We are constantly pushing
the envelope to come up with methods to improve our results clinically. We
think that our new cytokine formula may be such a game changer. Our new formula
makes use of Velvet Deer Antler. But the formula is much different from those
formulas out there both in strength and the formula itself. It is a propriety
The above illustration
represents the growing portion of the antler. Deer Antler Velvet has been used
in traditional Chinese medicine for thousands of years but has recently gained
popularity in Western medicine. Deer antler can enhance immune system function,
improving athletic performance, increasing muscle recovery, enhance sexual
function, improve disease recovery, enhance cardiovascular function, and a host
of other conditions.
Deer Antler Velvet covers the growing bone and
cartilage that develops into deer antlers. The
growing antler contains a number of necessary cells, including fibroblasts,
chondroblasts, chondrocytes and osteocytes. The tips of the antlers begin as
undifferentiated mesenchymal stem cells which are transformed into cartilage.
Later, the cartilage is turned to bone, due to the effects of testosterone.
Deer antler velvet is antler that is still in its cartilaginous stage.
One of the problems with Velvet Deer Antler is the purity and
concentration of the product. Our antler product is sourced from a very
reliable source. Typically, there is a concentration of 1500 mg of velvet
extract per bottle. Honestly, that will have some effects but it is not exactly
what we are looking for. We have sourced a concentration of 4500 mg of Velvet
Deer Antler per bottle. This concentration would not be legal for any
professional athlete and thus we would not use it on them. Typically, these
higher concentrations will help balance hormones and promote tissue repair. In
addition to this we have actually added certain supplements to this very potent
formula. These supplements will increase stem cell efficiency and output from
the bone marrow. This combination is totally unique to our practice and network
and it is proprietary in nature.
WHAT ARE THE MAIN COMPONENTS OF VELVET
The above diagram gives some idea of the many benefits of deer extract. An
important concept that is a common theme of many research papers is that the
combination of all components of velvet antler provides a synergistic effect
that is greater than the total effect that would be achieved by the separate
use of each of its individual constituents. That means that if velvet antler is
broken down into its constituents that are used separately, their combined
effect is significantly less than the effect realized when the nutrients are
provided in the naturally combined form of velvet antler. In summary, the
effect of the complete product is greater than the summed effect of all
Let us take a better look at exactly what is found
in the antler products. Most of the antler product consists of protein. The active ingredients include collagen, lipids,
glycosaminoglycans, minerals, and various growth factors. We will take a look at the major subgroups of
components. The first component to take a look at are the glycosaminoglycans
Glycosaminoglycans are complex carbohydrates. Glycosaminoglycans (GAGs), have widespread functions
within the body. GAGs play a critical role in Regenerative Medicine. They play
a crucial role in the cell signaling
process, including regulation of cell
growth, proliferation, promotion of cell adhesion,
anticoagulation, and wound repair. They are an integral component of what is
called the extracellular matrix. The extracellular
matrix (ECM) is the non-cellular component
present within all tissues and organs, and provides not only essential physical
scaffolding for the cellular constituents but also initiates crucial
biochemical and biomechanical cues that are required for tissue morphogenesis,
differentiation and homeostasis.
Research has shown GAG’s exist in velvet antler in
several forms including:
– a carbohydrate that helps protect and rebuild degenerating cartilage and
is regarded as a potent anti-inflammatory agent
are compounds involved with growth and metabolism of cells and with memory
– is a component of Chondroitin Sulphate and is a major component of
cartilage and synovial fluid
Hyaluronic acid – a
substance that binds cartilage cells together and lubricates joints. It
also acts as a signaling molecule in many biological processes.
– the major structural lipid of most cell membranes
Here is a good illustration of the Extra
Cellular Matrix. It is the substance between the cells.
Antlers grow by endochondral
ossification, the same way that long bones do. A major non-collagenous protein,
proteoglycan, a protein substituted with glycosaminoglycan chains, occurs in
the cartilaginous tissue of antler. While its use in the antler is not
understood, it has been shown that proteoglycan in cartilage, also called
aggrecan, regulates differentiation of chondrocytes and may control calcium
concentration in the growth plates where endochondral ossification occurs. This
may have important implications when we are treating joints with regenerative
More importantly, the next two illustration
shows the ramifications of the Extra Cellular Matrix and repair of various
tissues. We can see why enhancing the Extra Cellular Matrix is so important in
Regenerative Medicine. We can see that these represent the pillars of
regenerative cell therapy. There are few if any other products which have these
effects on the extracellular matrix. This is certainly a huge benefit that
comes with the Velvet Deer Antler product.
