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

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

Just exactly what is the novel Coronavirus and how is it different from the regular flu? Seasonal flu is an “all human virus”. The DNA/RNA chains that make up the virus are recognized by the human immune system. This means that your body has some immunity to it before it comes around each year. Immunity is obtained in one of two ways. You obtain it through exposure to a virus, or by getting a flu shot. Novel viruses typically come from animals. Usually these viruses only transfer from animal to animal (pigs in the case of H1N1) (birds in the case of the Spanish flu). But once, one of these animal viruses mutates, and starts to transfer from animals to humans then it’s a problem. Why? Because we have no natural or acquired immunity. The RNA sequencing of the genes inside the virus isn’t human, and the human immune system doesn’t recognize it so, we can’t fight it off. Many times, when the virus jumps from an animal to a human it does not have the ability to jump and infect another human. However, when the virus mutates then jumps from a human to a human we have a contagion phase which is what we are now experiencing with the Covid-19 virus. This seems to be the mechanism of the Covid-19 virus that began in an animal market in Wuhan China. Humans have no known immunity to this virus and thus initially no medicines have effectiveness with Covid-19. We now have some knowledge of the Covid-19 virus. The good news is that it still behaves similar to other viruses so we have some basis for treatment. I have covered some of these techniques in some of my other blogs so please excuse the redundancy. WHAT ARE THE COMPONENTS OF OUR IMMUNE SYSTEM Becoming symptomatic from the Covid-19 virus depends on how our immune system responds to the problem. One may only have the sniffles or one could end up in the ICU and be gravely ill. Our immune system consists of two main parts. One is called the innate immunity while the other is called adaptive immunity. The following illustrations show the differences between these two systems. In the first diagram we see the two types of immune systems. The innate system is immunity that is naturally present and is not due to prior sensitization to an antigen from, for example, an infection or vaccination. While adaptive immunity is activated by exposure to pathogens such as the Covid-19, and uses an immunological memory to learn about the threat and enhance the immune response accordingly. The second diagram shows the innate immune response and adaptive immune responses of a Covid-19 infection. The Covid-19 infects macrophages (a form of white blood cell), and then macrophages present Covid-19 antigens to T cells (an immune cell). This process leads to T cell activation and differentiation, including the production of cytokines associated with the different T cell subsets followed by a massive release of cytokines for immune response amplification. WHERE DO THE PROBLEMS START ARISING ESPECIALLY IN THE ELDERLY? Let us discuss immunity more in lay terms. Our immune systems have two sets of defenses against viruses and other pathogens. Our first-line army of cells are called leukocytes (WBCs). They attack invading microbes within minutes to hours, and a second-line force of precisely targeted antibodies and T cells that surge to the battle front as late as several days after. The problems start arising when either the patient has some predisposing condition which weakens his immunity or age is catching up to him. We call the phenomena of aging of the immune system Immunosenescence. With advancing age, the body has fewer T cells, which produce virus-fighting chemicals called cytokines. By puberty, the thymus gland is producing tenfold fewer T cells than it did in childhood. By age 40 or 50, there is another tenfold drop. That leaves the body depleted of T cells that have not yet been programmed to defend against a specific microbe. Fewer such “naïve T cells” means fewer able to be deployed against a never-before-seen microbe such as the Covid -19. These T cells are battle hardened soldiers but they are exposed to an enemy they have no experience with. It was as if our army were to wage battle against aliens. Complicating the problem, there are fewer soldiers that are dealing with attackers that they never experienced before, namely the coronavirus. The body does retain the “memory T cells” that learned to fight attackers in youth, which is why immunization against smallpox and many other viral diseases lasts decades. Even before T cells enter the fray, other cells recognize invaders and dispatch natural killer cells and other soldiers to destroy as many as possible in the first few hours after infection. Then these same front-line cells literally show the virus to T cells, saying in essence, this is the enemy and instructing them to produce virus-killing compounds. But this communication doesn’t work as well as we get older. The instructor cells grow scarce and start giving garbled messages. T cells response is too little and too late. Antibodies are made by B cells, and their decline is less precipitous than the fall-off in T cells. But older B cells can’t produce as much of the antibodies as when they were new. Specifically, they have lower levels of the molecules that rearranges their genome so as to produce never-before-seen antibodies to a never-before-seen virus. THE BOTTOM LINE IS THAT NOT CHRONOLOGICAL AGE ALONE DETERMINES HOW ONE DOES IN THE FACE OF A LIFE-THREATENING INFECTION SUCH AS COVID-19. Having multiple chronic diseases and frailty is in many ways as or more important than chronological age. An 80-year-old who is otherwise healthy and not frail might be more resilient in fighting off infection than a 50-year-old with many chronic conditions. The reason is that the older person may have a younger immune system. OZONE: ONE OF THE ALLIES TO STRENGTHEN THE IMMUNE SYSTEM AND FIGHT THE VIRUS We are very fortunate to have one of the only EBO2 machines available on the east coast. EBO2 stands for Extracorporeal Blood Oxygenation Therapy. This machine is essentially a dialysis machine that utilizes ozone rather than water to perform a “dialysis” procedure. We are not targeting kidney patients but rather a wide variety of the population from professional athletes to the average citizen. Typically, we perform EBO2 to enhance general health and for anti-aging principles. But with the current situation our emphasis has shifted a bit but in the long run the goals are still the same. We are looking for methods to boost our immune system and medical Ozone is one way to do this. There is much scientific literature on the use of medical ozone to help eliminate viruses. For more than 100 years, ozone has been considered a virus killer in the nature. It has been widely used by people for disinfection, sterilization, deodorization, detoxification, storage, and bleaching tanks due to its strong ozonating properties. The virus found in Wuhan and SARS (which respond well to Ozone therapy) virus both belong to the Coronavirus family. Researchers found that the Covid-19 virus is 80% similar to the SARS virus in their genome sequences. It is reasonable to predict that ozone is equally effective in preventing and controlling the new Coronavirus. Most research efforts on ozone's viricidal effects have centered upon ozone's propensity to break apart lipid molecules at sites of multiple bond configuration. Once Ozone interacts with these compounds it produces compounds called Ozonides. Indeed, once the lipid envelope of the virus is fragmented, its DNA or RNA core cannot survive. The following diagram shows this quite well. There are a number of different methods of utilizing medical ozone. However, we only utilize the intravenous method. We utilize a machine called the EBO2 machine. I wrote a detailed blog about the EBO2 machine and its mode of action (blog is found in website stemcellorthopedic.com). The EBO2 has a variety of benefits for the body but for now we will limit out comments to its anti-viral abilities. With EBO2 the entire blood supply passes a number of times thru a dialysis filter after the blood is automatically mixed with ozone gas. Not only are we stimulating the immune system with the ozone but we are also killing viruses in the blood. The unit allows extracorporeal blood oxygenation, ozone exposure and blood filtration. The Ozonides also seem to have a significant effect on cytokine production. Cytokines are messenger molecules that seem to have a significant effect especially on cells of the immune system. The importance of cytokines cannot be understated. Essentially all medical conditions are a result of an imbalance of cytokines. The reaction of the immune cells to the Ozonides causes an increase in cytokine production enabling the body to kill viral cells, kill microbes including the dreaded Lyme’s disease, and potentially cancer cells. Ozone is a potent regulator of the immune system. This means that when the immune system is activated (autoimmunity), ozone will calm it down. Also, when the immune system is depleted (infections, cancer, etc.), ozone will stimulate it. This occurs by ozone’s unique interaction with white blood cells to release immune messenger cytokines. These cytokines are ultimately produced by cells of the immune system. The Ozone therapy stimulates various pathways in the body that specifically deal with oxidative stress and its ramifications. Most of the serious pulmonary and other health problems caused by the Covid-19 virus develop from a phenomenon called a “CYTOKINE STORM”. A cytokine storm occurs when there is excessive immune response between cytokines and immune cells. The symptoms are high fever, redness, swelling, extreme fatigue and nausea, which can be fatal in some cases. The following two illustrations show aspects of a cytokine storm. The second diagram shows the damage that occurs in the body. The goal of our Institute is to prevent the patient from ever reaching the point where they are close to a cytokine storm. This is accomplished by a sort of balancing act. If the immune system is stimulated too much the storm will develop. There is too much inflammation which is causing oxidative damage which results in tissue damage. Many infections including the Covid-19 virus overwhelm the body by the production of Reactive Oxygen Species (ROS) which are very similar to free radicals. The reactive oxygen species are the contributors of oxidative stress which lead to various diseases and disorders such as cardiovascular disease, cancer, aging, and various neurodegenerative diseases. In the case of Covid-19 we see mainly pulmonary and kidney problems. The best way to prevent oxidative damage is to fight it with powerful anti-oxidants. This is where EBO2 therapy shines. Most battles in the body are a result of a tug of war in various pathways in the body. One very important pathway is called the NRF2 pathway (nuclear factor-erythroid 2-related factor 2). The NRF2 pathway is the master regulator of antioxidant, detoxification and cell defense gene expression. It regulates over 600 genes involved in cellular protection and anti-oxidant defenses. It modulates numerous genes responsible for cognitive processes, inflammatory responses, rebuilding tissue, immune system response. