Anti-Aging Therapeutics Volume XVII

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A4M American Academy. Anti-Aging Therapeutics Volume XVII

Chapter 1. President’s Message: A4M at the Helm of $295 Billion Marketplace – Achievements and Future Horizons. Ronald Klatz, M.D., D.O

INTRODUCTION

OVERVIEW

ACCOMPLISHMENTS

ADOPTION

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 2. Energy Medicine Going Mainstream. Silvia Binder, ND, Ph.D

“If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.”

CASE HISTORIES. RL, a 5-Year-Old Male Diagnosed with Thrombosis on the Heart Valve

Myasthenia Gravis

Lymphedema

CONCLUDING REMARKS

Chapter 3. Managing Terrorism or Accidental Nuclear Errors, Preparing for Iodine-131 Emergencies: A Comprehensive Review. Eric R. Braverman,Kenneth Blum, Bernard Loeffke, Robert Baker, Florian Kreuk, Samantha Peiling Yang, James R. Hurley

ABSTRACT

INTRODUCTION

REVIEW AND RECOMMENDATIONS

KI Agency Recommendations

Potassium Iodide Prophylaxis Review. Potassium Iodide Prophylactic Historical Success

Potassium Iodide Prophylaxis – Lowest Effective Prophylactic Dose

Iodine-131 Biological and Physical Analysis

Shelf-Life of Potassium Iodide

Potential Use of Food for Iodine Prophylaxis

Iodine Deficiency and Dietary Iodine

Side Effects of KI Prophylaxis

KI Distribution Review. KI Pre-Distribution and Radiological Plumes

Meteorological Conditions and Plume Size

Iodine-131 Dispersal Methods

Iodine-131 Historical Radiological Exposures

Iodine-131 Physiology, Health, and Therapeutics. Iodine-131 Routes to Exposure

Iodine-131 Field Detection Methods

Radiation Phobias and Psychological Effects

Federal and State Emergency Preparedness Plans

Iodine-131 Industrial Usage

Health Effects and Medical/Therapeutic Use

Iodine-131 Medical Dosage and Public Legal Limit

Iodine-131 Exposure Side Effects and Condition Co-Morbidities

Post Iodine-131 Exposure Patient Precautions

Future Perspectives. Iodine-131 Potential in a Dirty Bomb

Worldwide Iodine Deficiency

Our Recommendations Based on This Review. Potassium Iodide Prophylaxis is Effective and Necessary

The Effectiveness of KI Prophylaxis is Lost if Administration is Delayed

Extension of the Thyroid Disease Risk Area to Exceed 300-Miles

Reduce Costs of Stable Iodide Prophylaxis to Extended Thyroid Disease Risk Area

Give Information and Clear Instructions

Facilitate Good Nutrition in Populations with Iodine Deficiency

Avoidance of Exposure Is No Longer an Adequate Response to a Nuclear Event

Plan for Swift Access to Radiation Isotope Identification Device (RIID)

CONCLUDING REMARKS

REFERENCES

APPENDIXES

ACKNOWLEDGMENTS

AUTHOR CONTRIBUTIONS

ABOUT THE AUTHOR

Chapter 4. Nitric Oxide, Menopause & Female Sexual Arousal Disorder. Nathan S. Bryan, Ph.D

ABSTRACT

INTRODUCTION

NITRIC OXIDE AND ERECTIONS

NO INSUFFICIENCY, SEXUAL DYSFUNCTION AND CARDIOVASCULAR DISEASE

NATURAL REMEDIES FOR SEXUAL DYSFUNCTION

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 5. Detoxification Lifestyle with Case Study. John Cline, M.D., BSc, IFMCP

ABSTRACT

INTRODUCTION

DETOXIFICATION STRATEGIES

Decrease Toxin Exposure

Optimize Biotransformation

Increase Mobilization of Stored Toxicants

Decrease Redistribution and Increase Excretion

Nutrition and Hydration

Exercise and Movement

Stress and Resilience: Relationships and Networks

Sleep and Relaxation

CASE STUDY

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 6. Introduction to Regenerative Medicine and Clinical Applications of Cellular Therapies. Kristin Comella, MS

ABSTRACT

STEM CELL BASICS

Embryonic Stem Cells

Induced Pluripotent Stem Cells

Adult Stem Cells

Bone Marrow Stem Cells

Adipose Derived Stem Cells

Muscle Derived Stem Cells

Placenta/Cord Blood Stem Cells

PLATELET RICH PLASMA

REGULATORY ENVIRONMENT

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 7. Tame the Flames of PCOS: An Integrative Approach to a World-Wide Epidemic. Felice L. Gersh, M.D