The Glycosaminoglycans have a hand in all of
the above repair processes. Most products are only addressing the cellular
portions of repair while the antler products are more comprehensive in their
The next illustration shows how the Glycosaminoglycans
are involved in the new field of tissue engineering. In the case of tissue
engineering we call the synthetic ECM a scaffold.
GROWTH FACTORS: THE CLONES OF WHAT STEM CELLS
When we look velvet antler growth factors we
see a list of who’s who in the growth factor universe. Growth
factors, which are generally considered as a
subset of cytokines, refer to the diffusible signaling proteins that stimulate
cell growth, differentiation,
survival, inflammation, and tissue repair. The major growth factors which are
found in deer antler include Insulin Like growth factors (IGF-1), Bone
morphogenetic growth factors (BMPs), Transforming growth factor family (TGF),
Fibroblast growth factor (FGF), Platelet derived growth factor (PDGF), Vascular
endothelial growth factor (VEGF), Epidermal growth factor (EGF), Interleukins,
and a variety of other factors. When looking at the various growth factors we
realize that this appears to be similar to what is found in a Platelet Rich Plasma
(PRP) product, and for that matter stem cells themselves release. The following
shows some of the major growth factors found in the antler product.
Another aspect of deer antler
deals with its Amino acid contents. Remember that amino acids are natures
building blocks. Amino acids, often referred to
as the building blocks of proteins, are compounds that play many critical roles
in your body. They’re needed for vital processes like the building of proteins
and synthesis of hormones and neurotransmitters. These are broken down to
essential and non-essential amino acids. Another type of amino acid is the free form amino acid. These amino acids aren't joined together with any
other amino acids in a protein 'string'. This allows the
individual amino acids to be instantly absorbed and used by the body without
all the growth factors, the most consequential might be IGF-1. IGF-1 is a
banned substance in the world of professional sports. The precursor of IGF-1 is
Human Growth Hormone (HGH). IGF-1 is actually the active form of HGH. It is
considered performance enhancing. In the smaller doses this is typically not an
issue but in the higher doses we are using this is a problem and across the
board we will not give this formula to any athlete in the high school, college,
or the professional sports arena. Putting this aside, why do we like IGF-1? We
can see some of the benefits below.
more importantly, we need to look at IGF-1 on the basis of cell biology. IGF-1 has been shown
to enhance the migratory response of stem cells. We must realize that the IGF-1
supplied by deer antler is a natural form. It seems to be safer than taking the
synthetic anabolic agents which can have disastrous consequences to one’s health.
The following diagram is somewhat complicated but we see the importance of
IGF-1. It will interact with the stem cell and cause the cell to go on to
repair tissue or differentiate into that tissue.
and the other growth factors can also result in a number of other health
benefits. These extra health benefits may include preservation of a person’s
muscle mass, improving the functioning of the immune system, increasing bone
density thus helping to improve Osteoporosis, a valid treatment for
fibromyalgia conditions, and lastly it may help in weight loss. The bottom line
is that these growth factors are all very important in treating damaged tissue.
This tissue could be a tendon, a joint, or muscle. Remember, with the antler we
are complimenting the growth factors that are supplied by the stem cells and
the Platelet Rich Plasma. Also, by taking these supplements on a daily basis we
continue the repair process. The one small caveat that we follow is that in those
patients who have a history of certain cancers we will typically recommend a
lower dose of the antler product. We should also keep in mind that antler
products also contain small amounts of the sex hormones testosterone and
estrogen. In the right doses these are also important for regeneration.
Another related factor found in the antler is Prostaglandins. They are substances with varying
physiologic effects, acting as a vasodepressor, smooth muscle contraction or
relaxation, inflammation and uterine stimulation. As components of deer antler
velvet, prostaglandins may assist in the capacity of the extract to reduce the
swelling associated with arthritis and injury. They also have physiological
responses in lipid metabolism, as seen in the cholesterol-lowering effects of
deer antler velvet on laboratory animals.
antler contains many different types of amino acids. Amino acids, often
referred to as the building blocks of proteins, are compounds that play many
critical roles in your body. Amino acids are organic compounds composed of
nitrogen, carbon, hydrogen and oxygen, along with a variable side chain group.
