Nobody likes surgery. It’s expensive. It’s disruptive. It can have tremendous risks and side effects. And none of this is to mention the long road to recovery often involved with even minor procedures. While we acknowledge that with certain injuries or medical issues surgery is unavoidable, there are many instances where regenerative medicine may be a better alternative. Here are the top five reasons why:
It goes without saying that the number one reason to avoid surgery is to avoid the complications that may arise from the surgery. Joint replacements. Shoulder, knee and hip pain. All of these surgeries carry risk. Cell-based orthopedic treatments can potentially help patients avoid invasive and intense surgeries.
Lower Risk of Complications
Since a patient’s own cells are used for regenerative cell procedures they are extremely low risk compared to traditional surgery. Another huge bonus is that there is no need for general anesthesia to be used during the procedure. In itself, this removes a large part of the risk when treating chronic pain.
Chronic Pain Relief
There are four ways that regenerative medicine can provide relief from chronic pain:
Healing damaged tissue
Building new tissue
Preventing scar tissue
We’ve talked about the lengthy recovery time associated with traditional surgery. With regenerative medicine procedures, patients are able to avoid the lengthy periods of downtime and painful rehabilitation that typically follow invasive surgeries.
When it comes to athletes and even weekend warriors, this is critical. It means less time on the sidelines of your favorite activity. Regenerative medicine patients are encouraged to move around as much as they comfortably can following the procedure and start physical therapy just a couple of days afterward.
Most people don’t know that with a regenerative medicine procedure, the healing continues for weeks and months after the procedure as the regenerative cells work to repair the damaged areas and improve the health of the tissues and bone.
For more information on PRP, MiniStem™ or MaxxStem™ regenerative medicine procedures, click here.
I recently read a fascinating article on Inside Hook’s website that I wanted to share some insights from. The article tackles issues that are very important for the fields of stem cell research and regenerative medicine. One of the more profound statements from the piece that has stuck with me is this one: “Some of the most effective anti-aging efforts take place outside of the lab, and boil down to thoughtful lifestyle adjustments.”
The focus of the article is on the Hormesis Effect. I became aware of the Hormesis Effect quite some time ago. Hormesis is defined as a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition, which can border upon toxicity. In layman’s terms, “hormesis occurs when the body experiences a concentrated period of intense pressure.”
One thing to keep in mind is that a small amount of stress is very beneficial, while a larger amount can be detrimental. This article discusses the effective hormetic responses the body has to a variety of self-induced strategies, from intermittent fasting and exercise to intermittent hypoxia training and even heat/cold therapy.
We have applied some of these same principles to our regenerative cell procedures, such as exposing the cells to cold temperatures (4 degrees centigrade and hypoxia).
This is an excellent beginner article for people who are not that familiar with the topic of hormesis, but want to learn more about it and at the same time learn how to improve their health!
- Dr. P
Read the full article here: https://www.insidehook.com/article/health-and-fitness/healthy-hormetic-stress
Be honest. You love products and foods that are high in antioxidants. If someone asks you why a face cream works or why you like a certain smoothie you quickly answer, “because it’s high in antioxidants!”
But do you really have any idea what they are? Or what they do? Or why they’re so powerful?
It’s O.K. if you’ve answered “no” to all three of those questions. Most people do. But we’ve got your back.
What Are Antioxidants?
Antioxidants prevent the oxidation of other molecules. And what is oxidation? Oxidation is a chemical reaction that produces things called free radicals. Free radicals cause cell damage and can lead to everything from cancer to a variety of premature aging conditions.
What, Exactly, Do Antioxidants Do?
Antioxidants may protect your cells from free radicals, which in turn may help stave off all kinds of diseases, including heart disease and cancer.
Why Are Antioxidants Powerful?
Antioxidants are powerful because they counteract free radicals. While free radicals do have some positive benefits (like helping our immune system) if too many are produced they can run amok and take our lives with them. An overloading of free radicals is very bad news for our bodies. Fortunately, antioxidants have the power to equalize free radicals and create a harmonious balance with free radicals in our bodies.
What, Exactly, Are Regenerative Cells?
Regeneration is a process where human tissue can heal itself following damage. Regenerative medicine is so unique because it can deliver regenerative cells to damaged areas of the body to potentially heal or improve them.
Regenerative Cells are unique cells in our body, which have the ability to become many different types of cells. These cells can be removed from the bone marrow and fat tissues and then delivered to injured or degenerated areas, such as hip or knee joints suffering from arthritis.