ABSTRACT

INTRODUCTION. An Overview of a Complex Problem

THE ETIOLOGY OF POLYCYSTIC OVARY SYNDROME. Endocrine Disruptors Alter Hormone Receptor Functioning and Production

The Beginning of Severe Symptoms: The Onset of Puberty

On Fire: PCOS is a State of Chronic Inflammation

Adiponectin

The Role of Mononuclear Cells and Chronic Inflammation in PCOS

The Role of the Gut

DIAGNOSIS AND TREATMENT OF POLYCYSTIC OVARY SYNDROME

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 8. Mesenchymal Stem Cells for the Treatment of Arthritis. Rafael Gonzalez, Ph.D

ABSTRACT

INTRODUCTION

USING MESENCHYMAL STEM CELLS TO TREAT ARTHRITIS

MSCs and the Treatment of Osteoarthritis: Case Studies

Allogenic Stem Cell Transplants

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 9. Everything You Wanted to Know About Cannabidiol but Were Afraid to Ask. John H. Hicks, M.D. ABSTRACT

INTRODUCTION

MECHANISM & THERAPEUTIC POTENTIAL

RESEARCH

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 10. Nutritional & Medical Applications for Cannabidiol: Hemp Health Benefits without THC. Joseph Maroon, M.D., FACS; Jeff Bost PAC; Christina Mathyssek, Ph.D

ABSTRACT

INTRODUCTION

Hemp is Not Marijuana

Modern Medical Marijuana

NUTRITIONAL AND MEDICAL APPLICATIONS FOR CANNABIDIOL. What is Cannabidiol?

Actions of Cannabidiol

Selective CB1 and CB2 Actions of THC and Cannabidiol

Medical Therapeutics of Cannabidiol

Summary: Actions of CBD

Anti-inflammatory15

Analgesic Effects17,18

Anti-nausea, Anti-emetic & Gastrointestinal Benefits11,20-22

Anxiolytic13,23

Anti-epileptic14,24-26

Neuroprotective10,32

Anti-cancer37

Dosing and Safety

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHORS

Chapter 11. Beyond Lipids: Advanced Inflammatory & Cardiometabolic Biomarkers in Clinical Practice. Robert J. Megna, D.O., MS

INTRODUCTION

RISK FACTOR ANALYSIS

Inflammatory Cytokines

HS-CRP

MYELOPEROXIDASE

LP-PLA2

FIBRINOGEN

F2 ISOPROSTANES

ENDOTHELIN

II-DEHYRO THROMBOXANE B2

CYP2C19

CYP2C9 AND VKORC1

FACTOR V LEIDEN AND PROTHROMBIN G20210A

HOMOCYSTEINE

MTHFR

APO E

CARDIAC TROPONIN I

NT-PROBNP

GALECTIN 3

CYSTATIN C

ADIPONECTIN

LEPTIN

REFERENCES

ABOUT THE AUTHOR

Chapter 12. New Comprehensive Protocols for Addressing Today’s Deadly Triad: Diabetes, Alzheimer's, and Heart Disease. Chris Meletis, ND. ABSTRACT

INTRODUCTION

CAUSES OF CHRONIC INFLAMMATION. Diabetes – the Link between Diabetes and Alzheimer’s

The Importance of Optimal Cortisol Levels

PROTOCOLS FOR REDUCING CHRONIC INFLAMMATION. Harnessing PPAR Regulation with Select Nutraceuticals

Berberine

Diet/Nutrient Support

Stephania Tetrandra

Boswellia

Curcumin

Niacin

Vitamin B12

Green Tea

Magnesium

Coenzyme Q10

Nitric Oxide

Sleep Promotion

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 13. The Hormone Secret: Discover the Missing Link to a Better Body, Brain and Life. Tami Meraglia, M.D. ABSTRACT

INTRODUCTION

TESTOSTERONE: THE MISSING LINK

Testosterone – More than Just Libido

Bone

The Brain

Muscle

Mood

Energy Levels

The Heart

Insulin Resistance

Red Blood Cell Production

Cancer Risk

RESTORING TESTOSTERONE TO OPTIMAL LEVELS

How to Increase Testosterone Without a Prescription

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 14. Clinical Approaches to Obesity: Western and Eastern Medicine Perspectives. Oxana Nikolenko, M.D

INTRODUCTION

CLINICAL OVERVIEW

MEDICAL COMPLICATIONS OF OBESITY

PRINCIPLES OF AN ORIENTAL MEDICINE PERSPECTIVE

CASE STUDIES. Irene L

Michael C

Oksana B

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 15. Platelet Rich Plasma and Stem Cell Injections. Joseph Purita M.D., FACS, FAAOS, FAAMP