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. Furthermore, NrF2 stimulates another pathway called the NQ01 pathway. The Nq01 is intimately involved with NAD production and insures a proper NAD/NADH ratio. of antioxidant, detoxification and cell defense gene expression. Considering the significant impact of the Nrf2 pathway on the pathophysiology of both host cell and virus, Nrf2 modulators may be able to serve as a promising supplement for viral diseases by therapeutic modulation of virus-induced oxidative stress in the near future. Well the future is here in that EBO2 is a potent stimulator of the NrF2 pathway. The NrF2 pathway seems to inhibit another very important pathway called the NF-κB-r pathway. NF-κB has long been recognized as a point of convergence of inflammation, aging and disease. Remember, all diseases including the Covid-19 virus really either get eliminated or get a foothold by their effects on various pathways in the body. Below is an illustration of the NrF2 pathway and its’ relationships to other pathways. As we can see, the EBO2 machine and Ozone can work in two distinct ways. First, there is the ability to actually kill viruses in the body by destroying their protective coating. Secondly, and perhaps more importantly they remove the “stranglehold of oxidative stress” on the immune system thus allowing it to more efficiently perform its job. One final note on Ozone therapy. On March 24 the following letter was written. “After evaluating possible insights, the letter signed by Dr. Luigi Bertinato, Head of the President's Scientific Secretariat, says that since the proposal to use oxygen ozone "is supported by clinical centers experienced in the treatment of viral pneumonia, the Istituto Superiore di Sanità considers it appropriate that the treatment itself can be carried out, after acquiring the patient's informed consent. Essentially, the Italian government feels Medical Ozone seems to have great promise in the treatment of Covid19. NAD, AN IMMUNE BOOSTER Another very important aspect of EBO2 is the effect it has on NAD production and subsequent stimulation of the Sirtuin genes. We take this one step further by supplanting the NAD produced by the EBO2 with intra venous delivery of NAD. Mounting evidence points to NAD+ as one of the major modulators of immuno-metabolic circuits, thus regulating immune responses and functions. Recent studies show impaired host NAD+ metabolism during chronic infections and inflammation, suggesting NAD+ replenishment as an avenue to ameliorate deleterious inflammatory responses. Besides playing key roles in various cellular enzymatic reactions and signaling pathways, mounting evidence suggests that NAD+ dictates the host’s innate and adaptive immune responses. Thus, the evidence is fairly convincing that NAD+ may have significant beneficial effects on our immune system. For this reason, it is one of our weapons in boosting immunity. NIH has a clinical study that has been completed but not yet published to study NR's positive effects on healthy peoples innate immune systems. There are two types of immune systems the body uses to combat viral infections. Let us review it one more time. The first is the innate system which offers a first line of defense by preventing pathogens from taking hold if they enter the body. This is what can prevent you from being infected in the first place. The second system is the adaptive system where once a pathogen has taken hold, the body develops a specific response to the pathogen. This includes both antibody responses as well as cell-mediated responses. Boosting NAD has shown benefits in both the innate system as well as the adaptive system. As adults get older both immune systems decline along the same time frame that NAD declines in the body. The bottom line is that the NAD has direct effects on the Sirtuin Pathways which seem to influence most of the other pathways in the body. We must also remember that NAD+ is of prime importance in the production of ATP. All cells need ATP as a source of energy. NAD+ itself is also used by various enzymes to repair DNA damage. Here is an illustration of NAD benefits. GENERAL INTRAVENOUS THERAPY At most of the med-spas, when you ask the employees about how various IV therapies work they state that it improves the immune system and makes one feel better. But when pressed as to how it improves the immune system they are hard pressed to give an answer. We give the answers below. We have a wide variety of intravenous methods to boost immunity. I will mention a few of them. We have already mentioned NAD given via an IVroute. NAD has far ranging impacts on various functions in the body including our immune system. Another type of intravenous therapy is called Myers cocktail. Myers’ Cocktail is a formula of intravenous vitamins and minerals that was pioneered by the late Dr. John Myers, MD. The “Cocktail” includes magnesium, calcium, B-vitamins (including B12), and Vitamin C and is given by a slow IV push or slow infusion to achieve concentrations of nutrients that are not obtainable with oral administration. It appears that this cocktail will hopefully increase one ability to respond to immune challenges. The vitamin C is especially important. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. We always hear Vitamin C is helpful but what is the real mechanism of action? Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils (WBCs), and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial and viral killing. We have other similar intravenous therapies that seem to boost immunity. These are more or less variations of the Myers cocktail but seem to have more effects on the immune system. Another type of intravenous formula is called Immune Boost. This is somewhat similar but yet different than Myers cocktail. One thing they all have in common is Vitamin C. The following shows the multitude of Vitamin C benefits. We must realize that when you are sick you need a good bit more Vitamin C. The best benefit from Vitamin C is when it is in your blood, hence IV route. There are some studies in China that seem to support the use of Vitamin C in Covid 19 virus. Will Vitamin C cure the Covid -19 probably not, but it should be able to alter its course for the better. I have a diagram on the various aspects Vitamin C has upon the body’s immune system. Another aspect of our IV therapy involves Glutathione. This powerful antioxidant is one of most protective molecules in the human body. There are two different forms of glutathione: reduced glutathione (GSH, or L-glutathione), which is the active form, and oxidized glutathione (GSSG), the inactive form. As GSH patrols the cellular environment and puts out oxidative “free radical” fires, it becomes oxidized itself and inactive, thus turning into GSSG. Fortunately, inactive GSSG can be recycled back into the active GSH form, thanks to an enzyme called glutathione reductase. When this enzyme is overwhelmed and too much oxidized GSSG accumulates (as compared to the active GSH), your cells become susceptible to damage. Glutathione is such an important antioxidant to the human body that a scientific study suggests that the abundance of glutathione in the cells can help predict the life expectancy of that human. Glutathione has also been shown to be a powerful anti-inflammatory agent because it inhibits the production of most inflammatory cytokines. Glutathione can also help repair cells that were damaged by radiation, pollutants, stress, infection, and a range of other ailments. Surprisingly enough, glutathione can also slow the process of aging in the cells. As we age, our cells begin to lose their ability to self-repair and to produce strong antioxidants. Increasing our intake of glutathione can help replenish or replace the antioxidants lost from aging and slow down the aging and deterioration of our cells and aid in the self-repair of the cells to prolong their functionality and lifespan. As an antioxidant, glutathione removes oxygen radicals from the body which can harm other cells in the body and cause disease and deterioration. While vitamins C and E are also antioxidants, glutathione has the added benefit of already living within each of your cells allowing it to perfectly placed to do its job. One problem with glutathione is that it has a poor oral absorption rate. It is well absorbed when given via an intravenous route. WHY IS OUR IV THERAPY UNIQUE? What will make our IV therapy unique is that we will add some unique products to our IV formulas. We will include some cytokines in very small dosages. For instance, one of these is GCSF. GCSF is called granulocyte colony stimulating factor. GCSF acts in a similar method as to a medicine called Neupogin. Neupogin is a medicine given to patients who have taken chemotherapy and their blood count became low. It especially helps to build up their white blood cell count (WBCs). Remember, WBCs fight viruses. We will give the GCSF in a few different ways. We have an oral form that is absorbed under the tongue, we can deliver it via a patch which utilizes a weak electrical current and is called iontophoresis. Lastly, we will give some low dose intra venous therapy. Another addition is IFNγ, or type II interferon. It is a cytokine that is critical for innate and adaptive immunity against viral, some bacterial and protozoal infections. IFNγ is an important activator of macrophages. The importance of IFNγ in the immune system stems in part comes from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFNγ is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by CD4 Th1 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops. Again, we can deliver this a few different ways to the patient. The last product I would to mention is one called Immunexx. Like some of the other cytokines, this is a compound made by the Canadian company we are working directly with called Viatrexx. Immunexx is an interesting compound. It has a number of interesting components that seem to be significant immune boosters. Again, this can be delivered to the patient in a number of different ways. We also produce our own blend of cytokines that seem to promote healing etc. We have been using this for uyears with excellent success. MEDICATIONS AND SUPPLEMENTS We certainly recommend good multi-vitamins. However, we have some specific recommendations when it comes to immune boosting. Luckily, we have access to some of these. VITAMIN C 5g/day (25mg/pound N-ACETYLCYSTEINE 600mg/day GLUTATHIONE 500mg/day L-LYSINE1000mg/day VITAMIN D 5000IU/day ZINC is a mineral that's commonly added to supplements and other healthcare products like lozenges that are meant to boost your immune system. This is because zinc is essential for immune system function. Zinc is needed for immune cell development. A deficiency in Zinc significantly affects your immune system's ability to function properly, resulting in an increased risk of infection and disease, including pneumonia. Oral NAD 600mg/day ELDERBERRY SYRUP 1 tsp/day UMCKA (Pelargonium sidoides) An herbal remedy of a species of South African geranium, Umcka plays a role in the production of a specialized protein, called cytokines, that may protect the body’s cells from viral infection. BETA GLUCANS effects are caused by stimulation of both cellular and humoral immune reaction resulting in lower viral load. RED MARINE ALGAE: seems to have antiviral properties. Dosages depends upon the brand. CURCUMIN. Curcumin is the main active compound in turmeric. It has powerful anti-inflammatory properties, and animal studies indicate that it may help improve immune function LICORICE contains more than 20 triterpenoids and nearly 300 flavonoids. Triterpenoids are widely found in plants. It is found that triterpenoids have a variety of pharmacological activities including anti-inflammatory, anti-diabetic, anti-cancer, regulation of immune function, etc. Among them, only two triterpenes, GL and GA have been reported to have antiviral effects. They can weaken virus activities by inhibiting virus gene expression and replication, reducing adhesion force and stress, and reducing HMGB1 binding to DNA. Medicinal mushrooms have been used since ancient times to prevent and treat infection and disease. Many types of medicinal mushrooms have been studied for their immune-boosting potential. Over 270 recognized species of medicinal mushrooms are known to have immune-enhancing properties. I am sure that I can more to the list but this should suffice for now. The above is in addition to the supplements that one takes to maintain general health. For instance, mine would include Neo-40 (nitric oxide supplement), Resveratrol, Pterostilbene, Green tea extract, and StemXcell, and some other supplements. SENSECENT CELLS AND SENOLYTIC AGENTS Cellular senescence is a phenomenon characterized by the cessation of cell division. A senescent cell is one that should have died but did not. It can act like a zombie in the body. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. Aging and senescent cells have a great impact in both innate and adaptive immune systems. This is a process known as immunosenescence which I have already spoken about. Immunity declines during aging, as shown by the increased susceptibility to infection by both previously encountered and new pathogens and by the decreased efficacy of vaccination. We are aware that induction of senescence alters leukocyte, and specifically T cell, function. An effective immune response against viral infections depends on the activation of cytotoxic T cells that can clear infection by killing virus-infected cells. So, the bottom line is if we can eliminate some senescent cells it would probably make our immune systems function better. Remember, our immune system is responsible for removing senescent cells. If we can take away some of this burden than our immune system will function more efficiently. However, it is important to retain some senescent cells. I strongly advise people to take at least an over the counter senolytic agent on a temporary basis. Make sure these compounds contain Fisetin, Quercetin, and Piperlongumine. In our office we use some very powerful senolytic agents. These include quercetin and a medication which we are using off label. PRESCRIPTION MEDICATIONS The FDA has issued an emergency authorization of the anti-malaria drug Hydroxychloroquine for Covid-19 virus. Although the evidence seems to be anecdotal, there does appear to be efficacy. I ordered the dosages for myself and my family. I have also included a dosage of a Z-pack (Azithromycin). I would recommend the Hydroxychloroquine to be taken if one tests positive or if one has symptoms of Covid -19 virus. The dosage should be two tabs twice a day on the first day followed by one tablet twice a day for five days. The Z pack should be started at the same time. Another aspect of medications includes certain peptides. Peptides are naturally occurring biological molecules. Peptides are found in all living organisms and play a key role in all manner of biological activity. Some of the peptides we will utilize include Thymosin alpha-1 and Thymosin Beta 4. Thymosin alpha-1 is the most recommend peptide for immune stimulation. This should be used as a treatment adjuvant and a prophylactic aid that can help with many conditions beyond viral illness! Most will dose it at 450mcg daily. Thymosin Beta-4 stimulates Natural killer (NK) cells which are essential for defense against tumors and virus-infected cells. These cells are activated in by INF-Gamma. IFN-gamma is activated by IL-18 which TB4 upregulates. Thus, TB4 has been studied for many immune related diseases. One other peptide to consider is LL-37. This is a peptide made by mesenchymal stem cells. It is a very strong bactericidal and viricidal agent. There are some biologics that are currently under consideration. Remdesivir is a broad-spectrum antiviral drug that interferes with a virus’ ability to replicate. It was originally developed to treat Ebola but had only limited success. However, a study from 2017 showed that remdesivir was able to successfully stop SARS and MERS — sister coronaviruses to the new strain — in both human cells and animal models. In February, Chinese scientists found that remdesivir successfully blocked the novel coronavirus, SARS-CoV-2, from replicating in human cells. Lopinavir and ritonavir, an antiviral drug combination was initially developed to treat HIV, but it turns out it works on other viruses as well. The drugs are given together because lopinavir breaks down very quickly on its own, and it lasts longer when paired with ritonavir. Similar to chloroquine and remdesivir, scientists discovered in 2004 that lopinavir was moderately effective at stopping the original SARS virus from replicating in human cells. When given in combination, lopinavir and ritonavir also helped treat SARS in human patients. There is also talk of utilizing some of the biologics that are used for autoimmune diseases. A simple and promising treatment which is being considered is the use of the Contrad anti-inflammatory patches (AI). I use these in my stem cell practice on a daily basis. These patches are revolutionary. They are registered with the FDA. They have very powerful anti-inflammatory agents which can be of great importance in the face of pulmonary problems resulting from a cytokine storm. These are patches which will have the gel placed on a patch and then they are placed on the lung and left for about 6-8 hours. The gel contains penetrating molecules which drive the cytokines down deep. There are currently some studies going on the Milan Italy using these patches. From what I am hearing there seems to be some promising results. PERIPHERAL BLOOD STEM CELLS This is a type of stem cell coming from the patient. It is found in the blood and is prepared in a propriety method. What is of significance here is that these cells seem to make the immune system younger and healthier. Remember, the reason why some people exposed to the virus never get ill is because of their immune system. As I said earlier a healthy immune system is a healthy patient. One major effect that these cells have on the immune system is that they will make the telomeres of the immune system cells longer. Remember, the telomeres are found at the end of the DNA strand. The shorter the telomere the less effective the cell would be in performing its tasks. Longer telomers will most of the time either prevent or ameliorate many different health issues including viral infections by virtue of making the immune system healthier. Remember what we said about immunosenescence. Short telomeres cause senescent cells to form. So, these peripheral blood stem cells can certainly be a potent weapon in the battle against the Covid-19 virus. The process is quite simple. First, on day one we stimulate the bone marrow to release large number of the cells into the circulation. On day two the blood is taken from the patient and is processed. On day three the cells are given back to the patient and hopefully perform their magic behind the scenes. WHAT HAVE I DONE, WHAT AM I DOING, WHAT WILL I DO??? I am faithful in doing my exercises everyday I practice the precautions recommended by the CDC including wearing a mask and gloves whenever leaving home. Also follow social distancing I take my supplements including a number on the list. It is about a handful every day. I will make sure that I take extra CURCUMIN. I have recently received IV vitamin C, NAD, and GLUTATHIONE. I will probably get more of the same. It is probably not a bad idea to get IV Vitamin C on a weekly basis for the next few weeks I have done an EBO2 and Peripheral blood stem cell treatment within the last few weeks. I intend to give myself another EBO2 in the near future. A few weeks ago, I took my senolytic agents so we are good there. If I become symptomatic or I suspect an exposure. I will take Hydroxychloroquine and a Z pack, take higher doses of vitamin C and NAD including intravenous delivery. I will perform another EBO2. I will take Berberine to help control my blood sugar. If I become symptomatic in chest area will use the AI patches. The results from Milan seem to be very promising CUT OUT ALL SUGARS!!!! All they will do is add to the inflammation of the immune system. I will go on the oral cytokine formula that we give to most of our patients Also, it would not be a bad idea to pray. HOW ABOUT IMMUNITY?? How well a person’s immune system remembers SARS-CoV-2 is called immune memory. It helps our bodies avoid reinfection by a bug we’ve had before. Immune memory influences the potency of life-saving treatments and vaccines. For now, in people who have had the Covid-19 virus, it appears unlikely that they will get it again. But, and this is a big but, we cannot say for sure. When a pathogen breaches the body’s barriers, the immune system will churn out a variety of immune molecules to fight it. One subset of these molecules, called antibodies, recognizes specific features of the bug in question and mounts repeated attacks until the invader is purged from the body. Antibodies can also be a way for clinicians to tell if a patient has been recently infected with a given pathogen, even when the microbe itself can no longer be detected. COVID-19 packs a stronger punch than the common cold, so antibodies capable of fending off this new coronavirus may have a shot at lingering longer. Typically, the more severe the disease, the more resources the body will dedicate to memorizing that pathogen’s features resulting in a stronger and longer lasting the immune response. Complicating matters further is the biology of SARS-CoV-2 itself. Viruses aren’t technically alive. They contain genetic instructions to make more copies of themselves but they lack the molecular tools to execute the steps to reproduce. Therefore, they must hijack living cells to complete the replication process. After these pathogens infect cells, their genomes (genetic material) often duplicate sloppily, leading to frequent mutations that persist in the new copies. Most of these changes are inconsequential or lead to revolutionary dead ends. Occasionally, however, mutations will alter a viral strain so substantially that the immune system can no longer recognize it and subsequently sparking an outbreak even in populations that have seen a previous version of the virus before. Viruses in the influenza family are the poster children for these transformations which is in part of why scientists create a new flu vaccine every year. WHERE DOES THE ANSWER TO CONQUERING THE COVID-19 LIE? These next two diagrams most likely hold the solution to defeating the Covid-19 virus. The solution to the virus lies in one or more of these pathways. These diagrams represent the stem cell aging pathways. REMEMBER HOW STEM CELLS AGE IS HOW WE AND OUR IMMUNE SYSTEM AGES. MORE IMPORTANTLY, I HAVE A SAYING I USE IN MY LECTURES “CELLS NOT DOCTORS HEAL PATIENTS”. We can manipulate the cells in methods I have already mentioned but ultimately, THE CELL WILL HEAL THE BODY. No one knows for sure which pathways are involved. Most all of the techniques and procedures mentioned in this report will affect certain of these pathways. The answer is right before our eyes in these two diagrams. These diagrams represent the cause and solution to the Covid-19 virus. How these pathways are stimulated can mean health or sickness!! Manipulate these pathways and you will manipulate the immune system. Some food for thought!! This is another scheme of the pathways. The next diagram gives a view of the various subpopulations that are affected by the Covid-19 virus. A FINAL COMMENT OR TWO. We have been practicing telemedicine for a number of years now so we are still a phone call away to discuss concerns and questions. IN THE BIT OF LEVITY, there is a good song that seems to sum up times: THIS IS THE OLD CHUCK BERRY SONG The title of it is “RIDDING AROUND IN MY AUTOMOBILE, LISTENING TO THE RADIO, WITH NO PARTICULAR PLACE TO GO” Seems to be a good song for the times where we have stay at home orders with no place to go !!!! Stay safe and practice CDC RECOMMENDATIONS and consider some of these other options. Please realize that these statements have not been evaluated by the FDA. THANKS, - DR. P

Below you will find the previously recorded video from Dr. Purita's Facebook Live event on 3-20-20 in addition to his PowerPoint presentation on the subject of COVID-19.