Your body needs 20 different amino acids to grow and function properly. Though
all 20 of these are important for your health, only nine amino acids are
classified as essential. These are histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan, and valine. Unlike
nonessential amino acids, essential amino acids are those that can’t be made by
your body and must be obtained through your diet. Another type of amino acid is
a Free-form amino acid. This refers to single amino acid that is already in
a pre-digested form and ready to be used by your body. Some nutritional
products, especially amino acid blends, contain whole proteins and large
peptides (chains of amino acids), which the body must first break down into
smaller peptides and individual amino acids before use. For faster utilization
and better bioavailability, look for free-form amino acids. We can see that all
the various different type of amino acids works synergistically. They all have
WHAT SUPPLEMENTS ARE ADDED TO THE FORMULA TO
ENHANCE THE EFFECTS?
In addition to the Velvet Deer Antler which
provides all the aforementioned compounds. There are a host of other compounds
which enhance the efficacy of the product.
These include a natural matrix of herbs
bounded by research and science to help one’s stem cells become more active and
body supportive. The following compounds highlight these ingredients.
FUCOIDAN – found in the cell walls of certain
seaweed species that is has been used medicinally for a wide variety of health
purposes. Okinawa inhabitants have a diet rich in Wakame
seaweed, which contains the highest concentrations of Fucoidan. Okinawa is also
known for its high concentration of centenarians (people who are at least a
century old), which researchers believe is linked to their fucoidan-rich diet.
The anti-aging effects are associated with Fucoidan's remarkable ability to
facilitate tissue regeneration, immune function as well as improving cell-to-
cell communication. Not only is fucoidan known for its anti-aging effects, it
is also believed to combat cancer, metabolic syndrome and other degenerative
disorders. With stem cell therapy, there is always the risk that the adult stem
cells could migrate to other areas of the body unintentionally. However, the
daily use of fucoidan has been proven to increase mobilization of stem cells to
the appropriate area/ site of injury. Not only can fucoidan point the stem
cells in the proper direction, it has also shown to improve the stem cells'
survival during the differentiation process.
PTEROSTILBENE is a stilbene molecule and demethylated derivative of resveratrol ( it is more bioavailable than resveratrol) that is found in antioxidant-rich
foods like blueberries, cranberries and grapes. These
all help to slow down the aging process. It is an antioxidant that helps fight free
radical damage. It
is known to stimulate a series of pathways in the body called Sirtuin gene
pathways. The sirtuin genes have effects on a variety of other pathways in the
body. Ultimately, the Sirtuins are involved in the regulation of the
mitochondria and subsequent ATP production. Research has shown Pterostilbene protects
against memory loss, high cholesterol, high blood
and even certain types of cancer.
CARNOSINE is an important nonessential amino
acid that helps support brain,
heart, and eye health. It offers antioxidant protection from free radicals and
oxidative stress, boosts endurance, aids in the recovery process, and offers
RASPBERRY EXTRACT, one of the least known, but
yet strongest anti-oxidants that insures chromosomes retain their health and
rebuild themselves to optimum health.
RHODIOLA – an
adaptogenic herb that can elevate your mood and mental stamina, reduce the
stress hormone, cortisol and fight depression due to its
protective effects on key mood neurotransmitters. Rhodiola rosea extracts
have recently demonstrated its anti-aging, anti-inflammation, immuno-stimulating,
DNA repair and anti-cancer effects in different model systems. An adaptogenic
herb helps the body adapt to and resist physical, chemical, and environmental stress.
ASTRAGIN – a 100% natural compound which is patented
and promotes a healthy gut lining reducing inflammation in the intestinal
lining and increasing absorption of nutrients. AstraGin has the
ability to increase the assimilation of important amino acids which increase
nitric oxide levels in the human body, making it the perfect performance
enhancer when taken pre-workout. Higher levels of nitric oxide
result in enhanced blood flow to the muscle which leads to better pumps,
muscular contraction, and improved nutrient transportation. AstraGin also aids
in glucose absorption so having this pre-workout ensures that you have
sufficient energy levels whilst you train.
THE FINAL QUESTION HOW DOES THE ANTLER
PRODUCT GET TO WHERE IT IS NEEDED?
One could have the absolute best formula on paper
but the question is will it work? When we evaluate medications and supplements
a very important aspect to consider is what we call the pharmacokinetics of the
product. This concerns the science of how the drug moves around in the body.