ABSTRACT. The aim of this paper is to consider the science behind platelet rich plasma (PRP) and stem cell injections. Treatment protocols and contraindications are also considered. Keywords: PRP, BMAC, SVF, stem cells, plasticity, biologics. INTRODUCTION. This paper offers an introduction to PRP and stem cell injections. A major gap has existed for the treatment options between conservative treatments and surgery. This gap is now filled by stem cell and PRP injections. The goal of this presentation is to enable the physician to perform stem cell injections and PRP injections in an office setting in an efficient, safe, and economical manner. The use of stem cells, PRP, and scaffolding material such as fat grafts, form what can be called the healing trinity – all of these aspects work together to achieve healing in the musculoskeletal system. PLATELET-RICH PLASMA. At one time, it was thought that platelets were basically responsible for clotting the blood and that was all. Nothing could be further from the truth. When the platelets are concentrated the growth factors are also concentrated. These growth factors are what cause things to heal. They recruit stem cells and have direct effects on many different types of tissue. PRP contains a number of different kinds of cells including: •Platelets; •Neutrophils, which represent 40% to 75% of the circulating leukocytes; •Monocyte/macrophages, which represent 2% to 10% of the circulating leukocytes; •Fibroblasts, which produce collagen, reticular fibers, glycosaminoglycans, and glycoproteins – these compounds are very important in the production of tendons and articular cartilage; •Endothelial cells – these regulate permeability barriers, blood flow and vascular reactivity, act as vasodilators and constrictors, and regulate inflammation and immunity; •Keratinocytes, which are stratified squamous epithelial cells. Their primary function is to act as a barrier •Research suggests that PRP may contain primitive very small embryonic-like stem cells (VSELs).1. Are all Platelet Rich Plasma Preparations the Same?

Platelets are a Rich Source of Growth Factors. The real power of the platelets rests in the growth factors which they contain. Platelets contain 2 unique types of granules. These are the alpha and the dense granules. The alpha granules contain a variety of hemostatic proteins (coagulation proteins), as well as growth factors, cytokines, chemokines (pro-inflammatory activation-inducible cytokines), and other proteins such as adhesion proteins. Of primary interest to the clinician are the three adhesion molecules and seven growth factors present in the alpha granule. The dense granules contain factors that promote platelet aggregation (ADP, calcium, serotonin). For our purposes the alpha granules are the most important granules. The growth factors present in the alpha granules stimulate mesenchymal stem cells (MSCs) to help produce endothelial, fibroblastic, and osteoblastic components. They also promote the growth and differentiation of chondrocytes, fibroblasts, and osteoblasts. Perhaps the most important thing that the platelet growth factors accomplish is the establishment of a blood supply. Without a blood supply the stem cells themselves will by and large be doomed due to their inability to obtain the necessary growth factors they require. A good analogy is to think of the stem cells as an army that is advancing and the blood supply as its supply lines. In most cases, if the army advances beyond its supply lines it leads to defeat. Understanding the complex interactions involved with the various types of cytokines or growth factors can be difficult because of the confusing nomenclature. Specifically, some cytokines are named for their cell of origin (e.g. platelet derived growth factor = PDGF) whereas others are named for their target cells (e.g. epidermal growth factor = EGF). In addition, some cytokines are named for their first purported action (e.g. transforming growth factor beta = TGF-β). Finally, the actions of the cytokine may be complex in number and unable to be described by a single name. The mechanism of action of the cytokines may be either through endocrine (secreted by one population of cells and having distant effects on another), autocrine (secreted by cells which are then themselves modulated by the factor), or paracrine (secreted by the cells and affecting neighboring cell populations) activity. There are now some schools of thought which believe that stem cells function in much the same way (autocrine, paracrine, or endocrine) as small biochemical factories producing certain biofactors that affect cells nearby, distant cells, and the stem cells themselves. Essentially, growth factors released by activated platelets (Fig. 2) play an important role in the proliferation and differentiation of stem cells

