Our red light therapy treatments are delivered via a device called the LightStim® LED bed. The bed houses 18,240 therapeutic, glowing LED lights, which utilize red (630 and 660 nm) and infrared light wavelengths (885 and 940 nm).This is the first bed of its kind to be FDA-cleared for therapeutic use. The LightStim® LED bed can be combined with many of our other innovative therapies for aesthetics, anti-aging, healing and overall wellness.The amount of time one spends on the bed is variable. A typical treatment is about twenty minutes to an hour. The main light source in the LightStim® bed is visible red light. This is a cool light and does not generate much heat.
The 4 Main Health Benefits of Red Light Therapy:
Red light interacts with photoreceptors in the body like cytochrome c oxidase within the mitochondria to stimulate energy production and give an electrical charge to water.
Red light absorption converts light energy into signals that can stimulate biological processes. Water is the number one red/infrared light chromophore in the human body absorbing a great deal of the light and using it to function as a biologic battery. The “battery” is charged by hydrogen ions.
Hormesis (hormetic stress):
Hormetic stress is the ideal level of exposure to stressors. Underexposure to stress could leave your body unchallenged, while overexposure could lead to health problems. Hormetic stress is that “sweet spot” where stress could be beneficial. Red/IR light creates beneficial reactive oxygen species (ROS) on a transient basis. The hormesis effect stimulates the mitochondria to make adaptations to allow the cell to become stronger and more resistant to a broader range of stresses by activating the cells internal response system to boost antioxidant production.
This not only boosts antioxidant production but allows the cell to have an increased ability to reduce toxic compounds. Ultimately, this activates mitochondrial biogenesis creating a greater number of mitochondria.
Red and infrared light therapy stimulates the mitochondria to communicate with the cell nucleus to upregulate gene expression. The genes then produce compound, which are involved in mitochondrial biogenesis, antioxidant defenses and detoxification.
We are aware that certain compounds have unique properties in that they can be activated by light therapy. Photosensitizers are substances that make your cells or tissues more sensitive to light.
While low-dose methylene blue and low-level near-infrared light may produce different cellular effects, both interventions cause a similar up-regulation of mitochondrial respiration with similar benefits to protect nerve cells against degeneration.
The bottom line is that the methylene blue used in conjunction with the red-light therapy can help increase ATP production. Curcumin is another photosensitizer compound.
In my research over the last year, I have come across more and more articles discussing the value and importance of prolonged and intermittent fasting as it relates to regenerative medicine.
While studies on intermittent fasting, or IF, as it’s known in shorthand, are published in scientific journals, the results and the benefits are steadily making their way into the mainstream.
I recently read an article in Longevity.Technology that compared prolonged fasting with IF that piqued my interest and I wanted to share some of the finer points with you.
ONE: How does fasting work?
In the simplest form, fasting works by activating a process called ketosis. Ketosis occurs when you haven’t eaten for an extended period of time and your body doesn't have enough carbohydrates to burn for energy. Instead, it burns fat and produces ketones, which it can use for fuel. This is called being in “ketosis”.
TWO: What is the difference between IF and prolonged fasting?
Prolonged fasting occurs when you choose to not eat for a long period of time; anywhere from 24 to 48 to 72 hours. You consume water and occasionally some nutrients during this time, but little to no calories. As you can imagine, this strategy of fasting is too difficult for many people to attempt or maintain.
Thankfully, practicing IF allows you to obtain many of the benefits of prolonged fasting with a much more manageable eating schedule. The sweet spots for these IF regiments is typically between 18 and 24 hours, which is why the 16-hour fast followed by an 8-hour eating window is so popular. Many who follow this schedule begin their fast at 8pm and don’t eat until the following day at 12pm.
During that eating window starting at 12pm, people practicing IF eat all of their meals for the day. You may feel like you can loosen up on your diet since you just fasted, but I would not recommend that. I’d still limit or ban sugars altogether and cut carbohydrates down to a bare minimum.
THREE: Does fasting affect longevity?
Whether you choose to try IF or prolonged fasting, both methods affect nutrient sensing pathways. One such pathway is called the AMPK pathway which helps drive glucose into the cells and thus decreases glucose levels. Stimulation of the AMPK pathway definitely is associated with longevity. At the same time, fasting also down-regulates the mTOR pathway.
FOUR: What are the other benefits of IF?
One very important aspect of intermittent fasting involves the process of autophagy. Just as important as the weight loss aspects of IF, autophagy has tremendous health benefits as well.
Autophagy plays a housekeeping role in removing improperly folded or aggregated proteins, clearing damaged organelles (intracellular structures), such as mitochondria and endoplasmic reticulum, both of which are important in energy production.
In addition to the elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, which protects against genome instability and prevents necrosis.
Taking things one step further, autophagy plays a key role in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases and infections.
In conclusion, IF may provide a host of health benefits and for many people it is certainly worth practicing.
- Dr. P
This is the recent article that I found valuable:
For good reason, Intermittent Fasting (IF) is one of the most talked
about health trends of the moment. Previously, calorie restriction was thought
to be one of the best ways to reverse the clock of aging, but intermittent
fasting could be even better!
Intermittent fasting is typically restricting your eating hours to 8
hours per day and your fasting hours to 16 hours per day. During the fast, it
is preferable to drink lots of water and even drink a bit of black coffee if
you enjoy your morning jolt!
There are many different structures to an intermittent fasting
regimen, and it can be tailored to any lifestyle.
There are a ton of benefits that come with a 16 hour fast, but our top
● Weight and fat loss!
● Helps decrease cholesterol.
● Helps prevent type 2 diabetes.
● Helps to improve blood pressure!
A recent Harvard
study showed that IF helped in preventing disease and promoting overall health!
There's a lot of noise in the supplement world about what to take to
feel or look younger. We've combed through the research to share the five
supplements that have the most promising research behind them for their
Need to Know About EGCG
Lets spill the tea on EGCG. Epigallocatechin gallate (or EGCG) is a type of catechin that is found
in many teas and is known for its antioxidant and anti-inflammatory effects, as
well as a wide range of health benefits!
EGCG is found in varying concentrations in many
teas, but is found mostly in green tea. Other teas like oolong and black teas
are partially or fully oxidized, so they have much lower concentrations of
EGCG. If you're somewhat of a tea connoisseur, you'll know that tea can vary
from region to region, whether it is grown in shade versus sun, and even differ
depending on what season the tea is harvested in. Research has shown that
Japanese steamed teas have higher catechin concentrations. Tea from the second
harvest is usually higher in EGCG versus the first harvest as well. On the tea
plant itself, the younger plant leaves toward the top have more EGCG over the
mature leaves on the lower part of the plant.