Unfortunately, on paper many compounds seem very promising but in real life are
a failure. The main reason for this is that they cannot be absorbed by the
The mode of absorption of the antler product is what
is referred to as sublingual. This means it is absorbed under the tongue. This
is many times a very effective mode of absorption. It by-passes the gut and
goes directly into the blood stream where it is needed. The components are not
broken down. Also, in the saliva are very small particles called exosomes which
can be considered a rising star in drug delivery. Saliva is a very rich source
of exosomes. Thus, we have a very efficient method of delivering the velvet
components in a safe and reliable manner.
If we were to undertake the task of trying to design
a complete supplement to utilize in Regenerative Medicine and Stem Cell therapy,
Velvet Deer Antler would be at the top of our list. It has most of the
ingredients needed for success. Furthermore, there is a very efficient way to
deliver the goods to the cell where they are needed. Deer antler will not be
the only modality we will use, but it certainly has an important place on our
mantle. We are constantly working to push the envelope and I suspect more advances
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
This is a question that, when I give a lecture to either doctors or the lay public, most everyone gets it wrong. I am not talking about the chocolate one finds in a Hershey’s kiss or chocolate bar, because the problem with these is that they contain too much sugar. I would consider them a very unhealthy food. Ah, but chocolate with no sugar, that is a whole different story. What I would like to do is introduce everyone to the science of chocolate. First off, where does chocolate come from? It comes from the tropical Cacao tree, where it is found in pods. Here we see a picture of the beans that are found in the pod. They are roasted and ground up, then turned into chocolate: When one adds the sugar to these products, that is when the damage occurs. Dark chocolate has both cocoa butter and cacao fiber, both of which science has proven to have health benefits. The cacao fiber is the part of the cocoa bean where most antioxidants are found. This is why dark chocolate with high cocoa solids, and thus more cacao fiber, is considered healthy chocolate. So, now let us get to the science.Dark chocolate is rich in minerals, such as iron, magnesium, and zinc (think anti-viral). The cocoa in the dark chocolate contains some amazing compounds called flavonoids and antioxidants, which have many health benefits. Chocolate is considered one of the best antioxidant foods known to man. The following chart clearly shows this:Antioxidants will neutralize free radicals. Free radicals are highly unstable molecules that are naturally formed when you exercise and when your body converts food into energy. Your body can also be exposed to free radicals from a variety of environmental sources, such as cigarette smoke, air pollution, and sunlight. Free radicals can cause “oxidative stress,” a process that can trigger cell damage. Oxidative stress is thought to play a role in a variety of diseases including cancer, cardiovascular diseases, diabetes, Alzheimer’s disease, Parkinson’s disease, and eye diseases, such as cataracts and age-related macular degeneration. Remember that oxidative stress is one of the major causes of the failure of the immune system (again think virus infections). There is no question that dark chocolate is a superb antioxidant. In a study published in the October 2017 Journal of Community and Hospital Internal Medicine Perspectives, the antioxidants in dark chocolate were found to reduce oxidative stress, which scientists think is the primary cause of insulin resistance and subsequently diabetes. By improving your body’s sensitivity to insulin, resistance is reduced and, in turn, the risk of diseases like diabetes decreases.Also, at the center of chocolate’s health benefits are flavonoids. Most dark chocolate is high in flavonoids, particularly a subtype called flavanols, which are associated with a lower risk of heart disease and a variety of other conditions. As I have already said, some studies suggest chocolate or cocoa consumption is associated with a lower risk of both insulin resistance and high blood pressure in adults. These plant pigments are responsible for many of the health benefits of many fruits and medicinal plants, but chocolate may be a much more sensually pleasing vehicle. In addition, there is evidence that not only is chocolate rich in flavonoids, but that factors in chocolate somehow dramatically increase absorption of these compounds. The key flavonoids are procyanidins, which are similar to those found in grape seed extract, apples, berries, and pine bark extract. There are a few of these flavonoids that garner attention, such as PQQ.PQQ (pyrroloquinoline quinone) restores youthful cellular function and can extend the lifespan. PQQ helps generate and restore mitochondria, especially in aging cells. It allows the mitochondria powerhouses to work more efficiently. Dysfunctional mitochondria contribute to body-wide degeneration. Many of the diseases of aging have one thing in common; namely, they involve mitochondrial degeneration. Remember that mitochondrial degeneration leads to shortening of our telomeres. Shorter telomeres lead to aging. But it turns out PQQ has many other beneficial aspects.A team of researchers from China and Italy found that when PQQ was