Platelet Rich Plasma in the Office Setting. A PRP graft is made in the office setting with the use of one of several available tabletop centrifugation machines. For the clinician first starting out to do PRP injections, it is best to use one of several companies that produce tabletop machines. Basically, each machine has a separate disposable unit that concentrates platelets in a small amount of plasma, typically 10 ml. The use of tabletop models offers a safe, reliable, and reproducible method of obtaining PRP. They also insure a sterile environment for the PRP. Some companies may loan a centrifuge on the assumption that you will use their separate disposable self-contained units that concentrate the platelets in a small amount of plasma. These units have a one-time use and cost anywhere from $150 to $250. Once injected into the tissue PRP will begin initially with the inflammatory phase, which includes activation of the platelets, release of growth factors, and a myriad of other reactions. The next phase is the proliferative phase. In this phase various types of cells begin to proliferate and subsequently go onto the next phase, which is the remodeling phase. The modeling phase includes tissue repair that starts with the production and breakdown of collagen products. Typically this phase can last for over a year. Sample Injection Therapy Protocol. When performing PRP injections, the amount of blood utilized depends somewhat on the problem that is to be tackled. For instance, when treating an elbow, foot, or hand, approximately 22 ml of whole blood is utilized. For larger applications, such as a shoulder, knee, or hip joint, approximately 60 ml of whole blood will be utilized. Using 22 ml of whole blood typically produces 3 ml of PRP, while 60 ml of whole blood will produce anywhere from 7 to 10 ml of PRP. Once the blood is obtained from the patient it is then necessary to centrifuge the blood to separate the platelets from the other remaining blood products. What we obtain from the disposable units are platelets and leukocytes. The platelets can be found directly above the leukocytes and this is called a buffy coat of centrifuge blood. Since the buffy coat contains elevated levels of leukocytes, the PRP is essentially bactericidal. The only organisms that PRP does not seem to have bactericidal effects on include Klebsiella pneumoniae, Enterococcus and Pseudomonas.3. It is not currently known what the actual optimal concentration of PRP-enhanced growth factors should be. There seems to be a perception among various researchers that a 4 to 6-fold increase in the number of platelets may have a bit more of an anti-inflammatory effect rather than inflammatory. It seems that higher concentrations of platelets seem to push the scale more towards an inflammatory nature, although this may be related to the fact that there may be more white blood cells in the concentrate. However, there are ways of ameliorating any inflammatory effects and these will be discussed. The use of thrombin as a way of producing a gel matrix and releasing growth factors is mentioned many times in the literature. At this point, it is important to note that the use of thrombin is not necessary and may be contraindicated. The platelets will become activated when they come in contact with the tissue. Many studies suggest that without thrombin there may be a slower release of growth factors which may prove beneficial. Once the graft is prepared it is then time to place the PRP graft in a proper area. Injections should be given via whatever method the physician feels most comfortable with. Ultrasound guidance or other means of guidance, such as radiographic, palpation, or clinical examination to locate the area of concern, can all be used. However, the most important diagnostic aide is “road testing” the patient. By road testing, we mean giving the patient lidocaine anesthetic in the area of pathology. If you are then able to eliminate the patient’s pain in this area than this is the area we want to inject the PRP into, as it is this area that obviously has the pathology that is causing the patient his symptomatology. We are all too well aware that various scans can show many different findings and only some of these findings are clinically significant. If you road test the patient and eliminate his pain, this is where you put your graft. By using this method you will have very little problems and will have high a success rate. Firstly, Betadine should be used to disinfect the skin and then lidocaine should be used to anesthetize the area. It is important to avoid the use of Marcaine® (bupivacaine) as some studies suggest that Marcaine® could be toxic to the stem cells, furthermore it is known that Marcaine® can be toxic to chondrocytes. The technique for injecting the area of pathology depends on the clinician’s sense of clinical acumen. The actual injection technique depends upon the site involved. For instance, for a joint it is only necessary to place the PRP anywhere into the joint as it will spread to the involved areas on its own. Thus, it is not necessary to use any real guidance to place the PRP for a meniscus tear since the cells will travel throughout the knee. However, for a tendon it is best to inject the PRP into the tendon sheath and then the tendon itself in a peppering fashion. A 23 gauge needle is acceptable to use for this. If we have a musculotendinous junction it is actually a good idea to go many times down to the bone itself. Numerous common musculoskeletal conditions are treated with PRP, these include: •Disorders of the shoulder including bursitis and rotator cuff tears; •Tendonitis of a variety of tendons including tennis elbow, Achilles tendonitis, and heel spur syndrome; •Muscle tears, sprains, trigger points; •Meniscus tears of the knee; •Mild-to-moderate degenerative arthritis of various joints; •Disorders of the spine including facet arthropathies and disk problems. As with any technique, certain patients will not be candidates for PRP injections. Various blood diseases would very much negate the use of PRP injections in patients. The consistent use of nonsteroidal anti-inflammatories (NSAIDs) is somewhat more controversial. A few years ago it was thought to be gospel that patients have to stop taking NSAIDs when undergoing PRP injections. However, after further study and personal communications with Drs. Sherwin Kevy and May Jacobson. Of the CBR Institute for Biomedical Research at Harvard University, I feel that the use of NSAIDs do not seem to make a difference either way. Some theorize that they would perhaps interfere with the release of growth factors, though experience shows that NSAIDS do not appear to have any significant effect on the release and function of growth factors. At present, we restrict the use of NSAIDs for about 2-days – one day before and one day after the PRP injection. After that they are not a problem. Cortisone injections at the site of treatment or systemic use of cortisone are probably somewhat detrimental to the PRP injection. Active cancers should act as a contraindication for PRP use. Infections especially Pseudomonas, Klebsiella, and Enterococcus should also negate the use of PRP. In summary, PRP injections offer the clinician a new and exciting method of treating many injuries which, until this point, were the realm of the orthopedic surgeon in the operating room. These injections will respond very well for numerous musculoskeletal conditions. Note: It is vital to tell the patient that these injections do take time. The analogy to use with a patient is that PRP injections are very much like renovating a house – it takes time. Note: Results of a study by Wasterlain4 showed that PRP injection resulted in a significant rise in serum (i.e. systemic) insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels – all of which are banned by the World Anti-Doping Agency (WADA). The WADA banned PRP in 2010, however in 2011 this ban was lifted as there was little evidence that PRP had a systemic effect. The results of this study suggest that the WADA may rethink their stance on PRP. Thus, it is vital to be very cautious when considering treatment with PRP injections in competitive athletes. Autologous Protease Inhibitor Concentrate – The Next Platelet Rich Plasma? In the very near future it is likely that autologous protease inhibitor concentrate (APIC) will be in frequent use in esthetics, orthopedics, and wound care. APIC is similar (but not the same) as Regenokine. APIC is also known as A2M, as its major ingredient is α-2-Macroglobulin (A2M), a broad spectrum protease inhibitor. A2M is found in high concentration in the blood (up to 6 mg/ml) and is a potent inhibitor of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines. I have been using A2M for around a year, and am very happy with it. If a patient is not responding well to PRP I will try A2M, and more often than not, the results are good. Many people assume that A2M will be prohibitively expensive, that is not the case. At present it costs approximately $500 a treatment, and so is more expensive than PRP. For this reason I only tend to use it in cases where PRP is not working. STEM CELLS. Stem cells are generally defined as undifferentiated cells that are capable of self-renewal through replication. These are cells that differentiate into specific cell lineages. Adult stem cells are necessary to maintain tissue and organ mass during cellular turnover. There are a number of terms that one needs to know when talking about stem cells. These terms are: •Multipotent: Multipotent stem cells are decedents of pluripotent stem cells and antecedents of specialized cells in particular tissues. Multipotent stem cells yield a more restricted subset of cell lineages; •Progenitor cells: These are unipotent stem cells that can produce only one cell type. A progenitor cell cannot renew itself; •Stromal cells: A mixed cell population that generate bone, cartilage, fat, and fibrous connective tissue; •Plasticity: The ability of stem cells from one adult tissue to differentiate into cell types of another tissue; There are many different types of stem cells: 1.Embryonic stem cells (ESCs); 2.Adult mesenchymal stem cells (MSCs); 3.Hematopoietic stem cells (HSCs); 4.Induced pluripotential stem cells (iPSCs); 5.Various other more specific type of stem cells; 6.Very small embryonic stem cells (VSELs) possibly called blastomere-like stem cell; 7.Muse cells derived from adipose tissue; 8.Somatic nuclear transfer cells (SNTC); For our purposes we will concentrate on just 4 types of stem cells – ESCs, adult MSCs, HSCs, and iPSs). Each has its strong and weak points. Embryonic Stem Cells. ESCs are by far the most controversial type of stem cell. The US government has lifted some of its bans on ESCs, but the FDA still significantly restricts their use in people. ESCs seem to present the most potential for correcting and curing certain conditions due to their plasticity or ability to morph into many cell types. In addition to certain ethical issues, ESCs pose a number of scientific reasons why at present they will not be used in mainstream treatment: •Patients will inherit any potential disease that the embryo may have; •There is a significant potential that the cells can grow unchecked and essentially act as a tumor if injected into a patient; •There are certain immunogenic factors that must be dealt with: Will the body attack the stem cells as being foreign? Will the patient develop graft versus host disease? Thus, the patient may be required to take drugs to ward of cell rejection. Hematopoietic Stem Cells. HSCs are the cells that form blood products, such as white and red blood cells, and are often referred to as CD-34 stem cells. HSCs are the drivers of tissue regeneration not MSCs. These non-adherent cells drive tissue regeneration. HSCs have been shown to upregulate cytokine release, which stimulates additional HSC and MSCs from intact bone to travel to the site of damage.5 HSCs have also been shown to upregulate production of VEGF and other cytokines that support angiogenesis and vasculogenesis,6 and directly forming bone by differentiating into MSC and then osteoblasts.7 Basically, the primary engine of new bone and cartilage formation in vivo is thought to be the recruitment and differentiation of cells classically defined as hematopoietic in origin. Indeed, several lines of evidence demonstrate that endothelial cells, vascular smooth muscle cells, and pericytes are capable of differentiating into osteoblasts. In a study published in Stem Cells, Grcevic et al concluded: “Our data indicate that the majority of the callus cells, including chondrocytes and osteoblasts, are derived from SMA9-expressing cells. Interestingly, the expansion of the SMA9 cells occurred both in periosteum and within bone marrow and resulted into SMA9+ cells with mature bone cell phenotypes contributing to the fracture-healing process. We were able to identify mesenchymal progenitor cells that actively participate in the fracture healing process by differentiation into mature chondrocytes and osteoblasts.”8. Figure 6 illustrates the principle of plasticity. Stem cells help to establish a blood supply where there previously had not been one. The principle of establish hing a blood supply is very important in stem cell science. Due to their plasticity, HSCs have the ability to turn into other types of stem cells. For our purposes they would turn into MSCs. With HSCs it is best to stimulate their production and let the body deliver them to the involved areas by other methods (PRP and other stem cell injections). HSCs can be obtained by apheresis. However, the equipment needed for apheresis is very expensive and the cost of each procedure is at least $1000, which makes this an impractical procedure for an office-based practice. Furthermore, HSCs are not the best cells for our purposes