How Do Regenerative Cells Work?
As part of a cell-based treatment, regenerative cells can be collected from bone marrow, fat tissue, and blood with minimal discomfort.
These cells can then be processed in a state of the art laboratory utilizing the latest technology.
Finally, the regenerative cells, in combination with natural growth and healing factors, can be injected where they are needed – such as an inflamed hip or knee joint.
Over time, the cells can potentially repair and regenerate the damaged tissues, resulting in relief of pain and improvement in mobility and function.
Institute Family, Nurse Bella here! Id like to take a moment to fill you in on
a new and very exciting supplement, recently developed by Dr. Purita, that will
be instrumental in speeding up healing times and increasing overall quality of
game changing supplement goes by the name of Stem Cell Activator and it was
developed to do just that! The main active ingredient in the formula is:
● Velvet Deer Antler:
● Has been
known to stimulate Insulin-like Growth Factor 1 (IGF-1), which in turn stimulates
Human Growth Factor (HGH). In English, this means that velvet deer antler can
help to speed the healing process by rebuilding tissues. This includes bones,
connective tissues, and even lean muscle mass! As if this wasnt intriguing
enough, our formula also contains the purest and most potent form of velvet
deer antler on the market.
know, this sounds great already, but there are far more ingredients in the
formula that compliment the action of velvet deer antler very effectively:
● An amazing
stem cell stimulator. If youve ever had a VSEL treatment with us, you have
taken this supplement to boost your circulating regenerative cells before we
drew your blood! Fucoidan is derived from a type of brown seaweed that is
frequently found in Japan and is specifically consumed highly in Okinawa, where
people live the longest and healthiest lives in the world. Fucoidan supports
the immune system and has anti-tumor, anti-inflammatory, anti-oxidant, and
● Derived from
resveratrol: one of the best anti-aging supplements around! Pterostilbene can
help lower cholesterol, blood pressure, improve memory, and even prevent
● An amino
acid with antioxidant properties that also promotes the health of the eyes,
brain and heart.
● Black Raspberry Extract:
antioxidant that is instrumental in promoting chromosomal health.
● An herb
that is a great mood booster, promotes mental stamina, reduces the stress
hormone cortisol, and even combats depression.
intestinal inflammation and promotes a healthy gut lining.
● Blueberry Extract:
● Added to
the formula to promote heart health, decrease inflammation, and even add a
great blueberry taste!
formula is amazing for anyone looking to feel stronger, speed up their recovery
time after an injury, procedure, or even after daily exercise! Stem Cell
Activator is an excellent addition to any supplement regimen for anyone!
Disclaimer: due to the potency and
nature of the mechanism of action of the active ingredients, please discuss the
use of this product with your healthcare provider and use caution with any
history of cancer or hormonal balance.
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.Learn more about EBO2 here.
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
There now seems to be intense interest in EBO2 techniques. Copious volumes of research have provided evidence that Ozone’s dynamic resonance structures facilitate physiological interactions useful in treating a myriad of pathologies. The comment of Ozone opponents is that ozone therapy looks like a panacea for all diseases. Indeed, it seems so, but in reality, this is due to the multitude of compounds originated at first from the reaction of ozone with body fluids, and eventually able to display pleiotropic effects delivered by different organs.
Ozone can be considered a “PRODRUG”. What exactly is a Prodrug? A prodrug is a medication or compound that, after administration, is metabolized into a pharmacologically active drug. Instead of administering a drug directly. The following illustration shows how a prodrug works:
One of the issues raised by the scientific community is: how does Ozone really acts on Humans? Ozone is quite different from a drug and its action is not a consequence of a binding reaction between one molecule (drug) and one receptor (cellular membrane protein). For this reason, we cannot look at Ozone in the classical terms of pharmacology.
Ozone like other agents, and unlike the common drugs that act on a specific receptor, induces small stress to the whole cell when used at adequate doses. This, in turn, triggers a series of intracellular metabolic processes and promotes a myriad of intracellular activities. Because of these reactions, the defense mechanisms of the cell are alarmed and pushed to improve cell activity, explaining in part the surprising therapeutic actions of Ozone. By the same token Ozone is not truly a prodrug since it can have direct effects on phospholipids, lipoproteins, the cell membrane envelopes of bacteria and viruses. These bioactivities can eradicate bacteria and viruses.