applied to human cells in culture, it delayed cellular senescence. A growing body of research suggests that reducing cellular senescence may lead to increased health and lifespan. Remember that a senescent cell is a cell that should have died but did not. These cells are like zombies, in that they attack normal cells. A senescent cell will increase inflammatory factors in various areas of the body. There is now a new name for this inflammation; it is called inflammaging. ‘Inflammaging’ refers to the chronic, low-grade inflammation that characterizes aging. We see that inflammation and aging are more or less synonymous. One causes the other to take hold. Recent studies have shown a way that PQQ may be able to slow aging even more, by reducing the activity of certain age-accelerating signaling pathways. The following is a chart shows different foods and the amounts of PQQ they have:Another important bioactive compound found in chocolate is Epicatechin, which is classed as a flavanol. Epicatechin is a natural flavonoid. It has been reported to possess an immense antioxidant effect, which contributes to its therapeutic effect against a handful of ailments. Epicatechin has many different functions. It will increase Nitric Oxide for increased vascularity and blood flow. It will lower cholesterol levels due to its natural antioxidant properties, while improving endurance and insulin sensitivity, regulating blood sugar levels, and stimulating muscle protein synthesis. A very fascinating property of Epicatechin is that it is a myostatin blocker.Myostatin is a type of protein called a myokine, which limits the level of muscle growth. Animals lacking myostatin, either due to a defective gene or because they have been treated with compounds that inhibit production, show huge increases in muscularity. In other words, the brakes on muscle growth are removed by the inhibition or absence of myostatin.Myostatin became famous within the bodybuilding community. It has been considered the holy grail of muscle building. Below is an example of a cow which has a gene that blocks myostatin. If you block myostatin in a human, a similar result will be obtained:A number of supplements have been designed to inhibit myostatin production over the past 20 years, but these have all been discarded as not working well. What is the exact epicatechin/myostatin connection? Research with epicatechin indicates that it increases levels of Follistatin, a special type of protein found in the muscles. Follistatin binds to and thereby inhibits the actions of myostatin in the body. In a nutshell, more Follistatin equals less myostatin, which in turn means more muscle mass and less fatty tissue.A study conducted on males of an average age of 40 showed that approximately 170mg of epicatechin per day, dosed at 2mg per kg of bodyweight, resulted in almost a 50% increase in Follistatin and a 16.6% decrease in myostatin, alongside a strength increase of 7%. In a second study, researchers provided participants with 50-200mg of epicatechin a day and were amazed to find that their Follistatin levels were 250% higher after just 5 days! In a study performed on mice, researchers found increases in nitric oxide and endurance that persisted even in the absence of exercise. In other words, epicatechin supplementation offers bodybuilders the potential for better muscle pumps and endurance even when they are not training. The same may hold true for the average person.As one can see, chocolate is one of the best health foods one can eat. Just remember to leave the sugar out. Do as I do, buy unsweetened chocolate and melt it in the microwave. When it is melted, then add some cinnamon (another great supplement) and Stevia as a sweetener. Sometimes we will add a bit of rum to spice up the flavor. I will typically buy my chocolate in bulk. Also remember that chocolate is much like wine; it can vary in taste by where it is grown and the growing conditions.Thanks,– Dr. P
Calorie restriction remains the surest path to increased longevity and resilience to diseases of aging across many organisms including humans. As an added bonus it is a good to lose those extra pounds especially during the holidays. Calorie restriction seems to affect many aging pathways. If we affect these pathways in a positive manner we can slow down and perhaps turn back the clock of aging. Many of the beneficial effects of calorie restriction appear to be due to modification of specific nutrient-responsive pathways such as the insulin/insulin-like growth factor (IGF-1 which can be considered the active form of human growth hormone) pathway, the target of rapamycin (TOR) signaling pathway, and the NAD+-dependent sirtuin genes. These are the same pathways that control stem cell aging. Remember how our stem cells age is how we age. For example, genetic modulation of any one step in the IGF-1 signaling pathway enhances lifespan in many species. Rapamycin, the first small molecule found to extend lifespan in mammals, works by inhibiting the nutrient-responsive TOR pathway. Finally, the mitochondrial NAD+ pathway stimulates the sirtuin 3 (SIRT3) gene which is required for increased production of ATP and mitochondrial health. These pathways may seem complicated and they are. But realize at the same time they control our fate. What the lay person needs to know about these pathways is they have profound effects on health and aging. Calorie restriction on the surface is great but it is not practical. However, one dietary regimen that mimics