EGCG is great for heart health by decreasing
inflammation and reducing blood pressure. Studies have also shown that EGCG can
protect brain cells from oxidative stress and increase brain function. This
helps to improve task performance and display improved memory recall.
Additionally, the green tea rich in EGCG and caffeine have been linked to
assistance of weight loss through balancing hormones that regulate
thermogenesis, which is how your body burns calories to produce energy/heat.
Individuals with skin issues like dermatitis and rosacea have been known to
show improvement with EGCG as well. Topical green tea extract can help with
skin elasticity, inflammation and other signs of aging.
Taking EGCG can also help to reduce liver
enzyme levels through reduction of inflammation and oxidative stress. However,
excessive intake of EGCG has been linked to increased risk of liver damage, so
you should always consult with your doctor if you plan on taking any
supplements with EGCG, or consume EGCG in higher than normal quantities. Your
doctor should test your liver function regularly in order to determine if EGCG
is an appropriate option for you.
Grab a cup, let it steep, and RELAX!
The Top 8
Benefits of Curcumin
Curcumin is derived from the rhizomes of the curcuma longa linn plant,
a member of the ginger family (zingiberaceae). Curcumin, the active ingredient
in turmeric, aids in management of oxidative stress, inflammatory conditions,
metabolism, arthritis, anxiety, and even hyperlipidemia. Curcumin can be
instrumental in helping to decrease exercise induced inflammation and muscle
soreness, enhancing recovery and performance.
acts as a transcription agent to turn on genes that have been mistakenly
silenced and can even activate p53, the tumor suppressor gene, which can keep
cancer cells at bay.
The Top 8 Benefits
potent anti-inflammatory properties.
decrease your risk of cancer.
reduce your risk of heart disease
relieve arthritis pain.
It can help
decrease your cholesterol
assist in preventing alzheimer's
It can help
in the prevention and management of diabetes
It can help
increase your immunity
It is a
It works on many pathways in the body to
with supplementing curcumin is that it is not very bioavailable alone. Here at
IRM we carry the most bioavailable oral preparation of Curcumin, called
UltraCur, and we even have Curcumin available in IV form! The IV form is an
absolute game changer, as this amazing anti-inflammatory powerhouse can now be
delivered straight into your bloodstream!
The Benefits of Taking NAD+
NAD+ is an essential coenzyme that we cant live without. It is
present in the mitochondria of each cell and declines 50% by age 40-60. The
mitochondria are known as the powerhouse of the cell and make ATP or energy
within the cell. Without sufficient NAD+ our mitochondria struggle to make
sufficient energy, which can be very taxing to our vital organs. Replenishing
NAD+ stores can lead to improved athletic performance, slow the process of
aging, and revitalize our hard working organs. NAD+ plays a key role in
metabolism and DNA repair, which is very important in the prevention of chronic
illnesses and even cancer. The organs with the highest concentrations of NAD+
are the heart and brain, so the lack of NAD+ can put these organs at risk for
degenerative conditions (ie. Alzheimers). For this reason, NAD+ can potentially
be very effective in preventing dementia, Parkinsons, and even multiple
sclerosis. NAD+ is given via intravenous infusion and takes about two to four
hours and depends on each patients tolerance of the drip. During the drip, some symptoms that most
people experience are chest tightness and/or butterflies in their stomach, but
everyone is different. These symptoms are completely benign, and will go away
within 20 seconds of stopping the drip. We like to think of the sensation of
these symptoms as our cells getting the boost of energy that they'd been
working so hard for! Typically, our areas of issue or disease are the areas of
the body in which NAD+ is lacking, thus we typically feel the symptoms in those
areas. In short, you'll feel it where you need it!
At The Institute, we offer the most comprehensive NAD+ protocol to
give you the boost that you need without any baggage. This baggage that I speak
of may come in the form of homocysteine production and senescence, both of
which we are able to prevent here at the institute. Prior to the infusion, we
supply each patient with a supplement called Trimethylglycine (TMG), which
provides the body with methyl and assists in the tolerance of the infusion.
Further, the methyl provided by the TMG prevents the production of
homocysteine, an amino acid that can cause damage to the arteries, during the
NAD+ infusion. This homocysteine, if produced even after TMG supplementation,
can be broken down by Vitamin B6. For this reason, we end each NAD+ IV with an
IV push of Vitamin B6. As far as senescence is concerned, NAD+ has the tendency
to help our cells thrive and get stronger, even the scenecent ones. Senescent
cells are those cells that should've died, but are continuing to live on and
secreting things like inflammatory proteins. To prevent these cells from living
on, we supplement quercetin with our NAD+ treatments as a senolytic. This
allows the NAD+ to boost up the healthy cells and the senescent cells to die
off as they should. Lastly, we finish the infusion with a supplement called
SAMe. This helps to potentiate the effects of the NAD+ infusion and helps you
to feel more energized for even longer. We are currently one of the only
clinics comprehensively taking care of all of the baggage that comes with an
NAD+ infusion, and leaving you to only receive the amazing benefits!
The Most Exciting
Anti-Aging Antioxidant: Resveratrol
Resveratrol is a plant compound that is an excellent antioxidant. Plants actually
produce resveratrol in times of distress caused by a bacteria, virus or fungi
because it can help fight off these pathogens. Along with being an antioxidant,
resveratrol also has anticancer and neuroprotective properties. For years,
resveratrol has been used to treat infectious and inflammatory conditions, but
its most notable benefit is its cardioprotective properties. Resveratrol can
lower blood pressure, by increasing the production of nitric oxide in the body.
This is important because nitric oxide actually relaxes the blood vessels,
decreasing blood pressure, and decreasing the workload on the heart.
Furthermore, resveratrol can help lower body weight, total and LDL or bad
cholesterol, and increase HDL or good cholesterol. Resveratrol can also
increase insulin sensitivity, by activating the AMPK pathway (the same pathway
activated by the diabetes drug Metformin), therefore decreasing the risk of
developing type 2 diabetes. Lastly, resveratrol can ease joint pain by
preventing the breakdown of cartilage in the joints and possibly stopping
osteoarthritis in its tracks. For these reasons, in many animal studies,
resveratrol has been shown to lengthen lifespan.