In order to fully understand the biochemical basis underlying the pharmacological effects of ozone, it is important to illustrate its effects on various coenzymes. These coenzymes are responsible for ozone cell metabolism regulation. These effects on metabolism have profound effects on many aspects in the body. One of the significant effects of ozone is the acceleration of glycolysis. Glycolysis results in breaking glucose into pyruvate and getting a very valuable H+ hydrogen ion. The free energy released in this process is used to form the high-energy molecules ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide). ATP is cellular energy that all cells depend upon. Ozone will allow the ratio of NAD/NADH to be about 700/1. A fundamental condition for guaranteeing the continuity of this process is the reoxidation of NADH as it occurs following ozone exposure. The NADH is converted to NAD+.
The above diagram shows some important relationships. The ratio of NAD/NADH should be about 700/1. Ozone will stimulate the NQO1 gene which has profound effects on this ratio. NQO1 also stimulates the Sirtuin genes which are very significant in anti-aging and general well-being.
As far as protein metabolism, ozone intervenes mainly due to its remarkable affinity towards sulfhydryl groups. A sulfhydryl is a functional group consisting of a sulfur bonded to a hydrogen atom.
The sulfhydryl group is one of the most reactive and ubiquitous binding molecules in biological systems. It is found in most proteins and also in a few low molecular-weight substances such as glutathione, CoA (Coenzyme A, notable for its role in the synthesis and oxidation of fatty acids), lipoate, thioglycolate, and free cysteine. It is the most studied of chemical groups, particularly in relation to its role in enzymatic activity and properties of proteins.
Similarly, ozone reacts with essential amino acids such as methionine, tryptophan, and other amino acids containing sulfur (i.e., cysteine). In this case, the amino acids are protected from ozone inactivation by two reactions that prevent their degradation: first the oxidation of glutathione and then the oxidation of the coenzymes NADH and NADPH, which are key reactions in the biochemical mechanism of ozone. Nicotinamide adenine dinucleotide, or NAD, is in all living cells, where it functions as a coenzyme. It exists in either an oxidized form, NAD+, which can accept a hydrogen atom (i.e., a proton), or a reduced form, NADH, which can donate a hydrogen atom. Note that "donate a proton" and "accept a pair of electrons" translates to the same thing in biochemistry. Nicotinamide adenine dinucleotide phosphate, or NADP+, is a similar molecule with a similar function, differing from NAD+ in that it contains an additional phosphate group. The oxidized form is NADP+, while the reduced form is NADPH.
Finally, ozone reacts directly with unsaturated fatty acids, which have a double carbon bond and are therefore available for an oxidative reaction, leading to the formation of peroxides following cleavage of the lipid chains. In addition to the direct contributions to cellular metabolism described above, both NADH and NADPH may take part in other important physiological processes, including mitochondrial functions, calcium regulation, antioxidation and its counterpart (the generation of oxidative stress), gene expression, immune functions, the aging process and cell death. As a result, some biochemistry researchers have proposed that further investigation
Ozone dissolved in the plasma reacts immediately with a number of biomolecules producing two compounds. There are two compounds Reactive Oxygen Species (ROS) and Lipid Oxidative Products (LOPS). They represent the “ozone messengers” and are responsible for many of the biological and therapeutic effects attributed to ozone. ROS are produced immediately in the early phase (mainly Hydrogen peroxide or H2O2) and are responsible for the early biological effects on blood (erythrocytes, leucocytes, platelets). Hydrogen peroxide, now universally recognized as one of the main intracellular signaling molecules, acts on the different blood cells. Hydrogen peroxide is one of the most significant cytokine inducers in white blood cells. The mass of erythrocytes mops up the bulk of hydrogen peroxide. H2O2 diffuses easily from the plasma into the cells and its sudden appearance in the cytoplasm represents a triggering stimulus. This stimulus depends upon the cell types. Different biochemical pathways can be concurrently activated in erythrocytes, leukocytes and platelets resulting in numerous biological effects.
On the other hand, Lipid Oxidative Products (LOPS), which are simultaneously produced at the same time as ROS have a far longer half-life. They reach the vascular system and interact with several organs, where they trigger late effects. Some of these real targets are liver, vascular system, while other organs are probably involved in restoring normal homeostasis including the central nervous system, gastrointestinal tract, mucosal associated lymphoid tissue. The LOPS molecules can elicit the upregulation of antioxidant enzymes such as superoxide dismutase (SOD), GSH-peroxidases (GSH-Px), GSH-reductase (GSH-Rd) and catalase (CAT). Moreover, LOPS exert a neuroimmunomodulatory effect highlighted by a feeling of well-being reported by patients during ozone therapy.