healthspan-promoting effects of caloric restriction is the Ketogenic Diet (KD), which consists of high-fat and low-or no-carbohydrates. When glucose is not readily available, fat is broken down by the liver into glycerol and fatty acid molecules. The fatty acid is then broken down further, in a process called ketogenesis. During this process, acetoacetate is the first ketone body that is produced. Acetoacetate is then converted into either Beta-hydroxybutyrate (BHB) or acetone. Acetone is the least abundant ketone body, but it may be produced in higher quantities when you first start the ketogenic diet. This is a reason while some people when first starting the ketogenic diet have bad breath for a short time. As your cells adapt to carbohydrate restriction, BHB becomes the most prevalent ketone body and your brain and muscle cells start using it as their primary fuel. In fact, when you are keto-adapted, ketones can supply up to 50% of your basal energy requirements and 70% of your brain’s energy needs. Let us do a quick comparison between a ketogenic diet and a regular diet which depends on glucose. Glucose is the primary energy source for almost every cell in the body. This is because it can be broken down into energy much more quickly than any other fuel source, and it does this without the help of the mitochondria (the main energy producing component of the cell). Using glucose for fuel, however, comes with some negative effects. What we gain in quickness, we lose in efficiency. During the process of sugar burning more free radicals also called Reactive Oxygen Species (harmful compounds that can cause cell damage these are referred to as ROS) are released and less energy is created than when we use ketones and fat for fuel. The ROS harm cells in many different ways and advance aging on many different levels. On the other hand, Ketones are a more efficient fuel source that inhibits the production of free radicals and reactive oxygen species. This leads to a host of benefits, especially for the brain cells that use ketones instead of sugar for fuel when glucose levels are low. For example, studies done on people with different types of cognitive issues from Parkinson’s disease to epilepsy confirm that using ketones as fuel can improve brain function tremendously. However, the benefits of burning ketones for energy doesn’t stop in the brain. Many other cells like muscle cells also benefit from the use of ketones (more on that later), but you can’t reap these benefits unless you use up your sugar reserves first. A standard Ketogenic Diet efficiently reduces body weight and stimulates liver synthesis of ketone bodies. Ketone bodies are released into the bloodstream and provide energy-efficient fuel to highly oxidative organs, including liver, brain and the heart. In many respects the Ketogenic Diet is similar to calorie restriction in that both produce similar beneficial side effects. There is certainly nothing new about the Keto-Diet. It is mentioned by many people yet few of them have a good understanding of what is really going on. We became more aware of the Keto-Diet when we began working of the new division we are about to launch. This division is called the ADVANCED CELLULAR REPAIR DIVISION. We feel this division will be a game changer on many different levels including anti-aging and success with stem cell procedures. In forming this division, we have learned some of the mechanics of the Keto-Diet and why it is successful in many aspects of health including success with stem cells. I have done a survey of some of the articles on the Ketogenic diet and most of them are parroting the same information. Most of these sites are missing some salient points about the Keto diet. They are not aware of the implications that the ketone bodies have on aging pathways which have a profound effect on our health landscape. The ketogenic diet tries to bring carbohydrates down to less than 5 percent of a person’s daily caloric intake – which means eliminating most grains, fruit, starchy vegetables, legumes and sweets. Instead, it replaces those calories with fat. One myth that needs to be mentioned is that proteins are contra-indicated in a keto diet. Typically, proteins are not a problem. In some circles there is a misconception. Many low carb, high fat advocates believe excess protein can turn into sugar in your bloodstream through a process called gluconeogenesis and knock down your ketone levels. There is no evidence that consuming excess protein will increase glucose production from gluconeogenesis. Gluconeogenesis (GNG) is a metabolic pathway that allows your liver and kidneys to make glucose from non-carbohydrate sources. To clarify, you don’t need to eat any high carb foods to survive, but make no mistake — your body needs glucose and glycogen to keep you healthy (even on ketosis) and it will get this via survival mechanisms like gluconeogenesis. There are a handful of cells in your body that can only use glucose to survive, including red blood cells, kidney medulla (inner part of the kidney), testicles and some parts of your brain. Ketones can cover up to 70% of your brain’s energy needs while glucose from GNG covers the rest. The other organs can’t metabolize ketones at all, so gluconeogenesis provides them with enough glucose to remain healthy. One of the mainstays of the Keto diet is fat. That fat is turned into ketone bodies, which are an alternative energy source: besides glucose derived from carbohydrates, ketones from fat are the only fuel the brain