Resveratrol is found in many plant foods, especially the skin of
grapes, blueberries, raspberries, mulberries, and peanuts. So, consider reading
this a sign to have a glass of wine tonight, you know, for the health benefits.
One of the biggest issues with supplementation of resveratrol is its
poor bioavailability. For this reason, we have an IV preparation of resveratrol
at IRM that will be delivered directly into the bloodstream for maximum
Similarly to resveratrol, pterostilbene is an antioxidant and
antimicrobial compound found in plants. Pterostilbene also has anticancer,
anti-inflammatory, anti-diabetic, and vascular protective properties.
Resveratrol may be superior for its cardioprotective effects, but
pterostilbenes anti-inflammatory and anticancer effects are far superior.
Pterostilbene has strong neuroprotective effects and has been shown to increase
cognitive abilities as well as slow down the process of aging by promoting DNA
repair! Furthermore, pterostilbene stimulates the AMPK pathway, increasing
insulin sensitivity and preventing the onset of type 2 diabetes.
Pterostilbene can be found in blueberries and grapes, but unlike
resveratrol, does not make it through the process of wine making, so you'll
have to eat the grapes to reap the benefits of this compound. Pterostilbene is
also more bioavailable than resveratrol, making it more easily absorbed orally.
Feel Young Again
What is CoQ10? CoQ10 or (coenzyme Q10) is
a fat-soluble nutrient that helps us produce energy, and is found naturally in
the body. Unfortunately, as we age, our bodies produce less and less CoQ10.
Lower levels of CoQ10 can lead to muscle weakness and fatigue, higher blood
pressures, and slowed thinking.
CoQ10 has been found to help with symptoms of
heart failure by restoring optimal levels of energy production. This increased
energy production has been linked with alleviating and even preventing
migraines, and is great for overall brain function. Along with improved
mitochondrial function, CoQ10s antioxidant properties can help protect skin
cells to make it look younger when applied directly.
Individuals may be deficient in CoQ10 if they
suffer from health conditions like heart disease, brain disorders, diabetes or
cancer, due to the increased demands by the respective tissues. Certain
medications like antidepressants, psychotherapeutics, and meds used to treat
heart disease are known to decrease levels of CoQ10.
You can find CoQ10 in a lot of foods that we
eat in our diets. However, most dietary sources have far less amounts of CoQ10
than when given as a supplement. Some of these foods include meats of all
forms, especially organ meats (liver, heart, etc.) and fatty fish. Soybeans,
nuts and seeds, and a variety of vegetables (especially broccoli) also contain
this vital nutrient.
CoQ10 has been known to lower blood sugar and
blood pressure, so individuals who are sensitive to this should take precaution
with CoQ10 supplementation. As always, consult your doctor if you're
considering taking CoQ10.
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.
We have known for some time that Ozone has some
anti-aging properties. But there are also some other anti-aging aspects of
Medical Ozone therapy that are not readily known. The above diagram
shows some interesting effects of medical ozone. In this particular case the
Ozone was administered intravenously. When Ozone is administered intravenously it
will form two different types of compounds. The first compound is hydrogen
peroxide (H2O2) which helps launch a cascade of reactions
which ultimately reduce inflammation in the body. Less inflammation is less
aging. More to come about this. In the above diagram we see that the Ozone is
reacting with the Poly Unsaturated Fatty Acids (PUFAs) found in the cell
membrane. Poly unsaturated fatty acids all have at least one double bond
linkage between carbon atoms. These double bonds cause them to bend, kind of
like how your arm bends at your elbow. This double bond limits the number of
hydrogen atoms that can bind to the carbon atoms, so the molecule is not as
saturated with hydrogen atoms as it could be. Thus, its considered
unsaturated. Unsaturated fatty acids that have one double bond are called
monounsaturated fatty acids (MUFAs). Unsaturated fatty acids with more than one
double bond are called polyunsaturated fatty acids (PUFAs). Get it? mono for one and poly for many.Polyunsaturated fats can be divided into 2 groups: omega-3s
and omega-6 fats. Two polyunsaturated fatty acids are regarded as essential
because the body cant make them they must come from food. The two essential
fatty acids are alpha linolenic acid (an omega 3 fat) and linoleic acid (an
omega 6 fat). Omega 3 fats, especially those found in seafood, are vital to
help control inflammatory reactions in the body.
POLYUNSATURATED FATS ARE USED AS BUILDING BLOCKS IN THE
MEMBRANES THAT SURROUND ALL THE CELLS OF YOUR BODY AND CONTRIBUTE TO THE
STRUCTURE OF THE BRAIN. The cell membrane seems to be the major area of
reaction between the Ozone and PUFAs.
In the first diagram we see that the Ozone reacts with the
Poly Unsaturated Fatty Acids located in the cell membrane. It forms a compound
called a Lipid Oxidation Products also known as LOPs. These LOPs react with a variety
of cells within the body. In the diagram I have circled in red two important
pathways in the body. These two are the AMPK and mTOR pathways. The effects of
these pathways have profound implications on our longevity. Other important
pathways include: 1. Sirtuin Pathway 2. Nuclear factor-kappa B (NF-kB) pathway 3. NRF2 pathway 4. FOXO pathway. These are very important pathways
especially when it comes to anti-aging and longevity.
Let us take a better look at the AMPK and the mTOR pathways.
The following illustration shows what happens when there is an AMPK deficit:
We are able to see that AMPK deficits lead to many conditions
associated with increased aging. While the opposite is true. Stimulate the AMPK
pathway and you will increase longevity.
The next illustration shows the rewards of increased AMPK:
The metabolic protein AMPK
has been described as a kind of magic bullet for health. Studies in animal
models have shown that compounds that activate the AMPK protein have
health-promoting effects to reverse diabetes, improve cardiovascular health,
treat mitochondrial disease and even extend life span. AMP-activated protein kinase, or AMPK, is known as a
master regulator of metabolism. AMPK deals how our body uses and transforms
is the switch that is the link between metabolic disease, inflammation, and
longevity. This switch tells our cells when to store and generate
energy-containing molecules such as fat, and when to hunker down and use
existing energy store. REMEMBER AMPK ACTIVATION WILL LOWER BLOOD GLUCOSE
LEVELS. THIS IS WHY WHEN SOME PATIENTS RECEIVE AN EBO2 OZONE TREATMENT OR OTHER
IV OZONE TREATMENTS, THEY SOMETIMES BECOME LIGHT HEADED. THEY ACTUALLY HAVE
DROPPED THEIR BLOOD GLUCOSE WHICH CAN EASILY BE REMEDIED BY GIVING THE PATIENT
A SOURCE OF GLUCOSE. THE AMPK PATHWAY HAS DRIVEN THE GLUCOSE INTO THE CELLS.