OZONE THE WONDER DRUG
Ozone is a wonder drug because it can produce four extraordinary phenomena: 1) the induction of Oxidative Shock Proteins (OSP) 2) the upregulation of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) 3) the reduction and/or normalization of oxidative stress; and 4) the release of bone marrow stem cells.
Ozone mobilizes bone marrow stem cells (BMSC) and produces LOPS, which induce Nitric Oxide synthase (NOs). This produces inhibition of platelet-leukocyte aggregation.NO is responsible for producing neovascularization and neoangiogenisis. Also, NO activates MMP-9 (matrix metalloproteinase 9) which is indispensable for stem cell mobilization. MMP-9 actually releases the bond that holds stem cells in the bone marrow and releases them to the circulation. The production of Nitric Oxide is one of the main mechanisms by which hyperbaric oxygen will increase stem cell output from the bone marrow. These numbers will include a wide variety of the stem cells that are released from the marrow including Hematopoietic and Mesenchymal Stem cells. Ozone forms lipid oxidative products which in turn produce nitric oxide which makes proteases which release stem cells from the bone marrow into the circulation. The release of stem cells from the marrow is a multi-step process dependent on many different factors.
We can see from the following diagram the very process of how Ozone affects stem cell release:
The above diagram shows release of stem cells (HSC) from the bone marrow to the circulation. This is very dependent upon the production of MMP-9. This stimulation releases the stem cells from the bone marrow and allows them to go into circulation.
The fact that Ozone releases stem cells from the bone marrow is very important. It should be mentioned that this concept is similar to the mechanism of hyperbaric oxygen. In the above diagram it is demonstrates that LOPS, throughout the treatments, act as acute oxidative stressors in the bone marrow microenvironments activate the release of metalloproteinases, of which MP-9 particularly may favor the detachment of stem cells. These cells, once in the blood circulation, may be attracted and home at sites where a previous injury (a trauma or an ischemic-degenerative event) has taken place. The potential relevance of such an event would have a huge practical importance and will avoid the unnatural, costly and scarcely effective practice of the bone marrow collection with the need of the successive and uncertain re-infusion.
OZONE AND OXIDATIVE STRESS
One of the most important aspects of Ozone therapy is activation the Nuclear Factor Erythroid 2 Related Factor 2 commonly known as NrF2. NrF2 is like the body’s “missile defense system”. It helps keep oxidative stress under control. Oxidative stress arises from free radicals. Free radicals are compounds which have free electrons. These rogue molecules can cause havoc by “stealing” electrons from other molecules. Some free radicals are capable of damaging the DNA or crippling the proteins and lipids that make up various tissues. As a result, these crucial molecules become damaged, weak, dysfunctional, or otherwise incapable of fulfilling their roles. Produced deep within cells as a byproduct of ordinary energy-producing processes, free radicals are thought to be responsible for aging and disease, including even cancer. How does NrF2 protect us from free radicals?
NrF2 is basically like a thermostat. But instead of regulating temperature, it regulates stress levels known as oxidative stress. It responds by binding with the DNA, signaling the cells to make thousands of molecules to shield the cells. They will later activate a new response to form a new barrier. This “barrier” will protect the cells from future stress. Furthermore, Nrf2 will remove the toxins that cause cell damage and boost the normal function. Both of these functions will return the stress levels to normal, minimizing the negative effects.
We must realize that we do not want to constantly have NrF2 activated. Ozone is a selective NrF2 activator. How does this work? Ozone produces Antioxidant Responsive Elements (ARE). Antioxidant responsive elements (AREs) mediate the transcriptional induction of a battery of genes which comprise much of this chemoprotective response system and ultimately the NrF2 pathway.
Under normal conditions, Nrf2 is expressed at very low levels, and is mainly sequestered in the cytoplasm by its specific inhibitor called Kelch-like ECH associated protein-1 (Keap-1) that also promotes its rapid degradation. The effectiveness of this mechanism allows a rapid turnover of Nrf2, which displays a half-life of a few minutes. Under specific stimuli, Nrf2 dissociates from Keap1 and translocates into the nucleus and transactivates the ARE-driven genes. These genes encode for proteins involved in a multitude of vital biological functions which include protein homeostasis, oxidative stress response, detoxication, DNA repair, proliferation, autophagy (body's way of cleaning out damaged cells), mitochondrial biogenesis and function, inflammation, and the metabolism of lipids, carbohydrates and amino acids. When you stimulate NrF2 you have a healthier patient.