The Coronavirus has certainly made a splash throughout the world. This blog is not to take the place of what has already been recommended by the CDC. Common sense precautions should be used but the problem is that common sense is usually not very common! Some of these precautions include hand washing, washing down surfaces with an appropriate disinfectant, wearing a mask if you are sick, and staying out of circulation if you potentially may have been exposed to the virus. Let us get a few things straight. The Coronavirus is not like Ebola where many relatively healthy people would succumb to the disease. On the contrary, the people who have a compromised immune system are much more prone to develop serious health issues with Covid-19 rather than the typically healthy individual. There have been some reports that the virus has mutated already. This could be good or bad. Its virulence could change for the worse. If we see that the virus has changed and has become more of a threat to the healthier population what are some steps we can take to treat the Covid-19 using some of the tools of Regenerative Medicine? Will an increase in seasonal temperatures contain the infection? Only time will tell. Well first off there seems to be some evidence that high dose Vitamin C and D and some other supplements may be of benefit in the prevention and treatment of the Covid-19 virus. To enhance their effect, some of these could be delivered via an intravenous route. My good friend and supplement Guru, Reid Eckert, is high on the use of Red Marine Algae and also Beta Glucan. This is what Web MD has to say about Beta Glucan “Healthcare providers sometimes give beta-glucans by IV (intravenously) or by injection into the muscle to treat cancer and to boost the immune system in people with HIV/AIDS and AIDS-related conditions. Beta-glucans are also given by IV to prevent infection in people after surgery”. There is good scientific evidence that Beta Glucans stimulate various cells of the immune system includes cells called macrophages and another called natural killer cells. As far as Red Marine Algae records indicate that red marine algae, a form of Traditional Chinese Medicine (TCM) dates back to approximately 300 B.C. As is the case with many such products it was recommended for a variety of conditions but modern science does support a possible role in the treatment of viral infections. This seems pretty straight forward Perhaps three other important measures to be considered include exercise, keeping our gut bacteria healthy, and reducing the senescent cell load on our immune system. To be immunologically fit you need to be physically fit. Exercise has to be part of your daily regimen. Also realize that our gut bacteria program our immune system. A variety of probiotics will enable our gut bacteria to keep our immune system running efficiently. The last consideration is the use of senolytic agents to kill senescent cells. Senescent cells are cells that should have died but did not. These cells put a burden on the entire body by secreting certain “bad” growth factors. These bad growth factors could have a deleterious effect on the immune system. When we get past these simple measures things become a bit more interesting and cutting edge. At this time, I am not sure how a stem cell (with the possible exception of one type) would work in the case of the Covid -19 virus. The delivery would have to be most likely an intravenous route. Being cognizant of regulatory issues there may be limited choices here in the USA. Putting regulatory issues aside one could use cells derived from adipose tissue. This is performed by breaking down adipose tissue with an enzyme. The resultant product can then be given intravenously. Again, regulatory issues aside, if one is able to obtain fresh umbilical cord stem cells (not the products that are typically sold to physicians in the United States) that might be an option. The problem that we have with the IV of delivery is that the stem cells usually get trapped in the lungs rather than go to different parts of the body. The life span of these cells is fairly short. Most of the cells get phagocytized by a cell called a monocyte and subsequently produce a cell called a T-reg cell. T-reg cells can be a double edge sword. T-reg cells can reduce inflammation which is certainly tremendously important if we have a virus which is destroying lung tissue as is found in an active Covid-19 infection. However, the price of reducing inflammation is that we are also reducing anti-viral activity. However, as the stem cells perish they may release some of their cytokine peptides. One very important cytokine peptide is called LL-37. LL-37 is a host defense peptide (HDP). It is made by a variety of cells including mesenchymal stem cells (MSCs). Another name for LL-37 is Cathelicidin. Some other compounds produced by MSCs are called Defensins and Hepcidins. But for brevity I would just like to discuss LL-37. LL-37 is a compound that will kill both bacteria and viruses. As a matter of fact, most women have LL-37 to thank for not developing sepsis during their menstrual period. Realize that menstrual blood is rich in MSCs which will typically release LL-37. The LL-37 will crush any bacterial growth preventing any infection. The Hepcidins and Defensins seem to also work against both bacteria and viruses. LL-37 has been shown to be highly effective in preventing viral attachment to cell However, as I stated there are some big drawbacks with using MSCs. As we said earlier there are some tendencies that might allow the MSCs to reduce the effectiveness of anti-viral treatments. The scientific literature on the subject of MSCs and viruses is not conclusive. Perhaps here is a good statement from one of the articles “The interplay between MSC and virus can be defined as double-edge sword. Upon encountering virus, MSCs appear to produce deleterious effects and act as viral transmitters which may subsequently worsen a therapeutic efficacy. Thus, the safety of MSCs administration should be ensured by screening the presence of viruses in donor and recipients. Since the clinical experiences of MSCs and viral infection remain largely unknown, more future studies addressing the behavior of MSCs in infectious environment would better explain this story”. These statements appear to show the good, the bad and the ugly of using MSCs. Now one possible solution to the double edge sword is to bypass the MSCs and use some of their anti-viral peptides that are available. This is what we call recombinant DNA. Recombinant DNA technology has applications in health and nutrition. In medicine, it is used to create pharmaceutical products such as human insulin. Recombinant DNA technology requires the use of molecular scissors called restriction enzymes, which cut DNA at specific sequences. Eventually bacteria reproduce the compound. Some of these peptides such as LL-37 are readily available on line. LL-37 has been shown to be highly effective in preventing viral attachment to cells. Used in several virus studies and has been anecdotally reported to work well with respiratory tract viruses. Other ones will include Thymosin alpha-1 (TA-1) – Thymosin alpha-1 is the most recommend peptide for immune stimulation. This should be used as a treatment adjuvant and a prophylactic aid which can help with may conditions beyond viral illness. Another peptide is Thymosin Beta-4 (TB4)- Natural killer (NK) cells stimulant. NK cells are essential for defense against tumors and virus-infected cells. These cells are activated in by INF-Gamma. IFN-gamma is activated by IL-18 which TB4 upregulates. TB4 has been studied for many immune related diseases. The following diagram gives an idea of the mechanism of action of TA-1. The bottom line is that we want to stimulate the immune system in a manner so that it will attack viruses while at the same time limiting collateral damage. The diagram below is an illustration of how some of these peptides seem to work especially TA-1. WHAT OTHER UNIQUE METHODS MIGHT BE USED? OZONE MAY BE ONE OF OUR BEST ALLIES There is much scientific literature on the use of medical ozone to help eliminate viruses. For more than 100 years, ozone, considered a killer of virus in the nature, has been widely used by people for disinfection, sterilization, deodorization, de-toxification, storage, and bleaching thanks to its strong ozonating properties. According to results of an experiment on how ozone kills SARS virus conducted by the Chinese national P3 laboratory headed by Professor Li Zelin, ozone is effective in killing the SARS virus inoculated on green monkey kidney cells, realizing a killing rate of 99.22%. The virus found in Wuhan and SARS virus both belong to the coronavirus. Researchers found that the novel coronavirus is 80% similar to the SARS virus in their genome sequences. It is reasonable to predict that ozone is equally effective in preventing and controlling the new coronavirus. Most research efforts on ozone's viricidal effects have centered upon ozone's propensity to break apart lipid molecules at sites of multiple bond configuration. Once Ozone interacts with these compounds it produces compounds called Ozonides. Indeed, once the lipid envelope of the virus is fragmented, its DNA or RNA core cannot survive. Ozone can be administered in different ways; topically, through the ears, into the bladder, vagina or rectum, via an ozone steam sauna and through different IV applications. However, we only utilize the intravenous method. We utilize a machine called the EBO2 machine. I wrote a detailed blog about the EBO2 machine and its mode of action (blog= stemcellorthopedic.com). The EBO2 has a variety of benefits for the body but for now we will limit out comments to its anti-viral abilities. I can best describe EBO2 technique as a dialysis which utilizes medical ozone gas instead of water. The entire blood supply passes a number of times thru a dialysis filter after the blood is automatically mixed of ozone gas. Not only are we stimulating the immune system with the ozone but we are also killing viruses in the blood. The unit allows extracorporeal blood oxygenation, ozone exposure and blood filtration. The Ozonides also seem to have a significant effect on cytokine production. Cytokines are messenger molecules that seem to have a significant effect especially on cells of the immune system. The importance of cytokines cannot be understated. Essentially all medical conditions are a result of an imbalance of cytokines. The reaction of the immune cells to the Ozonides causes an increase in cytokine production enabling the body to kill viral cells, kill microbes including the dreaded Lyme’s disease, and potentially cancer cells. These same cytokines can have a profound positive effect on many auto-immune diseases. As it turns out most autoimmune diseases are a very specific imbalance of cytokines. Ozone is a potent regulator of the immune system. This means that when the immune system is activated (autoimmunity), ozone will calm it down. Also, when the immune system is depleted (chronic infections, cancer, etc.), ozone will stimulate it. This occurs by ozone’s unique interaction with white blood cells to release immune messenger cytokines. These cytokines are ultimately produced by cells of the immune system. The Ozone therapy stimulates various pathways in the body that specifically deal with oxidative stress and its ramifications. One very important pathway is called the NRF2 pathway (nuclear factor-erythroid 2-related factor 2). The NRF2 pathway is the master regulator of antioxidant, detoxification and cell defense gene expression. It regulates over 600 genes involved in cellular protection and anti-oxidant defenses. It modulates numerous genes responsible for cognitive processes, inflammatory responses, rebuilding tissue, immune system response. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. Considering the significant impact of the Nrf2 pathway on the pathophysiology of both host cell and virus, Nrf2 modulators may be able to serve as a promising supplement for viral diseases by therapeutic modulation of virus-induced oxidative stress in the near future. Well the future is here in that EBO2 is a potent stimulator of the NRF2 pathway. There are also other pathways that Ozone will stimulate. The EBO2 treatment takes about one hour to perform and it causes no discomfort to the patient other than inserting the intravenous needle. PERIPHERAL BLOOD STEM CELLS This is a type of stem cell coming from the patient. It is found in the blood and is prepared in a propriety method. What is of significance here is that these cells seem to make the immune system younger and healthier. Remember, the reason why some people exposed to the virus never get ill is because of their immune system. As I said earlier a healthy immune system is a healthy patient. The following is a slide from one of my lectures. The article above shows that the telomers of the cells of the immune system increase in length after a treatment of the peripheral blood stem cells. An increase in the length of the telomere means that he cell has gone back in age. It has gotten “younger” and most likely healthier. When all is said and done a healthier and younger immune system will most of the time either prevent or ameliorate many different health issues including viral infections. So, these peripheral blood stem cells can certainly be a potent weapon in the battle against the Covid-19 virus. WHAT WILL I DO??? First off, I will not panic! I will certainly take precautions as recommended by the CDC concerning hygiene such as hand washing etc. I will continue to do my hour and a half of vigorous exercise each and every day. I will continue to take a hand full of supplements every day. These include Vitamins D and C, NAD, and another of other supplements. I like the NAD (actually, Nicotinamide Riboside) due its effect on the sirtuin pathway. We now know that the Sirtuins seem to be intimately involved with the immune system. I will take IV versions of NAD from time to time. Every few months I will take senolytic agents to decrease the senescent cell load on my immune system. Remember senescent cells are those cells that should have died but did not. These cells cause a host of medical problems. Currently I take Quercetin and Dasatinib every few months. However, there are numerous senolytic agents on the market which are over the counter. Just make sure it contains Fistin and black tea extract among other things. I typically do peripheral blood stem cells every six months and an EBO2 treatment every six months for now. If I find out that I have been exposed to the virus than I will get more aggressive and immediately perform an EBO2 treatment, followed by peripheral blood stem cells, red marine algae, beta glucan, a Meyers cocktail containing extra vitamin C, extra probiotics, and LL-37 peptide. At least, I did everything I possibly could and based it on science. I am sure there are other suggestions out there and I am more than happy to hear them. Thanks, Dr. P

The Cupid and Venus shots are for sexual wellness in men and women, respectively. This blog will discuss the Cupid ShotTM. In the near future, we will have a blog concerning the Venus shot. The Cupid Shot for Erectile Dysfunction (ED) is totally unlike the typical PRP shot for Erectile Dysfunction. Cupid is the Roman god of desire, erotic love, and attraction. Without warning, he selects his targets and forcefully strikes at their hearts bringing confusion and irrepressible feelings. The Cupid Shot will usher in a paradigm shift in the treatment of ED with Regenerative Medicine. When the usual treatment modalities in ED fail, many times the patient is given a PRP injection. The PRP is rich in growth factors, which may help the problem of ED. Most ED problems result from a lack of an adequate blood supply in the region of the Penis. The lack of blood supply can be caused by many different reasons including diabetes and a host of other conditions. The Penis is most susceptible to changes in its microvasculature given the fact that Penile arteries have the smallest diameter of the vascular network. We must understand that the vasculature system can self-renew itself. This self-renewal is supplied by a continuous supply of circulating endothelial progenitor cells. There are a number of growth factors that come into play when dealing with ED. These growth factors are present in a PRP product, but typically more prominent in bone marrow aspirate. The significant difference between bone marrow aspirate and PRP boils down to the progenitor cells. These are the cells that help establish a blood supply. There are very few of these cells in a PRP preparation. On the other hand, bone marrow aspirate is fairly rich in these progenitor cells. Therein lies one huge difference between a PRP preparation and Bone marrow preparation. We have used some propriety methods for the not only obtaining, but also processing of the both the PRP and Bone Marrow. This gives a totally unique set of weapons to improve the symptoms associated with ED. We are trying to correct more upstream issues connected with ED. It all boils down to circulation or lack of it. We are acutely aware that bone marrow has shown great promise in cardiac problems by increasing vessel producing endothelial cells. The bone marrow serves as a continuous supply of circulating endothelial progenitor cells (EPC) for the systemic vasculature. We have methods to increase the numbers of cells released by the marrow, as well as methods to increase the cells when harvesting bone marrow. PRP, on the other hand, has little in the way of stem cells to stimulate the circulation. This represents the second major difference between bone marrow aspirate and PRP. Not only will we use biologics from the patient, but we will utilize signaling molecules that will help to correct long standing problems. These biologics are also called cytokines. They give direction to the cells, influencing their genes to subsequently influence their surroundings, ultimately increasing vascularity. Thus, we can see that in the Cupid shot we are addressing the vascular problems with a three-prong approach. First, we will increase the number of circulating progenitor cells released from the bone marrow. This is accomplished by some specific supplements, specific cytokine formulas delivered by both an oral and a transdermal route. This will hopefully result in more robust numbers of cells released from the bone marrow, allowing for a richer harvest. Second, we are employing a propriety approach to bone marrow aspirate by utilizing a hybrid marrow product. This marrow product consists of both a centrifuged and non-centrifuged component. Both marrow components are subsequently subjected to photo modulation. Realize, also, that the bone marrow aspirate contains PRP. There are other aspects of our treatment, such as various supplements. We have vetted these supplements from different sources. These supplements will sustain and enhance the process. We feel that this multi-prong approach can deliver success that is not seen with typical ED treatments. With our program for treating ED, like all of our treatment programs, we pride ourselves on being on the cutting-edge of the cutting-edge. Thanks, - Dr. P (The Cupid Shot and the Venus Shot are registered trademarks of Joe Purita, MD and Institute of Regenerative Medicine. Unauthorized use is prohibited by law.)

Our flagship clinic in Boca Raton hosts the Advanced Cellular Repair Division. One goal of this division is to offer personalized protocols of cellular restructuring and the repair of some of the afflictions of aging. This restructuring, which is based on the principles of basic science, cellular and molecular therapy, and anti-aging medicine, attempts to do a reset on many degenerative problems. Health is not just the absence of illness; it is the state of integral well-being and systemic balance, which depends on certain genetic, psychological and environmental factors, and in great measure depends on how we absorb and make efficient use of nutrients and eliminate wasteful toxins, in order to seek an adequate internal balance. We are very pleased to announce that we now have one of the first units for EBO2 therapy in the USA. This represents another quantum leap for our practice and our patients. EBO2 allows for the reduction of chronic inflammation and creates a watershed of positive impacts on the quality of life and performance of its patients. We must remember inflammation is the mother of all disease. EBO2 stands for Extracorporeal Blood Oxygenation and Ozonation. This seems like a complicated phrase. If we break it down we get an idea what it really means: Extracorporeal means outside the body. Oxygenation mean just what it says; putting oxygen into an area. Finally, ozonation means adding ozone to an area. The ozone aspect may have some people confused. What exactly is ozone? Ozone has been widely used for medical purposes for years in Europe, Russia and more recently in the United States. Most of us have all experienced Ozone. If one takes a walk after a thunder storm you will many times smell a very pungent “clean" odor. What has actually happened is that the power of electricity in lighting has caused oxygen molecules to bond and form ozone, or as it is sometimes called, "triple oxygen." The following diagram explains the concept of how Ozone is made from an electrical current. An Ozone generator works in a very similar way. This ozone is very important for our environment. It can protect us from many bad things, such as radiation and a host of other potential problems. Scientists have been intrigued by Ozone for decades, as for its possibilities for medicinal purposes. Much of the original research was done in Germany and Russia. The ''EBO2'' is a modern high-volume blood gas exchange unit for the treatment of 5-7 liters of blood with medical ozone. The unit allows extracorporeal blood oxygenation, ozone exposure and blood filtration. The process filters blood in a unique way by using the integrated diffusing membranes within the filter fibers to trap lipids and proteins, which are in excess in the venous blood supply. The EBO2 unit is considered the world's most advanced medical ozone therapy. Perhaps another way of looking at the process is to describe it as dialysis with ozonation. The EBO2 machine re-circulates all of a patient’s blood (5-7 liters) over a period of 60-90 minutes. The EBO2 treatment with medical ozone removes some of the extra inactive proteins which can lead to autoimmune related disorders, it also separates fats, cholesterol, heavy metal toxins, and diseased dead cells. It traps and removes these impurities and fats with a special patented filtration system. Most other methods of advanced Ozone therapy involve what is called Autohemotherapy. The following is a diagram of this technique: Until recently, this was considered the state-of-the-art method of delivering Ozone to the body. It is now very much outdated. All these other methods typically may add ozone to a portion of the blood, but are doing nothing to remove the offending agents found in the blood. In the above method, blood is added to an IV bag that is typically filled with a saline solution and an anti-coagulant (blood thinner). Ozone is then injected into the bag containing the blood. Certainly, this method can help, and at one time was considered a safe state-of-the-art treatment. Fifty years of safe use on millions of patients has a lot of weight. The drawback to this technique is its effectiveness. Not to sound redundant, but with the EBO2 method we are separating toxic blood waste products that the body cannot eliminate by conventional means, such as heavy metals, petroleum byproducts, inorganic substances, cellular waste and fat macroparticles. Removing these reduces their inflammatory effects. which are related to aging and chronic diseases. We are removing by filtration the ozone-oxidized leftover garbage of dead microbes, diseased cells and detoxified by-products that are filtered out of the blood via the external filters. The waste products are not sent back through the liver, kidney and lymph systems to irritate and perhaps weaken the body further, as occurs in all other ozone methods. Perhaps the best description of the EBO2 method is to call it Recirculatory Autohemo Perfusion followed by filtration. There are some other methods of delivering Ozone to the body, but by-and-large these are not that effective, and some are fraught with potential problems. It should be mentioned that, although the EBO2 machine is similar to dialysis, it should be considered a modified form of dialysis utilizing Ozone as a cleansing agent rather than water. Also, as an added bonus, the EBO2 procedure is also removing a compound called Beta 2 Microglobulin. Beta 2 Microglobulin is a very sneaky compound. It is a cell protein which is associated with many different cancers and inflammatory diseases. There seems to be a relationship between Beta 2 Microglobulin levels in the blood and these diseases. We are happy to report that the EBO2 technique seems to remove an impressive amount of this protein. It appears as a foam in a container. During my own treatment with the machine, the container needed to be emptied a few times, unlike other patients who needed more frequent emptying. HOW DOES OZONE THERAPY WORK? How does Ozone itself work? Ozone in a biological system will immediately interact with the double bonds found in amino acids and lipids (fats) to form compounds called peroxides. Bonds are what holds biological compounds together. It is the action of these peroxides that actually cause the biological effects seen with Ozone. These peroxides are collectively called ozonides. It should be mentioned that ozonides form what is called an ionic bond. To not get too technical, the ionic bond that Ozone forms is a magnetic type of bond. Magnetic bonds do not produce free radicals. So, unlike hyperbaric oxygen and other oxidative therapies, Ozone therapy does not produce a substantial number of free radicals. Remember that free radicals are