Thus, in order to further enhance the effects
of the Ozone it is suggested that that the patients follow through with
supplements which further stimulate the AMPK pathway. These supplements
include Resveratrol, Alpha
Lipoic Acid, Gynostemma (a form of Ginseng), Curcumin, Quercetin, and last but
not least is Berberine. These continue to stimulate the
AMPK pathway. The bottom line is the stimulating the AMPK pathway will allow
our bodies to utilize insulin much more efficiently which is a major hallmark
of anti-aging and longevity.
Another important anti-aging pathway is the
mTOR pathway. Actually, the blocking of this pathway is the mechanism
which results in anti-aging. mTOR means Mechanistic Target of Rapamycin.
To slow down aging we want to block most actions of the mTOR pathway. A medication
called Rapamycin will block the action of the mTOR pathway. Interestingly,
Rapamycin can function as an immuno-suppressant. It is used to prevent organ
transplant rejections among other things. When the mTOR pathway is over-activated by nutrients and
insulin, it will act to inhibit insulin signaling, thereby causing insulin
resistance. Insulin resistance is a hallmark of type II diabetes. Higher
insulin levels are associated with increased aging and increased blood glucose.
Acute treatment with Rapamycin abrogates insulin resistance in cells and
animals including humans. One study showed that chronic treatment with Rapamycin
prevented insulin resistance.
There are currently a number of studies that are utilizing
Rapamycin which blocks the mTOR pathway. The mTOR pathway is a master regulator
of cell growth. Think of increased mTOR activity
being an analog of the phrase LIVE FAST, DIE YOUNG, because too much
activity is good for
growth but bad for
lifespan. However, too little mTOR activity
is not beneficial either because it can disrupt healing and insulin sensitivity.
Ozone has an effect on the mTOR pathway mainly by its influence on the AMPK
pathway. AMPK hold the mTOR pathway in check. The following illustration shows
what the mTOR pathway actually influences. Namely, the growth of the cells. mTOR is involved in every aspect of cellular life and existence. In the case of inhibition of mTOR, we are actually trying to apply the brakes to cell growth and proliferation.
In addition, the mTOR pathway is a
direct target of the IGF-1 signaling pathway, which is a major driver of aging. Rapamycin is now available as a treatment modality for
anti-aging. Some supplements which simulate the effects of Rapamycin include
Curcumin, Green Tea Extract, Resveratrol and Pterostilbene, and Fistin. The
next illustration is an example of the mTOR pathway in action. What we see is
that the mTOR pathway is great for cell growth but ultimately it leads to shorter life span, remember, LIVE FAST AND DIE YOUNG. We can see that blocking the mTOR pathway has very beneficial results. It brings on longevity.
Both the AMPK pathway and the inhibition of the
mTOR pathway leads to the process of autophagy. Autophagy
seems to be a crucial component of many longevity protocols. What is autophagy?
humans abandoned their hunter ancestors roaming lifestyle and settled down in
permanent dwellings, they realized the importance and significance of
housekeeping. Ironically, our cells long preceded us to this realization as
they developed their own miniature housekeeping mechanism, known as autophagy
(Greek for self-eating). Autophagy does not only serve as a detoxification tool
but also supports cellular fitness by directing the resulting products from
waste hydrolysis towards energy production and cellular recycling. Mounting evidence indicates that autophagy plays a key
role in aging and aging-related diseases. Enhanced autophagy can delay aging
and prolong life span. The absence of autophagy leads to the accumulation of
mutant and misfolded proteins in the cell, which is the basis for the emergence
and development of neurodegenerative diseases and other aging-related diseases. The following illustration explains
The autophagic activity has
been found to decrease with age, likely
contributing to the accumulation of damaged macromolecules and organelles
during aging. Autophagy is becoming more and more important in the field
of anti-aging medicine.
Another aspect of Ozone Anti-Aging is
the effect that Ozone has on the NQO1 pathway. NQO1 pathway is very important
in the ratio of NAD+/NADH. Ideally, we like this ratio to be about
700/1. NQO1 keeps down the levels of NADH which is thought to be a marker of
aging. Also important about the NQO1 pathway is the influences it holds on P-53
P-53 is called the Tumor Suppressor
Gene. It is very important in dealing with cells that have significant DNA
damage. It will analyze a cell and either fix it or kill it. This is
extremely important for anti-aging. If the damaged cells are allowed to accumulate
they lead to Senescent cells. A Senescent cell is much like a Zombie cell. It
is the living dead. It can cause havoc on our immune system which leads to
aging. The next illustration is a good
example just how the P-53 gene works. It will analyze the cells and determine
their fate. They either survive or perish.
There are also some more well-known
aspects of aging that are associated with Ozone. One aspect includes the anti-aging
aspect that Ozone has upon the Sirtuin pathways via the influence of NAD+
production. Ozone helps produce NAD+ which has significant
implications on the function of the Sirtuin proteins. The Sirtuins are very
important for mitochondrial health. The Sirtuins seem to have an influence on a
number of other aging pathways. For instance, we see here the influences that
Sirtuin One protein has on a number of processes concerned with aging.
Lastly, and just as important, the
effects that Ozone on the NRF2 pathway are very influential in increasing our
longevity. We must remember that NRF2
pathway is a thermostat of anti-inflammation. This dovetails very nicely with a
process the name of which was just coined a few years ago, namely
Inflammaging essentially means that
inflammation leads to aging. This last illustration seems to sum up everything.
Ozone has effects on all these aspects of aging.Thanks, Dr. P
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
The more involved I become with stem cells and
the field of Regenerative Medicine, the more convinced I become of the
importance of the mitochondria. Many of us in clinical medicine seem to brush
over mitochondria. We now realize that many diseases are related in some way to
deficiencies of the mitochondria. Success in stem cell procedures may depend on
the health of the mitochondria. The above illustration shows the structure of
the mitochondria. Mitochondria
are rod-shaped organelles that can be considered the power generators of the
cell, converting oxygen and nutrients into adenosine triphosphate (ATP).
