cell, in this case a type of white blood cell, binds to a microbe such as a bacteria or virus and engulfs it. UBI also increases the secretion of Nitric Oxide which stimulates the production of cells which can calm down an inflammatory reaction. By reducing the inflammatory response, we are lessening the effects of a “cytokine storm” as is often found in infections and seems to be the crux of many Covid-19 complications. The oxidative nature of UBI may have mechanisms in common with ozone therapy and other oxygen therapies. Namely, we are reducing the oxidative stress on the immune system. Oxidative stress is an imbalance between free radicals and antioxidants in your body. Free radicals are oxygen-containing molecules with an uneven number of electrons. The uneven number allows them to easily react with other molecules. Free radicals can cause large chain chemical reactions in your body because they react so easily with other molecules. These reactions are called oxidation. They can be beneficial or harmfulThink of oxidative stress as synonymous with inflammation and inflammation is the root of most medical problems.Dr. Hamblin’s article is but one article concerning the use of light therapy. I think there is little doubt there is strong science behind the use of ultraviolet blood irradiation and for that matter phototherapy to treat a number of medical conditions. Although this seems like cutting edge therapy it is actually old. Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However, with the development of antibiotics, UBI use declined and it has now been called “the cure that time forgot”. Hopefully more research on various types of blood irradiation will be performed. I would also like to include a few slides from my lectures. These slides concern the use of phototherapy. The first slide is a summary of phototherapy.As we can see there are a myriad of beneficial aspect to light therapy. I will draw your attention to sentence six, “Whatever cells are designed to do will be improved by light therapy”. The next slide shows some of the many benefits of phototherapy in pictorial form.The takeaways from the above slide is that light therapy is intimately involved in cell energy production, positively impacts cellular repair and healing, stimulates the immune system. As President Trump said “GET THE LIGHT INSIDE THE BODY” and hopefully control the covid-19 virus. Certainly, no guarantees or cures but it might be a step in the right direction. Actually, we can take things to the next level by giving the patient certain medications which are called photosensitizers. Photosensitizers make light therapy work even better. However, this is a discussion for a different day. I will end this quick blog with a rather somber thought. Covid -19 is certainly a serious problem for our planet and I believe we will conquer it. I would like to present some information by the Rand Europe Think Tank. Unfortunately, there are much greater biological time bombs that may be facing us. One ticking time bomb we are facing is that of antibiotic resistance. Here is the chart of what we are facing, namely approximately 10,000,000 deaths per year caused by antibiotic resistance. It might just be that blood irradiation may save the day. Meantime, stay safe and get some sunshine which is a primitive form of blood irradiation.Thanks,Dr. P DEATHS PER YEAR SECONDARY TO ANTIBIOTIC RESISTANCE 2050 2050Thanks,- Dr. P
Once in a while I like to write a blog that is not all science! I must say that I was initially a bit intimated by my schedule.I left Miami on Thursday evening, arriving in Sao Paulo 8 hours later on Friday morning.Interestingly, there were a number people that I knew at the meeting. I have taught in Brazil on numerous occasions. I will return in October to teach a course. I received a warm Brazilian welcome. I was very impressed by the quality of the meeting and the speakers. I felt honored to be one of the Keynote speakers.My talk was an interesting one. I discussed Stem Cell Aging Pathways. As I have said “how Stem cells age is how we age”. In my journey thru the world of Regenerative Medicine I have become convinced that these pathways may be the Holy Grail for Anti-Aging methods. These pathways are what I call the upstream causes of aging. If we correct these problems in the pathways we will affect downstream problems. One pathway I stressed was the Sirtuin Gene pathway. I discussed its dependence upon the supplement NAD and other methods of stimulating this pathway. I mentioned our experiences with Intravenous NAD and one of our secrete weapons which is the NAD kinase patch. I received a number of questions from the audience. One exciting aspect of the talk involved the introduction of some brand-new technology. Actually, I have used this technology for years. This technology involves transdermal patches which introduce signaling molecules to spine, tendons and joints. These are called P3 AI and P3 R patches. The name for this technology is SIGMOLECS. This will be a quantum leap for many regenerative physicians. They now have technology that we have utilized for years. These patches are now registered with the FDA. Below is a picture of the packaging of the patches.I suspect this will become an integral aspect of most regenerative procedures. Signaling molecules tell cells what to do and when to do it. This is essentially the basis of a PRP preparation and a branch of medicine called Cytokine Therapy.This technology seemed to be well received by the audience. Unfortunately, my time in Sao Paulo was very limited and later that afternoon I found myself in another 2-hour traffic jam on my way back to the airport facing my second night in a row on an airplane.After a 12-hour plane ride I arrived in Beverly Hills California where the Cell Surgical International Conference was being held.My lecture this time concerned the nuts and bolts of Regenerative Medicine as it pertains to stem cells. I stressed the basic science but put a twist on it to show how if one knows the basic science he then has the intellectual tools to make procedures better. This is the essence of a new field of medicine called Translational Medicine. Translational Medicine is a rapidly growing discipline in biomedical research and aims to expedite the discovery of new diagnostic tools and treatments by using a multi-disciplinary, highly collaborative, “bench-to-bedside” approach. The lecture was a whirlwind of slides. I showed how the immune system and the stem cells are so intimately related. Hopefully I opened up a few eyes on these topics. There were many different topics covered in the meeting all of which were engrossing. Some of the topics covered musculoskeletal conditions while other dealt with neurological conditions.One of my friends, Dr. Nathan Bryant, who is a world leading expert in Nitric Oxide medicine gave a great slide that reminds me of my journey in Regenerative Medicine. It is as follows“All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.” – Arthur Schopenhauer I always learn something from a meeting that I lecture at. At this meeting I met many old friends and some new ones.My staff from the Cayman Islands attended the meeting:All-in-all, it was a hectic weekend but it was rewarding on many different levels. I enjoy teaching and the comradery of the meetings.BTW people are asking me if I had Jet Lag. The answer is a resounding, “no.” By using my laser watch, jet lag is never an issue for me. The laser wrist watch helps my body produce various compounds which helps my body fight jet lag.Thanks, – Dr. P
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