responsible for DNA mutations, mitochondrial damage, and a host of other situations which can lead to degenerative conditions. Oxygen utilization appears to be the single most important factor concerning aging and degenerative diseases. Ozone therapy has a very critical influence on Oxygen utilization. When cells use oxygen, they are actually producing the critical compound call ATP. ATP supplies all the cells with energy. The influence that Ozone has on oxygen utilization boils down to one very critical factor, namely NAD (Nicotinamide Adenine Dinucleotide). I have written a number of blogs on NAD that you can refer to for more information. Ozone is a powerful mitochondrial stimulant. The mitochondria are the energy source for every cell in your body. The fundamental cause behind all chronic illness, from diabetes to heart disease, cancers, chronic fatigue, etcetera, is decreased mitochondrial energy production. NAD is critical to many cellular functions. Without NAD, the body is not able to produce ATP. Every cell requires ATP. Furthermore, certain DNA repairing enzymes are large consumers of NAD. When these enzymes do not function properly, DNA damage accumulates, and with this accumulation comes many bad problems. We must also realize that NAD is a rate limiting substrate for DNA replication, which subsequently effects all of protein synthesis. One of the most important cellular reactions in the body is as follows: OXYGEN + NADH ---> NAD + Water + Energy ATP NAD is the oxidized form and NADH is the reduced form of Nicotinamide Adenine Dinucleotide. Thus the more NAD present, the more efficiently oxygen is being utilized. As I have written in some of my other blogs, also of critical importance is the NAD/NADH ratio in addition to the amount of NAD in the cell. NAD production in the body is a very complicated process. The body uses a number of different pathways to produce NAD, and subsequently ATP. This is where Ozone therapy shines! As we age we have difficulties with oxygen utilization. Ultimately, this affects the NAD/NADH ratio, ATP production and the list goes on. Remember that Ozone therapy forms compounds called Ozonides. Ozonides are formed when Ozone comes in contact with lipids and amino acids. These Ozonides penetrate the cell membrane and oxidize NADH back to NAD, helping to maintain an optimal NAD/NADH ratio. Many people think that the only importance when dealing with NAD is the amount of NAD in the cell. The diagram below will show just how this principle is so important in the field of Bioenergetics. We now know that cellular energy, or lack of it, leads to many degenerative conditions. Conversely, restoring energy to more normal levels may help ameliorate many of these same degenerative conditions. The following diagram is a good synopsis of the NAD/NADH relationship: The Ozonides also seem to have a significant effect on cytokine production. Cytokines are messenger molecules that seem to have a significant effect especially on cells of the immune system. The importance of cytokines cannot be understated. Essentially, all medical conditions are a result of an imbalance of cytokines. The reaction of the immune cells to the Ozonides causes an increase in cytokine production, enabling the body to kill viral cells, kill microbes -- including the dreaded Lyme’s disease, and potentially even cancer cells. These same cytokines can have a profound positive effect on many auto-immune diseases. As it turns out, most autoimmune diseases are a very specific imbalance of cytokines. Ozone is a potent regulator of the immune system. This means that when the immune system is activated (autoimmunity), ozone will calm it down. Also, when the immune system is depleted (chronic infections, cancer, etc.), ozone will stimulate it. This occurs by ozone’s unique interaction with white blood cells to release immune messenger cytokines. These cytokines are ultimately produced by cells of the immune system. Another important aspect of Ozone therapy is the effect it has on oxidative stress. Oxidative stress occurs when various free radicals and a variety of other offending agents exceed the body’s anti-oxidant enzymes systems. Ozone therapy will stimulate the activity and production of all antioxidant buffering systems in the body. Ozone increases antioxidant protection more than any other therapy. Most patients with chronic illness have depleted antioxidant capability. The Ozone therapy stimulates various pathways in the body that specifically deal with oxidative stress and its ramifications. One very important pathway is called the NRF2 pathway (nuclear factor-erythroid 2-related factor 2). The NRF2 pathway is the master regulator of antioxidant, detoxification and cell defense gene expression. It regulates over 600 genes involved in cellular protection and anti-oxidant defenses. It modulates numerous genes responsible for cognitive processes, inflammatory responses, rebuilding tissue, immune system response, and inhibiting cancer production and preventing its spread. We can see that the NRF2 pathway has very far ranging effects. Another very important pathway that is directly stimulated by Ozone therapy is called the NF kappa Beta (NFkB) pathway. Nuclear factor kappa-β is a transcription factor (turns on or turns off genes) that is the “master switch” for inflammation. Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB), resulting in an inflammatory response and tissue injury via the production of a variety of offending agents including cytokines. However, moderate oxidative stress activates Nrf2 pathway. Nrf2 then induces the transcription of antioxidant response elements (ARE). These are very strong anti-oxidants. Transcription of ARE elements results in the production of numerous antioxidant enzymes. One such enzyme is called as NADPH-quinone-oxidoreductase (NQO-1). NQO-1 is also called the longevity gene. It is very helpful in maintaining the proper NAD/NADH ratio. This ratio is about 700/1. Another ARE element comes from glutathione, which is considered a master anti-oxidant. The following diagram illustrates some of these effects from these pathways. We can see the various beneficial effects achieved. Another very important aspect of Ozone therapy is its production of Nitric Oxide (N0). Nitric oxide is a wonder drug having far reaching effects. These effects range from lowering blood pressure to increasing stem cell release into the circulation, to destroying bacteria and viruses in the system. As we age, the levels of NO in our body diminishes. NO is a very important signaling molecule in the body. Thus, we can see that the effects for the EBO2 are far reaching. Again, there may be many clinics that are performing primitive Ozone therapy, but very few are doing an EBO2 treatment. Remember most of these clinics are only treating a small portion of the blood, typically no more than 500CCs, while we are treating the entire circulatory system (at least 10 times more). Furthermore, we are filtering out many of the bad demons that I have previously addressed. The EBO2 is a world class treatment for those who want to increase their physical performance, re-establish their body balance, strengthen their immune system and auto defense capacity. This a treatment protocol designed for both healthy individuals in addition to those having a variety of health issues. EBO2 is a method to increase performance in a legal way in professional sports, and the same holds true for the weekend athlete. We are not just wanting to increase lifespan, but also increase health span. Health is not just the absence of illness; it is the state of integral well-being and systemic balance which the EBO2 technology brings forth. In a nutshell, EBO2 re-circulates all of a patient’s blood (5-7 liters) over a period of 60-90 minutes for treatment with medical ozone to remove extra inactive proteins which can lead to autoimmune related disorders, it also separates/removes fats, cholesterol, heavy metal toxins, and diseased dead cells while trapping and removing impurities and fats in a special patented filtration system. EBO2 can help in the reversal of auto immune related diseases, inflammatory diseases and arthritis, as well as Lyme disease and its related co-infections. The following photos were taken from the EBO2 website: The statements in this article have not been evaluated by the FDA. Furthermore, this EBO2 procedure is not intended to "diagnose, treat, cure or prevent any disease."

Many in the chiropractor community wish to be involved in Regenerative Medicine. Unfortunately, there are some that are exposing themselves to a variety of potential problems both legally and professionally by choosing to use umbilical cord products, amniotic products, and exosomes. First off, these products typically do not have any stem cells -- yet these same doctors are touting the fact that the product does have stem cells. That leaves the Chiropractic physician open to claims of fraud. Secondly, the FDA has stated unequivocally that if these products are to be used in the United States, they need either a Biologics license or an Investigational new drug application. Both entities are costly and time consuming, and currently none of these products have this classification. Thus, these products are in violation of the existing FDA guidance. Fortunately, we now have We now have SIGMOLECS® Technology, which is an alternative that can allow the Chiropractor to become involved in Regenerative Medicine in keeping with the current guidance regulations and local state chiropractic boards. I, myself, have used this technology for the past several years on thousands of patients with superb results and essentially no side effects. SIGMOLECS technology is an advanced chemical profiling through structural assembling of key molecules, mostly proteins and peptides, that form actuated molecules. It accomplishes this by specifically improving their bio-activity in solution and in vivo by increasing their transmembrane penetration. This creates precise specificity of action, particularly in intracellular signaling. This is essentially the method that the body uses to heal itself and is the essential basis of Regenerative Medicine and cytokine therapy. SIGMOLECS molecules induce signals to key amino acid sensors that govern gene expression of amino acid metabolism that then trigger specific physiological and metabolic activity. The nuts and bolts of Sigmolecs molecules is quite simple. Sigmolecs® molecules are really like microchips carrying the information we want to program into the patient. So, once designed and synthesized Sigmolecs are put into a proprietary gel that delivers them trans-dermally, while at the same time causing essentially no reaction in the skin. We must also be cognizant of the fact that if you don’t have the right delivery system for your clinical application, even the most potent medicine will not work. These SIGMOLECS molecules are structured according to key amino acid sensors to trigger specific regenerative tasks. This is done by grafting bioactive peptides or amino acid (AA) sequences onto a source molecule, usually a natural source of protein like Soy protein or Collagen peptides. This becomes the template for the Sigmolecs molecule that will be structured to have very specific bioactivity. Many of the mini-proteins found in plants are desirable for this work because of the resistance they contribute to enzymatic degradation, and their native structure provides a chemical template conducive to various sequence designs. Overall, this allows the synthesis of specific bioactive peptides while silencing signals and gene expression encoding undesirable processes; such as, proteinase secretion and expression of associated catabolic cytokines. Sigmolecs® molecules are configured and assembled to mirror highly specific intracellular signaling factors. These are the same factors that stem cells and other regenerative cells utilize to accomplish repair of damaged tissue. They are essentially clones of what the body produces. SIGMOLECS designer molecules are part of the delivery package; that is, the gel carrier. It contains Sigmolecs® Technology in that it designs scaled molecules that can easily penetrate the skin and enter deep tissue. The molecules are fashioned according to sequences that are ‘skin friendly’ and can facilitate navigation through cell membranes. For example, when using native peptides from suis collagen peptides the molecules provide a chemical template to structure therapeutic specificity in a repair combination. The basic gel amalgam provides structural molecules conducive to crossing skin and cell barriers, and in this sense, is a completely functional product that is both a carrier and a therapeutic gel in one. This gel enables the transfer of large molecules and solutes through cutaneous channels that normal dermal formulation or patches could not deliver. It allows penetration of large molecular weight molecules to cross the Stratum Corneum, deeply penetrating the epidermis and dermis, reaching vascular and cellular targets through tissue permeability