ATP is the chemical energy "currency" of the cell that powers the
cell's metabolic activities. Mitochondria
are often referred to as the powerhouses of the cell. They help turn the energy
we take from food into energy that the cell can use. But, there is more to
mitochondria than energy production. In
fact, only about 3 percent of the genes needed to make a mitochondrion go
into its energy production equipment. The vast majority are involved in other
jobs that are specific to the cell type where they are found. Here is another illustration of the inner
workings of the mitochondria
The mitochondria have two
membranes, an outer one and an inner one. Each membrane has different
functions. The Outer membrane allows small molecules to pass freely through the
outer membrane. This outer portion includes proteins called porins, which form
channels that allow proteins to cross. Most cellular stress
responses converge on the mitochondria. Consequently, the mitochondria must
rapidly respond to maintain cellular homeostasis and physiological demands by
fine-tuning a plethora of mitochondria-associated processes. The outer
mitochondrial membrane proteins are central to mediating mitochondrial
dynamics, coupled with continuous fission and fusion. These proteins also have
vital roles in controlling mitochondrial quality. When
cellular components like mitochondria become damaged or defective, they can be
recycled by cells through a process called autophagy, which literally means
self-eating. When mitochondria are degraded by autophagy, the process is
specifically referred to as mitophagy. Mitophagy often
occurs in defective mitochondria following damage or stress. This is
actually one of the important aspects of aging. As we age, mitophagy will
diminish resulting in increased damaged mitochondria. This has a snowball effect
in that it leads to increased reactive oxygen species (ROS), decreased
bioenergetics, and many age-related diseases. Mitochondrial damage may be the
seminal event in many different diseases. If we increase mitophagy we will slow
down aging. The following illustration shows the consequences of accumulated
The next structure to discuss is the inner mitochondrial membrane. It is
extensively folded and compartmentalized. The numerous invaginations of the
membrane are called cristae. Which are separated by crista
junctions from the inner boundary membrane juxtaposed to the outer membrane.
Cristae significantly increases the total membrane surface area compared to a
smooth inner membrane and thereby the available working space. The inner membrane is also loaded with proteins involved in electron transport and
ATP synthesis. This membrane surrounds the mitochondrial matrix, where the citric
acid cycle produces the electrons that travel from one protein complex to the
next in the inner membrane. The crista membranes contain most, if not all, of
the fully assembled complexes of the electron transport chain and the ATP
synthase. The following illustration demonstrates this concept. We see the two
membranes and subsequent ATP production. In review, at the inner mitochondrial
membrane a high energy electron is passed along the electron
released pumps hydrogen out of the matrix
space. The gradient created by this drives hydrogen back through the membrane,
through ATP synthase. As this happens, the enzymatic activity of ATP synthase
synthesizes ATP from ADP. This whole process is called oxidative
phosphorylation (OXPHOS), which is the main method and most efficient method
the body uses to make ATP. The more efficient this process the better in shape
Another structure present is the
mitochondrial ribosomes. Mitochondrial
ribosomes (mitoribosomes) perform protein synthesis inside mitochondria.
Throughout evolution, mitoribosomes have become functionally specialized for
synthesizing mitochondrial membrane proteins. Mitochondrial ribosomes resemble bacterial ribosomes and both bacteria
and mitochondria ribosomes share a slightly different genetic code from that in
the nucleus. Actually, we see that ribosomes have two parts, a large and a
Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. Mitochondria are a trans-kingdom enigma. At the molecular level, the components of Human mitochondria are assembled from viruses, bacteria, and other organisms. As such, the organelle we see in human cells today is called a trans-kingdom mixture that doesn't fully resemble any of its ancestors.
genome is built of
16,569 DNA base pairs, whereas the nuclear genome is made of 3.3 billion DNA base pairs. In keeping with its bacterial ancestry, mtDNA
is also circular and multicopy with hundreds to thousands of copies present in
every cell. mtDNA is very genetically compact and encodes only 13 proteins, all
of which are core subunits of the oxidative phosphorylation (OXPHOS) complexes.
These OXPHOS complexes, found only within mitochondria, are unique in human
biology as they are the only cellular structures formed of proteins encoded by
genes from the two separate genomes. The nuclear DNA provides around 90% of the
required proteins for OXPHOS, and the mtDNA provides the remaining 10%.
Remember that the OXPHOS complexes are responsible for ATP production.
Mitochondria are the only organelle to have their own DNA. Mitochondrial
DNA (mtDNA) is more susceptible to damage (including mutations) than nuclear
DNA. The reason for this is many folds. Most likely this is due to a lack
of histones to protect the DNA from damage. The below diagram gives a brief
explanation of histones. Histones package and order the DNA into structural units called nucleosomes. They
act as spools around which the DNA gets coiled and thus a very long strand of
DNA can be fit into a much smaller space. This is demonstrated in the
DNA damage is also caused by the proximity of mtDNA to
Reactive Oxygen Species (ROS) production. We must remember that the
mitochondria are engaged in oxidative phosphorylation which means that they are
using oxygen to produce energy. The by-product of the energy production is the
ROS. Also, mtDNA has limited DNA repair systems and limited proofreading
capacity during replication all of which can lead to accumulated mitochondrial
DNA damage. Furthermore, the mitochondrial DNA is ever changing. When a cell divides, its
mitochondria are partitioned between the two daughter cells. However, the
process of mitochondrial segregation occurs in a random manner and is much
less organized than the highly accurate process involved in nuclear DNA
division during cell replication commonly called cell mitosis. As a result,
daughter cells receive similar, but not identical, copies of their
WHAT REGULATES THE
MITOCHONDRIA? THE SIRTUIN FAMILY OF PROTEINS
Sirtuins are a
family of proteins that regulate cellular health. Sirtuins play a key role in
regulating cellular homeostasis. Homeostasis involves keeping the cell in
balance. Sirtuins can only function in the presence of NAD+,
nicotinamide adenine dinucleotide, a coenzyme found in all living cells. NAD+
is vital to cellular metabolism and hundreds of other biological
processes. Humans contain
seven sirtuins (SIRT1-7) that modulate distinct metabolic and stress response
pathways. Three sirtuins, SIRT3, SIRT4 and SIRT5, are located in the mitochondrion.
The others are found in the nucleus and one in the cytoplasm. The basic role of sirtuins, however, is that they remove
acetyl groups from other proteins. Acetyl groups control specific reactions.
They are physical tags on proteins that other proteins recognize will react
with them. Sirtuins work with acetyl groups by doing whats called
deacetylation. This means they recognize theres an acetyl group on a molecule
then remove the acetyl group, which tees up the molecule for its job. One way
that sirtuins work is by removing acetyl groups (deacetylating) biological
proteins such as histones. When the histones have an acetyl group, the chromatin is
open, or unwound. When the histones
are deacetylated by sirtuins, the chromatin is closed, or tightly and neatly
wound, meaning gene expression is stopped, or silenced. This is not that common
for the Sirtuins in the mitochondria.