The following illustration shows these concepts:
NrF2 goes on to control a wide variety of processes in the body including proper formation of proteins, control of inflammation, healthy mitochondrial function, and healthy adipose tissue.
WHAT ARE SOME OF THE OTHER EFFECTS OF OZONE THERAPY
The oxidation chemistry of ozone is known to produce Hydrogen Peroxide (H2O2) that enters cells where it has various effects. In red blood cells (RBCs), it shifts the hemoglobin dissociation curve to the right and facilitates release of oxygen, while in leukocytes (WBCs) and endothelial cells it can stimulate the production of interleukins, interferons, growth factors and nitric oxide production. In platelets it favors release of growth factors. As a further aspect of the therapeutic action of ozone, there is the capacity to regulate the cell antioxidant network positively. This aspect is of key relevance in all those conditions in which an imbalance between production and neutralization of ROS (Reactive Oxygen Species) may develop, resulting in oxidative stress. Again, this relates to the implications of the NrF2 pathway and its activation or inactivation. These events may turn into a self-feeding cycle in which oxidative stress is sustained by micro- and macro-inflammatory reactions that lead to cell and tissue degeneration and necrosis. This scenario features the pathogenetic role of oxidative stress in several chronic, degenerative disease states such as chronic viral infections, atherosclerosis, tumor growth, neurodegenerative diseases and accelerated aging. Ozone can help stop these problems in their tracks.
HEAT SHOCK PROTEINS
Another aspect of Ozone therapy is the production of HEAT SHOCK PROTEINS (HSPS). Shock proteins are a family of proteins that are produced by cells in response to exposure to stressful conditions. They were first described in relation to actual heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light (this is one of the reasons we are utilizing a UVA light to stress the blood cells) and during wound healing or tissue remodeling. We can also stimulate Heat Shock Proteins by using a sauna or by subjecting our body to very cold temperatures.
Many members of the Heat Shock Protein group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is genetically regulated. In the packed, busy confines of a living cell, hundreds of chaperone proteins vigilantly monitor and control protein folding. From the moment proteins are generated in and then exit the ribosome until their demise by degradation, chaperones act like helicopter parents, jumping in at the first signs of bad behavior to nip misfolding in the bud or to sequester problematically folded proteins before their aggregation causes disease. People often mistakenly think that proteins are free to live out their lives in a cell. As it becomes increasingly clear that folding is not a once-in-a-lifetime event for proteins but instead a part of day-to-day life in the cell. Scientists are discovering that problems in this sophisticated system of protein folding are implicated in diseases as diverse as cancer, diabetes, and Alzheimer’s. As time goes on we are finding more and more diseases associated with misfolded proteins. This will open up a new realm in medicine in which Ozone therapy and Photo modulation may be integral players on taking the science of Heat Shock Proteins to the next level. Not only is Heat Shock Proteins important in disease control but it seems to have a place in improving athletic performance.
The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). The following illustrations demonstrate the very important work of the Heat Shock proteins:
HSPs are found in virtually all living organisms, from bacteria to humans. HSPs are known to modulate the effects of inflammation cascades leading to the generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of human inflammatory diseases and cancer. There is a scientific push for studying the HSPs for the treatment of various inflammatory diseases and cancer. Also, it appears that a safe and effective method of stimulating HSPs is by the use of Ozone in blood. Heat shock proteins may play a critical role in reducing recovery time and boosting muscle development.
The following illustration shows the mechanism of HSPs:
We can see that the HSPs can have profound implications for a person’s well-being. This is a field where more research will certainly be needed. We can see that when we have an altered expression of Heat Shock proteins many bad things happen. It appears that many autoimmune diseases are related to altered Heat Shock proteins. The following diagram is a good illustration of this.
Chronic inflammatory conditions are accompanied by a partial or sometimes large resetting of the immune system to a pro-inflammatory and pro-oxidant state. This response has gross implications also in the integrity of vascular components and may represent a sensitive therapeutic target of chronic, degenerative conditions. On the basis of these theoretical foundations, reported therapeutic applications for ozone therapy were the activation of the immune system in infectious diseases and cancer, and an improved oxygen utilization and release of growth factors that can reduce the extent of ischemic lesions in vascular diseases.
- Dr. P