Induced Pluripotential Stem Cells. iPS cells are produced from manipulating adult cells into becoming stem cells by enzymatic or viral means. This process works by inducing a “forced” expression of specific genes. iPS cells seem to act in a similar manner to natural pluripotent stem cells. The use of viruses in these cells poses a significant risk since it may trigger oncogenes, however cells treated with certain proteins may not pose this risk. The larger problem with iPS cells is that their telomeres are shortened. Remember, these are adult cells whose telomeres are old and shortened. The best analogy one can use concerns Dolly the cloned sheep. Dolly died of old age at a young age due to telomere shortening. Basically, Dolly's DNA was old. Telomere shortening is probably going to become an important aspect of stem cell science. As can be seen in Figure 7, there is a distinct difference between the telomere length of an ESC and an adult stem cell. Although it has not been proven it appears that telomere length may have a direct effect on the plasticity of the stem cell. However, if we can find ways to increase telomere length, than we might be able to dramatically ramp up the efficiency of the stem cells to repair problems. Scientists are searching for compounds which stimulate the production of telomerase, the enzyme which places the lost DNA strand back on the chromosome. This research is headed by Dr. William Andrews of Sierra Labs, who is considered to be the pre-eminent telomere expert in the world. Telomeres are an important consideration not just for iPS cells but for all stem cells. The Nobel Prize in Medicine in 2012 was awarded for iPS cells