Mitochondria regulation is where things get interesting. If we start
manipulating the regulation of the mitochondria then there are a whole host of
conditions from aging to chronic neuro-degenerative conditions which we might
be able to impact. Recent findings have shed light on how the mitochondrial
Sirtuin functions in the control of basic mitochondrial biology, including
energy production, metabolism, apoptosis, intracellular signaling and perhaps
most importantly mitochondrial genesis. The following diagram shows some of
What these Sirtuins
do is help in the generation of cellular energy. As high-energy
electrons derived from glucose, amino acids or fatty acids fuels are passed
through a series of protein complexes (I-IV), their energy is used to pump
protons from the mitochondrial matrix through the inner membrane into the
inner-membrane space. This is referred to as the electron transport chain.
Ultimately, the electrons reduce oxygen to form water, and the protons flow
down their gradient through ATP synthase, driving the formation of ATP from
ADP. Reactive oxygen species (ROS) are a normal side-product of the respiration
process. ROS are essentially free radicals. During cellular stress or damage,
mitochondria release a variety of signals to the cytoplasm and the nucleus to
alert the cell of changes in mitochondrial function. In response, the nucleus
generates transcriptional changes (stimulates certain genes) to activate a
stress response or repair the damage. The main function of mitochondria is to metabolize or
break down carbohydrates and fatty acids in order to generate energy.
In review, ATP
generation occurs within the mitochondrial matrix, though the initial steps of
carbohydrate (glucose) metabolism occur outside the organelle. Glucose is first
converted into pyruvate and then transported into the matrix. Fatty acids on
the other hand, enter the mitochondria as is.
ATP is produced
through the course of three linked steps. First, using enzymes present in the
matrix, pyruvate and fatty acids are converted into a molecule known as
acetyl-CoA. This then becomes the starting material for a second chemical
reaction known as the citric acid cycle or Krebs Cycle. This step produces
plenty of carbon dioxide and two additional molecules, NADH and FADH2,
which are rich in electrons. The two molecules move to the inner mitochondrial
membrane and begin the third step: oxidative phosphorylation. In this last
chemical reaction, NADH and FADH2 donate their electrons to
oxygen, which leads to conditions suitable for the formation of ATP. As an
interesting aside, the optimal ratio of NAD+ /NADH is 700/1. Greater
amounts of NADH lead to aging. NADH is considered a marker of aging. A
secondary function of mitochondria is to synthesize proteins for their own use.
They work independently, and execute the transcription of DNA to RNA, and translation
of RNA to amino acids (the building blocks of protein), without using any
components of the cell.
Another aspect that the Sirtuins control is the control of
Apoptosis. Apoptosis is a cellular process of programmed cell death. This
occurs when the mitochondrial outer membrane allows much more permeability than
normal. This will ultimately commit the
cell to death. Mitochondrial
sirtuins act in synergistic or antagonistic ways to promote respiratory
function, antioxidant defense, insulin response and adipogenesis all of which
can protect individuals from aging and aging-related metabolic abnormalities.
If these cells are not dealt with they might become senescent cells. A
senescent cell is one that should have died but continues to remain alive. The problem
with the senescent cells is that they will release a number of inflammatory
growth factors which can cause havoc in the body.
HOW DO WE KEEP OUR
We have seen the ins and outs of the mitochondrial structure and
function. The question that begs is how do we keep the mitochondria healthy? More and more research
articles demonstrate the foundational importance of optimal mitochondrial
function for health. There is a growing body of research
showing that mitochondrial dysfunction is surprisingly common and associated
with most chronic diseases. The above and below illustrations give us an idea
of how to keep our mitochondria running smoothly. The first illustration shows
some supplements which keep things running smoothly:
The second illustration shows not only specific supplements but also
classes of supplements such as polyphenols (Polyphenols are micronutrients that we get through certain
plant-based foods) and proanthocyanidins (these are chemical
compounds that give the fruit or flowers of many plants their red, blue, or purple
colors). It also stresses some lifestyle factors that can increase mitochondrial
efficiency. The specific supplements that enhance mitochondria function are
evident in the list. Let us talk specifically about some of the polyphenols. They are included in many supplements, though they're also
easy to get in your diet from foods like fruits, vegetables, teas, and spices.
There are more than 8,000 types of polyphenols. A lack of polyphenols isnt associated with specific
side effects. However, they are regarded as lifespan essentials'' for
their potential to reduce the risk of chronic diseases. This is especially true
based on their effects on the mitochondria. Research suggests that supplementation with
pyrroloquinoline quinone, also known as PQQ, can improve the number of
mitochondria in the body while enhancing their functionality. This research
also suggests that effective treatment for many diseases caused
by mitochondrial dysfunction may rest at least partly in this
coenzyme. PQQ is readily found in the soil, so it
makes sense that the best dietary sources are fruits and vegetables grown in
that soil. Fermented foods are rich in these molecules. One of the best sources of PQQ is very dark chocolate.
The above illustration shows some of the main peptides produced by the
mitochondria. Mitochondria derived peptides (MDPs) are a series of peptides encoded by mitochondrial DNA, and have similar
functions to mitochondria. They are new metabolic regulators of human body, and play a
cytoprotective role in maintaining mitochondrial function and cell viability
under pressure. Peptides
are biomolecules comprised of amino acids which play an important role in
modulating many physiological processes in our body. Peptides are
short strings of amino acids, typically comprising 250 amino acids. Amino
acids are also the building blocks of proteins, but proteins contain
more. Peptides may
be easier for the body to absorb than proteins because they are smaller and
more broken down than proteins.
Mitochondria produce numerous small polypeptides from their short open
reading frame (sORF) regions of mtDNA that have significant biological
activity. These include humanin, six small-humanin like peptides, and MOTS-c
(mitochondrial open reading frame of the 12S rRNA type-c), together termed
mitochondrial derived peptides (MDP). MOTS-c is a peptide which is called an exercise mimetic. Exercise
Mimetics are novel ways
of getting the benefits of exercising, without having to exercise. Multiple
studies have demonstrated MOTSc's ability to enhance lipid
beta-oxidation, increase thermogenic brown fat, decrease fat gain on a high-fat
diet, and improve glucose uptake during glycolysis. Various mitochondrial
peptides are produced but their use is not allowed in the USA under the current
regulations. Hopefully, this will change with time.