can use in the absence of glucose. Most people are well aware that sugars are inflammatory. When we block glucose metabolism we are having a suppressive effect on inflammatory genes. When we start mentioning genes this should be a tipoff. When you start affecting genes you start affecting cellular pathways. Most people are aware of the benefits of the Keto-diet but when asked why it really works we get a variety of answers. Low glucose is certainly important but what is the overall effect. The following diagram is of the upmost importance in the message we are trying to convey. Instead of Stem Cell Aging Pathways we can easily substitute the name Human Aging Pathways for how our stem cells age are how we age. The Ketogenic Diet seems to have a direct effect on many of these aging pathways. Let us take a look at how the Ketogenic Diet may affect the various pathways. It is well known that caloric restriction extends lifespan. No generally accepted theory has been proposed to explain these observations. However, we now realize that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. Ketone bodies protect neurons against multiple types of neuronal injury and the underlying mechanisms are similar to those of calorie restriction and of the ketogenic diet. The following diagram gives an idea of some of the duties of ketone bodies.The diet’s high fat, low carbohydrate composition reduces glucose utilization and promotes the production of ketone bodies. Ketone bodies are a more efficient energy source than glucose and improve mitochondrial function and biogenesis, increased health span and lifespan and cellular energy production. When we are improving mitochondrial function, we are stimulating the Sirtuin genes which can be found on the first diagram as Sirt1,3, and 6. These same Sirtuin genes are the same ones that are stimulated by vigorous exercise, certain supplements such as Resveratrol, Pterostilbene, NAD, and finally calorie restriction. Thus, we can see the ketone bodies can dramatically affect the Sirtuin genes to help up regulate the production of ATP by stimulating the mitochondria. In many anti-aging circles ATP stimulation is considered one of the holy grails. Ketone bodies as fuel source are more efficient to burn into energy: ketone bodies require only one molecule of NAD+ per molecule of Co-enzyme A, whereas glucose needs 4 molecules of NAD+. As we can see ketone bodies as fuel allow us to have more NAD available. Co-enzyme A is important component in the Krebs cycle. The Krebs cycle is where ATP is made. The more NAD+ available the more ATP that can be produced. But Ketone bodies go beyond being used as a fuel source. They themselves perform signaling activities in a way similar to growth factors. Intriguingly, the ketone body (which is also called BHB) might also be a metabolic intermediary of the benefits of calorie restriction and fasting. Long viewed as a simple carrier of energy from the liver to peripheral tissues during prolonged fasting or exercise, βOHB or Ketone bodies also possesses signaling activities. It therefore joins a small but growing list of metabolic intermediaries that affect gene expression via modifications of the DNA. These changes on the DNA ultimately affect the production of messenger RNA. Messenger RNA than turns on certain genes by giving them commands to produce certain growth factors etc. The following diagram gives us an idea of some of the various effects of ketone bodies in our bodies. Many of the effects we see in the following diagram are the result of Ketone body signaling. We can see that the effects of Ketone bodies are wide ranging. These ketone bodies and their intermediaries may be key links between variations in the cellular environment and the epigenetic changes associated with increased health span and lifespan. Epigenetics, as a simplified definition, is the study of biological mechanisms that will switch genes on and off. Epigenetics affects how genes are read by cells, and subsequently whether the cells should produce certain proteins. Environmental factors such as nutrition dramatically alters cellular metabolism and many also alter the epigenetic regulation of gene expression. Ketones will increase the metabolic coenzyme nicotinamide adenine dinucleotide (NAD), a marker formitochondrial and cellular health. Furthermore, NAD activates downstream signaling pathways (such as the sirtuin enzymes) associated with major benefits such as longevity and reduced inflammation; thus, increasing NAD is a coveted therapeutic endpoint. The literature is now ablaze with information on NAD and earlier this year Time Magazine presented an article calling NAD based supplements a possible true “Anti-aging Pill”. This assumption is not very far off the mark. Based on differential NAD+ utilization during glucose vs. ketone body during energy generation, it appears that a Ketogenic Diet will increase the NAD+/NADH ratio. The more NAD+ available the more ATP that can be produced. ATP production is thought to be a key factor in health and anti-aging. What else do ketone bodies stimulate? Another important pathway in the body is called the NRF2 pathway. The NRF2 (nuclear factor erythroid-derived 2-related factor 2) pathway is the cellular antioxidant system. The Nrf2 pathway has been referred to as the master regulator of antioxidant, detoxification and cell defense gene expression. We can think of Nrf2 pathway as a “thermostat” within our cells that senses the level of oxidative stress and other stressors and