Mesenchymal Stem Cells. MSCs are the cells that repair muscle, bone, cartilage, or tendons. MSCs are commonly called adult stem cells. These stem cells are autologous (meaning that they come from the patient) and therefore there is no risk of genetic disease transmission. MSCs are the bodies’ repairmen; acting as construction managers and helping other cells repair and build new tissue. MSCs are the most important cells for our purpose. The good news is that since these cells are the patient’s own, there are minimal risks to the patient. cells for our purpose. MSCs were initially thought to be the most important type of stem cell because early technology was only capable of expanding and differentiating an MSC in vitro. This led to the incorrect conclusion that MSCs were the drivers of tissue regeneration, and that if we expanded enough of them and then transplanted them, we would have clinical success. MSCs can be isolated from almost every tissue in the human body. The central connecting aspect to explain this fact is that all of these tissues are vascularized and that every blood vessel in the body has mesenchymal cells in abluminal locations. These perivascular cells can be summarily called pericytes. MSCs are being used therapeutically because they home to sites of inflammation or tissue injury and they secrete massive levels of bioactive agents that are both immunomodulatory and trophic. A new realization is the possibility that all MSCs are perivascular cells or pericytes. These cells reside on every blood vessel in the body, and some of these cells become MSCs upon focal injury. By secreting factors which mute the immune system, the MSC-pericytes inhibit T-cell surveillance of the damaged tissue, while also releasing bioactive agents that establish a regenerative microenvironment. In 2010, Dr Arnold I Caplan, the researcher who named MSCs, wrote a letter to the editor of the journal Tissue Engineering Part A. In this letter Dr Caplan states: “I would suggest that MSCs are powerful site-regulated drug stores or dispensing sites that may serve as modulatory or curative agents for a variety of human maladies. Since the multipotency of MSCs is not the key aspect for their current therapeutic use, I herein propose a name change: medicinal signaling cells.”9. Although the differentiation of MSCs into bone and cartilage is still an important and potentially useful capability for tissue engineering applications, the immunomodulation capacity may have a more profound and immediate effect on joint chemistry and biology by muting or eliminating the chronic inflammation observed in osteoarthritis, rheumatoid arthritis, and severe focal injuries to skeletal tissues. There are some studies that suggest that culturing these cells outside the body can diminish their effectiveness. The reason for this might be that the telomeres are affected. Culturing these cells also misses a host of other cells and growth factors that are crucial in the overall repair process. For example, Vangsness presented results of a study of chondrogen (expanded MSCs) at the Annual Meeting of the American Academy of Orthopedic Surgeons 2012. Results showed that patients receiving a single low-dose injection of 50 million MSCs 1-week after meniscectomy reported significantly less pain 2-years later, however pain did not improve in those receiving the high-dose injection containing 100 million MSCs. Furthermore, at the 12-month mark, 23.5% of patients receiving the low-dose MSC injection had an increase in meniscal volume of more than 15% from baseline, indicating significant regeneration. But only 5.6% of the high-dose group met this endpoint