As time goes on we are discovering more and more about the importance of
the mitochondria and their ramifications to our health lifespan. We see that
methods to boost mitochondria efficiency are varied. But when all is said and
done. Some of the most important factors are exercise especially intermittent
high intensity training, intermittent fasting, a variety of supplements
including NAD. Low levels of oxidative stress such as is produced by
intravenous ozone therapy are also important in the proper function of the
mitochondria. We must remember that mitochondrial decay is inevitable; it cannot be prevented, at least with todays technology.
What is not inevitable is the rate of decay. The mitochondrial rate of
decay is determined by one thing: oxygen efficiency. Perhaps the following
diagram sums it all up:
We see many bad things happen when our mitochondria are not working
Nrf2 is also called the Nuclear factor erythroid 2-related factor 2. NRF2 is a transcription factor that activates over 500 genes. The main reason NRF2 is so highly sought, is because it is a key transcriptional regulator of several antioxidant and anti-inflammatory enzymes. Nrf2 is now recognized to be involved in the cellular response to multiple stressors including foreign substances, excessive nutrient/metabolite supply, inflammation, and the accumulation of misfolded proteins. The Nrf2 protein, known as a transcription factor because of its ability to control genes, is the key component of a pathway (a sequence of biochemical reactions in a cell) that senses and responds to changes in oxidative balance. Nrf2 is one of the body’s major pathways. We need to think of the pathways as the body’s computer software and the cells and organs as the computer hardware. Nrf2, in fact, regulates many hundreds of genes that have nothing to do antioxidant enzymes per se, but rather provide protection from a broader range of stress-related events that are encountered by cells, organs, and organisms, under both normal and pathological circumstances. The Nrf2 pathway is under tight control. When the Nrf2 protein in bound in the cytoplasm it is essentially inactive. The following illustration shows this concept. This illustration is essentially the essence of how the Nrf2 pathway functions. We must remember that Nrf2 is a protein. Proteins, although they are typically confined within the cell or on a cell, have a complicated life cycle. The illustration shows the complicated cycle of the Nrf2 ecosystem. It actually demonstrates its actions in the cell. For example, soon after NRF2 is made by ribosomes in the cytoplasm, it is normally sequestered by KEAP1, which quickly loops the Nrf2 protein with ubiquitin ligase Cullin3 for transport to the proteasome. Here, the ubiquitin is stripped off and NRF2 is degraded and recycled. If all is well in the cell, this process gives NRF2 a half-life of about 20 minutes. Remember, if all is well in the cell Nrf2 is typically not active. Looking at the diagram in a different manner we see that the Nrf2 is held “prisoner” in the cytoplasm. The “prison guard” is called Keap1. If given the opportunity Keap1 will go on and destroy the Nrf2 protein. This is called proteasomal degradation. Given the right conditions (in this case a stress to the body) the Nrf2 protein breaks the stranglehold that the Keap1 proteins maintain. The Nrf2 protein then makes its way to the nucleus where it can eventually react with certain genes and produce certain beneficial compounds. A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway. This explanation is basic but it gives the essentials of how the Nrf2 protein functions. WHAT ARE THE STRESS CONDITIONS THAT STIMULATE THE NRF2 PATHWAY?The Nrf2 pathway senses the need for antioxidant enzymes and regulates their production to maintain metabolic balance. The sensing components of the pathway chemically modify and release Nrf2 so that it may diffuse into the nucleus of the cell where the DNA resides. Once in the nucleus, the Nrf2 will start reacting with a variety of genes found in the DNA of the nucleus. It can then “switch on” or “turn off” the genes it controls (often termed survival genes) to produce the protected state within the cell. Our DNA encodes about 20,000 genes, each representing a “blueprint” for the production of a protein or enzyme necessary for a healthy existence. Each of these “blueprints” requires a regulating control called a “promoter” that determines precisely how much of each product is produced, and under what circumstances. By binding to one specific type of these switch-like promoter regions called the “Antioxidant Response Element (ARE)”, the Nrf2 factor controls the rate of production from hundreds of different genes that allow cells to survive under stressful conditions.NRF2 is part of a group of transcription factors called nuclear receptors. Transcription factors are proteins involved in the process of converting, or transcribing, DNA into RNA. Transcription factors include a wide number of proteins that initiate and regulate the transcription of genes. Once the Nrf2 translocates to the nucleus, it results in the production of Anti-Oxidant Response Elements. There are a number of these elements including Glutathione, Catalase, and a number of other anti-oxidants. We should think of these as endogenous antioxidants. Meaning they are made by the body. These are quite powerful. The next illustration shows more of the whole picture of the Nrf2 pathway. From the Nrtf2 stimulators to the actual response elements to the blocking of the reactive oxygen species (ROS) by the response elements. Ultimately, like many pathways in the body, the Nrf2 pathway targets the mitochondria. The illustration shows certain agents which block the Nrf2 and others which encourage its activation by disabling the stranglehold the Keap1 protein has on the Nrf2 protein. The following is a diagram of transcription factors:The illustration shows how Nrf2 handles the inflammation caused by the ROS. Inflammation is the most common feature of most chronic diseases and complications. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response elements (ARE). These genes produce a large variety of antioxidant enzymes that create a network of protection by neutralizing primary and secondarily generated oxidants and by cleaning up the toxic byproducts they leave in their wake. Also, they help to repair the damage the oxidants have caused. This is especially important for mitochondrial health. Mitochondria help produce free radicals (Reactive Oxygen Species=ROS) and at the same time are very susceptible to their damage. Oxidants such as the superoxide radical (O2-) and hydrogen peroxide (H2O2) are produced by the process of “burning” the foods that sustain us. The Nrf2 pathway senses the need for these antioxidant enzymes and regulates their production to maintain metabolic balance. Several things can upset this delicate balance, the most significant one is aging. Unfortunately, aging slowly tips the balance toward the oxidative side resulting in “oxidative stress.” Disease processes can also result in overproduction of oxidants. Many major diseases associated with aging, such as heart attacks, stroke, cancer, and neurodegenerative conditions such as Alzheimer’s disease also increase production of oxidants thus creating oxidative stress and inflammation. When our