turns on internal protective mechanisms. Nrf2 is a potent modulator of antioxidant response and can rapidly target oxidative stressors. Ketone bodies increase mitochondrial glutathione levels by activating the Nrf2 pathway, thus reducing oxidative stress. It modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD+/NADH) which ultimately raises the ATP production. The following diagram shows the NrF2 pathway. We can see the difference between a normal cell and a cell that has suffered from oxidative stress. Ketone bodies are also a stimulator of Autophagy. Autophagy is a necessary part of our survival because it involves killing off pathogens and cells that are potentially dangerous. It involves recycling old, damaged cellular parts into newer ones to keep our bodies free from disease. Below is a diagram that shows the principle of Autophagy.One characteristic of aging is the accumulation of damage, and this is largely due to the failure of autophagy to attain normal functional levels. It can be seen that bringing levels of autophagy to youthful levels can ameliorate aging by clearing out damaged parts of the cell. Cells use autophagy to get rid of damaged proteins and organelles, to counteract the negative effects of ageing on the body. Most anti-aging treatments and protocols have something in common: they all cause an increase in autophagy. Autophagy is central to extending lifespan and to avoiding the diseases of aging. Ketone bodies also seem to have a significant impact in the field of Cellular Senescence. Although senescent cells can no longer replicate, they remain metabolically active and commonly adopt characteristics consisting of a pro-inflammatory growth factors. These cells are capable of doing damage not only on a molecular level but to the entire body. There is much interest on many different fronts in the field of cellular senescence. Lately, senescent cells have been making the headlines several times, as they are a very promising target for medical intervention to delay or even reverse some aspects of aging; while a certain number of senescent cells is tolerable and even beneficial, the accumulation of senescent cells in old age drives several age-related pathologies. My feeling is that the controlling of and eliminating senescent cells may be the next big breakthrough in anti-aging science and other medical fields. We are well aware that senescent cells can have a significant impact on the success of stem cell treatments. The following diagram shows the extent of how senescent cells can cause damage on many different levels.Senescent cells will accumulate growth factors, proteases, and inflammatory factors that disrupt normal tissue function. Senescent cells have long been implicated in aging and decreased success in stem cell procedures. By contrast, cellular quiescence is a reversible state of arrested growth; quiescent cells do not divide, but under the right conditions, they can re-enter the cell cycle and divide again. This state usually occurs when nutrition or growth factors are lacking, and it is thought to be a way that cells can avoid entering a senescent state. The cellular quiescence mechanism also helps cells to preserve stemness and resist stress to their genes. Senescent cells can no longer multiple and divide. The researchers found that ketone bodies can promote cell division and prevent cells from becoming senescent.Although the above diagram is somewhat technical, it shows the difference between a quiescent cell and a senescent cell. We see that the senescent cell has a good deal of damage which has passed the point of no return. We now understand that a ketone body which is produced during calorie restriction or thru the Ketogenic diet will have anti-aging properties. In addition, the researchers found when the ketone body ( BBH also called β-Hydroxybutyrate) binds to a certain RNA-binding protein, this increases activity of a stem cell factor called Octamer-binding transcriptional factor (Oct4) in vascular smooth muscle and endothelial cells (Endothelium refers to cells that line the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood or lymph in the lumen and the rest of the vessel wall). Oct4 increases a key factor against DNA damage-induced senescence. It is thought that vascular aging is one of the root causes of whole-body aging. Another interesting fact is that there seems to be a distinct relationship between ketone bodies and a certain protein that stimulates what is called the P-53 gene. The P-53 gene is also called the tumor suppressor gene. It attacks senescent cells and causes their demise. At the same time, it can cause repair of some damaged cells making them younger. As we can see a diet ketogenic diet can be a very potent force for anti-aging and general health. I have given a quick review of the benefits of this regimen but tried to base it on science. As we can see it has a profound effect on a number of aging pathways in a very beneficial manner. Below is a diagram of a pyramid of the effects of the Ketogenic diet. We see its effects are far flinging.We must remember that success in stem cell procedures is dependent on successful manipulation of the Stem Cell Aging Pathways. I would like to impart one final thought. We need to use some common sense about this diet and “cheat” once in a while. Like I said when it comes to the ketogenic diet we need to use common sense but sometimes common sense is not very common. However, an occasional slice of pizza is not that bad. Thanks ,Dr. P