In addition, we are still unclear on the FDA’s stance on culturing MSCs, and there is the possibility that the FDA may consider cultured MSCs to be a drug. However, it appears to be within FDA guidelines to use these cells as long as they are put back into the same patient and they are minimally manipulated. MSCs are commonly found in the bone marrow, fat cells (especially the lower abdominal fat), circulating blood (not many), and in the joints (very few). In practical terms the stem cells available for an office setting include HSCs, MSCs obtained from bone marrow, and adipose stem cells. Adipose-Derived Stem Cells. Adipose stem cells are the richest source of MSCs in the body. The adipose stem cell has the ability to differentiate into chondrocytes, fibroblasts, and other musculoskeletal tissue. They seem to have very similar properties to bone marrow MSCs. The use of fat stem cells is a unique and promising approach and it holds key advantages over stem and regenerative cells from other sources. The abundance of stem cells in adipose tissue and the ability to easily collect large amounts of adipose tissue via liposuction eliminates the need for tissue culturing. Depending on the article one reads, there is anywhere between 500 and 2500-times the number of stem cells in adipose tissue as compared to bone marrow (Fig. 9)

Adipose tissue also contains a number of cytokines, which help regenerate tissue. The major cytokines are: •Hepatocyte growth factor (HGF), which has a major role in adult organ regeneration and wound healing; •VEGF, which stimulates the growth of new blood vessels without which repair is very difficult; •Placental growth factor (PGF), which encourages angiogenesis and vasculogenesis; •Transforming growth factor-beta (TGFβ), which controls proliferation, cellular differentiation, and other functions in most cells. The current methods of obtaining adipose stem cells are: the Cytori System, the Tissue Genesis system, the simple liposuction technique, and the simple liposuction technique combined with fat stem cell extraction. The Cytori and Tissue Genesis systems have very high costs for the office. The cost of these systems can be several hundred thousand dollars, and the kits that are used on a one-time basis cost upwards of $2500. Another system that has recently come upon the landscape is the Intellicell Biosciences. The advantage of these systems is that they prepare the fat graft and the fat stem cells for direct injection, thus eliminating most of the work for the technician. On the other hand, the simple liposuction technique is simple, cost effective, safe, and requires minimal learning and time investment. The total cost for this system is approximately $10-15. Fat stem cell (SVF) isolation is a process that utilizes cell washings, centrifugation, and enzymatic digestion. This process extracts the stem cells from fat producing 100-150 million stem cells per case. Typically 50 ml of fat will produce 1-2 ml of SVF. The enzyme normally used in this process is collagenase. The technique for liposuction is relatively simple. The first step is to prep the skin with Betadine and then administer a local anesthetic consisting of approximately 3 ml of 1% lidocaine and 3 ml of 1% lidocaine with epinephrine. The second step is to administer anywhere from 20 ml to 80 ml of a solution consisting of 40cc of 1% lidocaine with one amp of epinephrine in 500 ccs of saline. The amount of fluid should correspond to at least the amount of fat that needs to be harvested. The anesthesia then needs about 10-15 minutes to take effect. The next step is to make a small puncture wound in the skin using an 11-blade scalpel. Then a reusable liposuction cannula can be used to slowly aspirate the fat tissue. This needs to be performed by hand, as mechanical aspiration may be too harsh on the cells. Once the fat graft is obtained it is important to allow gravity to separate the various fluids in the graft. Gravity will pull the blood and other fluids to the bottom while the oil from the fat will float to the top. Our interest is in the middle layer of tissue. Better results will be obtained if the graft is free of whole blood, as whole blood seems to have an inhibitory effect on the regenerative process. The technique for fat stem cell extraction is the same as for liposuction, however the fat harvested (50-60 ml) is then subjected to cell washing, enzymatic digestion, and centrifugation. It is important to remember that you also need to have some fat set aside as a fat graft. The amount of fat used as a graft depends upon the joint being treated. Most tendons need no more than 3 ml of fat graft, while rotator cuff tears require 6 ml, and most joints will need 6-9 ml (with the exception of the hip, which usually accommodates only 3-6 ml of fat graft. The fat graft has two purposes, it acts as a scaffold and it supplies some adipose stem cells. Bone Marrow-Derived Stem Cells. The technique for obtaining bone marrow stem cells is a simple aspiration technique, much as a hematologist does (Fig. 10). The key to obtaining bone marrow stem cells is to adequately anesthetize the periosteum. This is usually achieved with a combination of Marcaine® and lidocaine. Once the periosteum is adequately anesthetized, a bone marrow aspiration needle is gently introduced through the periosteum, and approximately 60 ml of aspirate is removed. The aspirate then undergoes centrifugation. This will produce 7-10 ml of bone marrow aspirate concentrate (BMAC). It is very important to draw the bone marrow aspirate slowly in order to minimize the amount of blood in the concentrate. In addition, remember that the concentrate also contains PRP. The problem with BMAC is that the numbers of MSCs present dramatically diminishes with age. In a newborn 1 in every 10,000 cells is a stem cell; however by the time a person reaches their 80th birthday just 1 in every 2,000,000 cells is an MSC. Despite this, there are many other factors that make BMAC very important in the regenerative stem cell world