akin to injection, but without any invasive needling. There are two different type of products which are available in gel monodoses to be used with a patch. The first gel monodose is called the AI (ANTI-INFLAMMATORY) monodose which is upgraded to code for IL-10 and IRAP. These two entities are considered master anti-inflammatory cytokines. The raw material used to design the therapeutic Sigmolecs P3 AI gel is Soybean protein. This plant contains several small proteins that are already anti-inflammatory in nature, but more importantly, that are conducive to structural modification. Many drugs have been fashioned from plant molecules; most are proteins such as cytokines. Many come from Tobacco plant cell cultures, such as IL-2, IL-4 and the famed Neupogen otherwise known as G-CSF! Even Human Interferons have been successfully produced from plants, and many more human synthesized cytokines originate from plants. The Anti-Inflammatory sequence provides vascular support, regulation of blood flow and platelet function, and very importantly, inhibition of inflammatory cytokines specifically, IL-6, IL-8 and TNF. It mediates the inflammatory response to prevent and reduce edema and pain while also contributing considerable analgesic effect without invasive pain procedures. The RG REGENERATIVE MONODOSE GEL invokes cell differentiation especially to chondrocytes and keratinocytes. The raw material used to design the therapeutic SIGMOLECS® P3 RG gel is suis collagen. The peptides extracted from this source naturally regulate neutrophils especially in stem cell procedures while at the same time they stimulate and induce mobilization of transplanted adult stem cells. The SIGMOLECS® combination of structures in the P3 RG gel regulates the cell cycle particularly by signaling resting phase cells to migrate to areas of repair. It combats oxidative reactions in synovial fluid while stimulating chondrocytes to repopulate decellularized tissue at the site of injury. It also provides the extracellular matrix with signals, such as those that mimic hematopoietic cytokines, which reinforce procedures such as PRP and stem cells treatments. Furthermore, in Regenerative Medicine, the use of RG gel monodose post regenerative therapy will enhance the treatments by sustaining stem cell niches enhancing the success of clinical treatments. Moreover, suis collagen peptides, in particular, are structured cleaner than other types of collagen which allows for a larger spectrum of sequencing for specific therapeutic action. These actions include sequences that mimic growth factor signaling such as Insulin Like Growth Factor (IGF) and Fibroblast Growth Factor (FGF.) The suis collagen peptides have more affinity for human synthesized growth factors than other collagen sources. The RG gel is particularly good to apply after a stem cell treatment. It will enhance treatment protocols by providing the regenerative cytokine signals and also provides the needed elements to the extracellular stem cell niche. It signals repair pathways while inhibiting TNF-override that often occurs during repair processes. Please notice that the opinions in this article are solely my own professional opinions intended for professionals only. Thank you, Dr. Joseph Purita These gel monodoses are now available for sale in the U.S.A to health care providers. For details please contact: Bob Colucci, at PuRxCell Phone number: 561-350-4465 Email: [email protected]

NAD stands for Nicotinamide Adenine Dinucleotide. It is an essential coenzyme that you can’t live without. The above diagram is an excellent synopsis of what the ramifications are to having low levels. If you ask me are we trying to scare you about low levels the answer is a resounding YES. Low levels will result in death and unfortunately a not a healthy life on the way to one’s demise. One significant aspect of NAD is the effect it has upon a certain group of proteins/genes called the Sirtuin proteins. The Sirtuins are a family of proteins that play a role in aging by regulating cellular health. They're responsible for critical biological functions like DNA expression and other aspects of aging. However, sirtuins can only function in the presence of NAD+, nicotinamide adenine dinucleotide, a coenzyme found in all living cells. NAD is an essential building block during energy production. The energy in this case is ATP. We lose up to 50% of our NAD levels between the ages of 40 and 60. It would seem simple enough to just replace the levels to keep things working at an appropriate level. Just exactly what other aspects does NAD seem to affect in the body? One answer is that it effects the mitochondria. The mitochondria are the power houses of the cell. Consider the mitochondria as batteries for the cells. This diagram shows this concept of the cell battery. Ultimately, the decline in mitochondrial function causes us to age. A prominent theory of aging holds that decaying of mitochondria is a key driver of aging. Recently (Oct 2019), researchers at Yale Univ. proposed that a metabolic dysfunction of the mitochondria as responsible for Alzheimer’s disease. There are now two competing hypotheses are currently proposed to explain the cause of Alzheimer’s: the first is focused on the accumulation of amyloid-beta protein in the brain as the primary cause; while a second and more recent hypothesis proposes that metabolic dysfunction, specifically a dysfunction of the mitochondria, is responsible. This speaks volumes about the importance of healthy mitochondria. NAD+ deficiencies and subsequent mitochondrial problems are thought to lead to a multitude of problems stemming from heart disease to various neurological conditions. We can see that when the “batteries” become run down bad things start happening. We go from healthy to chronic illness and cancers! It seems that the tissues that have the most mitochondria such as the heart and brain are most prone to degenerative conditions. Much of the pioneering work concerning NAD+ comes from the research of David Sinclair of Harvard. Dr. Sinclair first shed light on the compound called Resveratrol. It was thought that Resveratrol stimulated the Sirtuin genes. It was discovered that these genes were turned on by exercise and some other entities that have scientific background of slowing down aging, namely starvation, calorie restriction etc. It is felt that Resveratrol mimics starvation and exercise. It appears now that another compound called PTEROSTILBENE which is found in blueberries and grapes may have a better effect than Resveratrol because it is more bioavailable. Resveratrol and Pterostilbene are important for daily supplement intake. In 2013, Sinclair further reported scientific studies that demonstrated NAD fuels the activity of this same group of proteins as Resveratrol, namely the sirtuin proteins/genes including SIRT 1 and 3. NAD has two general sets of reactions in the human body. The first is that it functions by turning nutrients into energy as a key player in metabolism. The second aspect is that NAD works as a helper molecule for proteins that regulate many biological activities. When it functions as a helper molecule it is called a Coenzyme. Without Coenzymes little would happen and we would essentially die. Here is a diagram of the Sirtuin family. As can be seen there are seven members of the Sirtuin family. Although the field of Sirtuin research has gone through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of Sirtuins as an aging/longevity regulator. Sirtuins are a fascinating family of enzyme/proteins/genes. Sirtuins have been called the guardians of the genome. They are instrumental in regulating cellular health and ultimately aging. We can see that some of the Sirtuins are found in the mitochondria while others are found in the nucleus. While a third group is found in the cytoplasm of the cell. It is the communication of these various Sirtuins with each other that control the health, numbers and function of the mitochondria. Remember that the mitochondria have a downstream effect on most cellular functions. An emerging consensus from recent studies is that sirtuins may act as metabolic sensors, using intracellular metabolites such as NAD to modulate mitochondrial function to match nutrient supply. The more NAD there is in cells, the more Sirt genes do beneficial things. There are studies that show the SIRT1 protein induces the formation of new mitochondria. NAD can also activate another sirtuin, SIRT3, which is thought to keep mitochondria running smoothly. It is now clear that sirtuins are involved in the regulation of many fundamental biological processes throughout the body. Sirtuins have evolved to respond to the availability of NAD which is now considered an essential element of cellular metabolism and DNA damage repair. The Sirtuin proteins are related to many of the different aging pathways in the body. If we would have to pick one aging pathway as the most important we would say it is the Sirtuin pathway. In addition to maintaining the health and numbers of the mitochondria another essential role of the sirtuins is that they remove acetyl groups from other proteins. The acetyl group is found at the end of various proteins. This process of removal of this group is called deacetylation. When the acetyl group is removed, it may allow the protein to become activated and have an effect on numerous other pathways in the body. This process is called transcription. What is really happening is that certain genes are being turned back on. As we age these genes become “turned off” while the Sirtuins seem to have an effect on many different pathways of aging by turning back on certain genes. EPIGENETICS This is one of the newest concepts in aging or shall we say anti-aging. This is an exciting new field called Epigenetics. Epigenetics, as a simplified definition, is the study of biological mechanisms that will switch genes on and off. Dr. Sinclair and his research lab at Harvard are convinced that changes in gene expression in response to DNA damage and lack of Sirtuin input may be a chief cause of aging. He is a strong believer in restoring the health of the mitochondria. Recently (Oct 2019), researchers at Yale Univ. proposed that a metabolic dysfunction of the mitochondria as responsible for Alzheimer’s disease. There are now two competing hypotheses are currently proposed to explain the cause of Alzheimer’s: the first is focused on the accumulation of amyloid-beta protein in the brain as the primary cause; while a second and more recent hypothesis proposes that metabolic dysfunction, specifically a dysfunction of the mitochondria, is responsible. Furthermore, is felt that epigenetics is at play here. Another aspect of NAD is its responsibility for DNA repair. In regard to DNA repair, NAD is broken down into two component parts, one of which (nicotinamide) gets recycled, while the other (ADP-ribose) meets up with a protein to repair the cell’s DNA. This research formed the foundation of the field of PARPs, or poly (ADP-ribose) polymerases, a group of proteins that rely on NAD to function and regulate DNA maintenance, among other biological functions. Remember as we age the amount of DNA damage is ever increasing. DNA damage will cause more genes to turn off or on. Without NAD, the DNA damage continues to accumulate causing more and more problems such as cancers and other degenerative conditions. We should also keep in mind that PARPs are very large consumers of NAD. This is one of the reasons why we become deficient in NAD. Thus, we can see that NAD has two huge effects. The first is that it has a direct effect on the mitochondria, the cell’s battery. It supplies power to the cell which in this case is called ATP. Secondly, NAD is an essential Co-enzyme in a wide variety of biological processes. The bottom line is if we are deficient in the enzymes or the ATP many bad things begin happening. Unfortunately, our NAD levels significantly decline as we age. The next question to ask is how to supply NAD to the body? We are not able to give the body NAD directly. Typically, the most common form of an NAD supplement given to the body is Nicotinamide Riboside which is often called NR for short. Nicotinamide Riboside is a form of Vitamin B. There are other compounds that can contribute to the formation of NAD. NR is one of a few variations of B3; others include Nicotinic acid (also called niacin) and Nicotinamide Mononucleotide. These other forms of NAD precursors are not as efficient in producing NAD as NR is. However, we must realize that the best way to increase NAD levels is by providing it to the body directly by either by an intravenous route or by some other method which gets it directly into the blood stream. We have found that the intravenous route is the quickest and most efficient method of increasing the cellular NAD levels. One must realize that when given intravenously NAD must be given slowly to avoid some NAD side effects. These side effects may be a nuisance but they are not serious. We are now looking into other methods of increasing NAD levels. One intriguing