immune cells are stimulated they can produce reactive oxidants (O2-, H2O2, OH, and HOCl) to deal with both bacteria and viruses. This can result in the destruction of the viruses and bacteria. But the problem with these compounds is that our otherwise healthy cells get caught in the cross-fire and sustain collateral damage that we see and feel as inflammation. Unfortunately, we have seen this phenomenon in patients with a Covid 19 infection. They get such a vigorous immune response it is called a cytokine storm. Cytokine storms are one of the contributing factors to the high numbers of Covid deaths.HOW CAN WE HELP STIMULATE NRF2?The above diagram shows many of the moving parts of the Nrf2 pathway and its stimulation and resulting end products. In this illustration we see the arch villain of the Nrf2 pathway. This villain is called the NFkB pathway. This pathway is the opposite of the Nrf2 pathway. It is the thermostat of inflammation. It is a very important pathway. We must remember that some inflammation is essential. It is when the NFkB pathway gets over-stimulated that problems arise. Recent research has identified certain processes to be very effective at stimulating our body’s natural mechanisms for creating antioxidants through NRF2 activation. NRF2 activation can be achieved thru exercise, calorie restriction (including fasting) and ingestion of natural nutrients that are NRF2 activators. In our office we have found that intravenous Ozone is a potent stimulator of the Nrf2 pathway. The intravenous Ozone is part of a protocol called the EBO2 protocol. The intravenous Ozone momentarily produces Hydrogen Peroxide. The Hydrogen Peroxide is quickly converted into compounds called Ozone Messengers. These Ozone Messengers result in the stimulation of the Nrf2 pathway. They ultimately help to reduce inflammation. Other in office Nrf2 stimulants include intravenous Curcumin, Quercetin, and Resveratrol. Intravenously, these are very potent Nrf2 stimulants. Since they are given intravenously they become very bioavailable compared to their oral formulations. The question becomes what else can we do stimulate the Nrf2 pathway without a trip to the doctor’s office? We have already mentioned the usual suspects such as exercise, calorie restriction, modified keto type diet etc. However, we can still help to supplement Nrf2 stimulation with some oral compounds. In an ideal world one would first get some supplements intravenously and then proceed with lifestyle changes and oral compounds. Common NRF2 activators include Curcumin which is a widely studied and potent Nrf2 activator. The problem with Curcumin is its bioavailability. Not all Curcumin compounds are the same. Other stimulators include Pterostilbene and its weaker cousin Resveratrol. The problem with oral Resveratrol is also its bioavailability. Other stimulators include Quercetin (from onions) and sulforaphane (from broccoli) and antioxidants found in green tea, chocolate, and other sources. Different nutrients may activate NRF2 by different mechanisms and, when taken together, may be synergistic. I have taken the bull by the horns and designed a supplement which I feel will be unlike anything out there. The propriety blend of ingredients are:Fumaric AcidBrassicaUltracurAlpha Lipoic AcidQuercetinResveratrolPterostilbeneSome of these are well known while others may be new. One of the common threads with these particular compounds is that by and large they have much better bioavailability then their similar counterparts. Brassica is a broccoli derivative. Ultracur is a Curcumin derivative. They both have much higher bioavailability then competing products. One interesting item in this list is Fumaric acid. Fumaric acid is the “Crown Jewel” of this formula. A derivative of Fumaric acid has been approved by the FDA in the treatment of relapsing forms of Multiple Sclerosis. It is also used in the treatment of psoriasis. Currently I am not aware of any Nrf2 supplement blend that is utilizing Fumaric acid derivative mixed with other supplements to stimulate Nrf2. This product should be available shortly. By raising Nrf2 levels, we are able to tap into one of nature’s most powerful mechanisms for the maintenance of good health. Regular consumption of these Nrf2 stimulating foods and supplements may substantially lower many of the health risks of modern living and increase our resistance to many diseases.IN REVIEW WHAT ARE THE PRACTICAL BENEFITS OF THE NRF2 ACTIVATORS?Recent research has found that “NRF2 activation” is very effective at stimulating our body’s natural protective mechanisms including promoting endogenous (natural) antioxidant production. Activation of NRF2 is believed to provide many health benefits including:REDUCING SYSTEMIC INFLAMMATIONLOWERING OF OXIDATIVE STRESS (REDUCING CELLULAR DNA, RNA AND PROTEIN DAMAGE)IMPROVING MITOCHONDRIAL FUNCTION (CELLULAR ENERGY PRODUCTION) ALL ROADS LEAD TO THE MITOCHONDRIANrf2 activation may have a positive impact on chronic inflammation and oxidative stress and so may be useful in the prevention or treatment of many common chronic disease processes including obesity, high blood pressure, reducing the risk of diabetes, cardiovascular disease, stroke, and the list goes on and on. NRF2 activators have been shown to protect the liver in conditions of chronic hepatitis and fatty liver. Let’s look at some more specific conditions that are directly affected by the Nrf2 pathway. Nrf2 ACTIVATION AND OBESITY AND INSULIN RESISTANCEObesity is now thought to be a systemic disease characterized by increased systemic inflammation and oxidative stress. As a consequence, obesity is clearly understood to be a major contributor to the development of hypertension, heart disease, stroke and some cancers. The importance of Nrf2 in obesity and insulin resistance is clearly evident and the potential use of an Nrf2 activator as a treatment method will continue to be an exciting area to advance. Nrf2 ACTIVATION AND PAINNrf2 activation is thought to reduce pain related to many conditions. The muscle pain and fatigue associated with fibromyalgia is believed to respond to NRF2 activation. Nrf2 activation may reduce the central sensitivity associated with many chronic pain conditions including chronic headaches, chronic back pain, and fibromyalgia etc. Nrf2 ACTIVATION AND ADDICTIONMany of the brain’s neurotransmitters and neurochemical processes are impaired in conditions of chemical and behavioral addiction. NRT2 activation may play a role in facilitating restoration of these neurochemical processes and facilitate addiction recovery. Nrf2 ACTIVATION AND STEM CELLS ACTIVATION AND SURVIVALAs a cellular metabolic and stress sensor, Nrf2 is a pivotal regulator of stem cell self-renewal, proliferation, and differentiation. Nrf2 displays cell type-specific and/or stage-dependent impact on stem cell biology in response to various environmental cues. Nrf2 maintain ASCs self-renewal, quiescence, and regenerative capacity while protecting against ASC depletion in response to stress and aging.I suspect this will take on increasing importance in Regenerative Medicine stem cell procedures. We have seen this concept already in organ transplants and rejection. As time goes on, we may depend more on allogeneic sources of stem cells which exhibit immune evasive rather than privileged responses to the immune system.Thanks,Dr. P