method involves injecting large dosages of NAD into the scalp with various micro-needling injection techniques. This is a very promising technique that will dramatically cut down the time required to deliver a dose of NAD to the body. We suspect this may be the method of the future in delivering NAD. This is a technique we are actively assessing. Depending upon the condition being treated, the intravenous dose of NAD will vary. The more serious problems will require higher and more frequent doses. Once adequate levels are reached it is imperative to continue dosing on oral supplementation of NAD. Not wanting to rest on the status quo we have looked into other methods that will increase NAD cell delivery. One aspect that is intimately tied in with NAD is a gene called the NQO1 gene. Another name for this gene is the “longevity gene”. NQO1 regulates aging by altering the NAD/NADH ratio in cells. NQO1 does this by oxidizing NADH to NAD. In other words, the NADH gives up an electron and gets converted to NAD. NQO1 is the gene that codes for the protein “NADH-quinone oxidoreductase 1”. This enzyme will deliver the electron to the NAD. Not only is the NAD content in the nucleus important for delaying or preventing aging, the redox ratio of NAD/NADH is also very important for delaying delaying/preventing aging independently of the total NAD found in the cell. So now we see there are intricacies in the NAD science. It is not just the NAD content in the cells but the ratios of NAD/NADH. There is very strong evidence that the NAD/NADH ratio is extremely important for anti-aging purposes. When considering the NQO1 gene we are just discovering its importance. It has many far-reaching effects. It appears that the NQO1-dependent pathway is the most important pathway for regulating P-53 levels within the cell. The P-53 gene is also called the tumor suppressor gene. Its job is to patrol the cells and analyze them. It will help repair DNA damage or if the cell is damaged badly it will cause the cell to go on to death. It acts as a guardian of the genome. As its name suggests, P-53 is called the tumor suppressor gene. This gene is very important in cancer suppression. Obviously if we have a compound that will increase the effectiveness of NQO1 that is very important on a few different levels. We have a supplement that does this. This compound is Beta-lapachone, a compound found in the bark of the South American Lapacho tree. The name for this is Pau D'Arco. We provide this medication to our patients to enhance the NAD/NADH ratio and as a side effect stimulate the NQO-1 gene. We typically encourage the use of this medication for 15 days on than stop for 5 days than continue for another 15 days and repeat the cycle until the bottle is finished. A patient will take one tablet twice a day. Another recommendation we have with NAD supplementation is the use of Quercetin. Quercetin is a plant pigment (flavonoid) supplement. It is found in many plants and foods, such as red wine, onions, green tea, apples, berries, Ginkgo biloba, St. John's wort, American elder, and others. In this case we are using Quercetin for a few different reasons. First it seems to have an effect on certain pathways (Nrf2) that ultimately seem to stimulate the longevity gene NQO1. Remember NQO1 effects the NAD/NADH ratio in a positive manner so typically we are going to increase the overall effects of NAD. As a side note the Nrf2 pathway is a pathway that turns on your own body’s mechanism to remediation of oxidative stress. One can consider it as the body’s thermostat for oxidative stress. Getting back to Quercetin, it is also used as what we call a Senolytic agent which is something that kills a certain type of cell called a Senescent cell. This brings us to an important concept in NAD therapy. Unfortunately, this is a concept the most clinics utilizing NAD therapy do not address. Senescent cells start as healthy cells that experience stress which causes them to enter a state known as cellular senescence. In this state, cells stop dividing and profoundly alter their metabolism, appearance, and interactions with their environment. The sub cellular damage itself does not directly cause the visible signs of aging, but rather, as the damage accumulates and reaches a critical mass, cells cease to proliferate and acquire the deleterious “senescence-associated secretory phenotype” (fancy way of saying the cells have changed character and altered the compounds they produce) which then leads to the consequences of tissue breakdown to create an aged cell. Thus, senescence is a precondition for tissue aging. One can think of Senescent cells as zombies which ultimately infect normal cells. As we age these cells become more and more numerous. It is now felt that eliminating them can increase our overall health. These cells are thought to be responsible for a host of diseases of aging from Osteoporosis to cancer. The following diagram explains the ramifications of cell senescence. What we need to avoid the NAD treatments having a positive effect on the Senescent cells. We do not want to make the Senescent cells more vigorous and subsequently cause many bad things. Instead we want to try to eliminate many of these cells. We have addressed this for some time. The Quercetin is a potent senolytic agent (a compound which kills the senescent cells) while at the same time boosting NAD levels. To take the senolytic agents to the next level we sometimes will add a course of Dasatinib with the Quercetin. This same technique has been utilized by various University studies in their protocols concerning senescent cells. We take Senescent cells very seriously knowing the damage they are capable of doing. These cells are significant contributors toward aging. It is now clear that NAD decline is one of the fundamental molecular events that regulate the process of aging. NAD in the body is in a very delicate balance between consuming enzymes which are fixing DNA damage, between helping mitochondria produce ATP, and allowing the Sirtuins to do their work on various aging pathways in the body while having a profound effect on the Epigenetics of genes. Any deviation from this delicate balance side can cause significant derailment of the system. The good news is that one cannot overdose on NAD. We now have increasing bodies of evidence supporting that interventions using intravenous NAD followed by oral intermediates, such as NMN and NR, can bolster the system by restoring the available NAD and mitigate physiological decline associated with aging. We are now at the point where we can effectively raise NAD levels for the prevention and treatment of aging and aging-related diseases. Remember, we are always pushing the envelope on treatments. -Dr. P

Many people know me from my blogs that I write on the website. Unlike most people, I do not use ghost writers. I write my own material. There is another group of people who know me from my comments on LinkedIn. The above represents one of the articles I recently commented upon on LinkedIn. What I find interesting is that the above article gives a glimpse into my journey in Regenerative Medicine. As I stated, many years ago when I became involved in Regenerative Medicine, it was the dogma that Mesenchymal Stem Cells were the only cells that accomplished repair. Well, that certainly has changed, as can be seen by the 1900+ hits this short article has gotten. We now know that a symphony of cells accomplish repair. This article reminded me of my journey into the field of Regenerative Medicine. The groundwork for my journey began as a typical Orthopedic surgeon. I was seeing patients in the office, and at the same time having a very busy operative practice. My week would consist of performing total joint replacements, performing arthroscopies, and doing spinal laminectomies. Of course, my occasional weekend was involved in repairing hip fractures and a variety of other fractures. In those days, there was not the specialization in Orthopedics as there is today. I did many of these surgeries, but at the same time I thought that these were rather barbaric operations. I was basically doing carpentry on patients. When I finished my residency, the field of Arthroscopic Surgery was just getting started. I remember some of the more “seasoned” orthopedic surgeons that I met in private practice said to me that arthroscopy was just a fad that would die out in a few years. Initially, they looked at me in scorn thinking I was doing some type of quackery surgery. Well, I guess they were wrong! I became very proficient with the arthroscope, and did many surgeries, as did the rest of the Orthopedic community. Although the initial results in arthroscopic surgery were excellent, later on in my career I realized that these surgeries were actually causing patients to develop osteoarthritis at a young age, and this concept is now supported in the literature. I started to become disillusioned with this treatment protocol, but at the time did not know what could be a better option. I would go to conferences to learn the latest techniques which, when all was said-and-done, was not much different from older techniques. One thing I was always drawn to was the cutting-edge techniques. I was at one time involved with injecting chymopapin into herniated discs. Chymopapin is the enzyme found in meat tenderizers. In this case, it would disolve the herniated disc. The results we obtained were very good. After this technique, I moved on to laser discectomies. Both of these methods gave excellent success in the right patient. I would call these episodes my springboard for regenerative medicine. Total joint replacements were my formal indoctrination to the world of Regenerative Medicine. I was doing joint replacements, and I went to a conference where they discussed a “new technique” called PRP or Platelet Rich Plasma. They said that this helps the joint replacement patient heal quicker and, in general, have less pain. I started using this “new technique” with excellent success. I started studying more about PRP, and realized that this is the way nature heals itself. This was my “A-ha!” moment. I realized that the PRP technique could be used in many other applications besides total joints. My second “A-ha!” moment was that perhaps this might eventually replace the joint replacement itself. I was now at the fork in the road. I could continue doing everyday orthopedics, or I could get more involved in the path that led to the use of biologics for orthopedic conditions. I went down this path when few people even knew what a PRP was. Those that knew about a PRP typically did not know much about bone marrow aspirate or adipose tissue. Bone marrow and adipose were my next targets to learn and study. They fell into place quickly. This time period reminded me of the time when I first went into private practice, and began doing arthroscopic surgery. The more established orthopedists said this was a fad and recommended against it. Well, fast-forward twenty years and the same comments were being made by the Orthopedic community about PRP. They said that PRP and Regenerative medicine was “Hocus Pocus Surgery.” They said that it was a fad with no scientific basis, and the talk behind my back was causing my ears to burn. I stood steadfast in my convictions and I am so happy I did. Slowly, more acceptance crept into the field. I was eventually lecturing all over the world, and continue to do so. As a matter of fact, I leave tonight for a quick teaching trip to Brazil. I will be there for about a day and a half and then return to the USA. In that time, I will talk about the basic science of stem cells and regenerative medicine. This is interesting, in that, most clinicians try to disregard basic science and usually are not involved in teaching. Well, low and behold, I now find myself teaching of all things about the basic science of stem cells and Regenerative Medicine. As a matter of fact, I have taught on all six continents. If someone would have told me this twenty years ago, I would have bet the farm against it. It is interesting how life takes some unexpected turns. I realized that in order to become proficient in anything, one must learn to master the basics. Every day, I try to learn more basic science in the field of Regenerative Medicine. It reminds me of one of my slides in my talks, “the more you know the more you don’t know.” That is actually a profound statement because of its simplicity. Using this knowledge of basic science has allowed me to expand the horizons and successes of our clinics. We are involved in cutting-edge aspects of anti-aging medicine that down the road will become building blocks of mainstream medicine. I have learned that the way stem cells age is how we age. These aging pathways include eliminating senescent zombie cells and stimulating gene pathways to improve the health of our mitochondria. I have realized that Anti-Aging, Stem cells and Regenerative Medicine have a strong bond that ties all of them together. It has been an exciting journey that I look forward to continuing. Regards, - Dr. P