Bone marrow and adipose tissue are both valuable sources of stem cells, however there are significant differences between them: 1.Adipose tissue contains more MSCs than bone marrow, thus adipose tissue has the advantage in this department; 2.Adipose tissue and bone marrow have similar numbers of HSCs, but those of adipose tissue are short-lived and seem to be different from the usual HSCs. Bone marrow has more effective HSCs and essentially greater numbers. Thus, in terms of HSCs bone marrow is preferable to adipose tissue. So, should you use adipose tissue or bone marrow? The simple answer is to use both. Other Materials and Techniques that can Affect Stem Cells. Exosomes. Exosomes are becoming progressively more important in the stem cell world. Exosomes are bi-lipid membrane vesicles secreted by many different types of cells. They function as mediators of intercellular communication. Exosomes are very efficient in carrying proteins and nucleic acids, and thus are excellent for carrying various cytokines. Human Growth Hormone. Human growth hormone (HGH) has been successfully used to help grow cartilage in joints. Dunn showed that HGH will cause tissue such as cartilage to grow by injecting it intraarticularly.11 There appears to be little in the way of side effects since this is injected into the joint and the body absorbs very little. The usual dosage of HGH is 0.2 mg. Note: It is vital that you do not use HGH when treating professional athletes. Dexamethasone. Dexamethasone is injected in a dosage of 10 ng. At this low dose the dexamethasone acts as a growth factor. Calcitonin. Calcitonin nasal spray is useful when dealing with any joint problem. The calcitonin helps to stabilize bone lesions under the diseased cartilage. It also seems to help stabilize (and may help promote the growth of) articular cartilage.12,13. Hyaluronic Acid. Hyaluronic acid seems to enhance the function of stem cells in the joint.14 In this study Saw and Wallin performed a microfracture surgery (arthroscopic surgery where small holes are made in arthritic bone to allow for bleeding). One week after surgery they injected peripheral blood stem cells and 2 ml of hyaluronic acid. This mixture was injected at weekly intervals for five weeks. Biopsy results showed hyaline cartilage regeneration. Dietary Supplements. Supplements are a very important aspect of stem cell treatment. Most of these supplements will contain vitamin D3, carnosine, green tea extract, omega-3 fatty acids, Chlorella, and a host of other compounds. Do not underestimate the power of supplements as they can have potent stimulatory effects on stem cell release from the marrow. Hyperbaric Oxygen. Hyperbaric oxygen seems to mobilize stem cells in the body making them available for repair. Thom showed that hyperbaric oxygen will cause rapid mobilization of stem cell in humans.15 This mobilization is thought to be caused by a nitric oxide (NO)-dependent mechanism. Over a course of 20 treatments the output of CD34+ cells increased 8-fold. It is thought that NO synthesis in the bone marrow triggers the release of an enzyme that mediates stem/progenitor cell release. So, hyperbaric oxygen does its repair work not by providing more oxygen to the tissues but by increasing stem cell output. Supplements that increase NO production may also increase stem cell production. Arginine seems to help NO production, which in turn stimulates stem cell release. Arginine also has a direct effect on the pituitary gland and may help stimulate HGH production. One caution with arginine is that it may also cause a viral release from the body. DC Electrical Stimulation

Photomodulation. Photomodulation seems to work on both PRP and stem cell components of treatment.23 Photo modulation seems to have far ranging effects. Low-level monochromatic lights have been shown to have positive effects on wound healing and pain relief, as well as immunomodulatory and anti-infectious properties. Blue, green, and red light appears to increase the release of NO, which increases stem cell output. Blue light decreases proliferation of cells. Red and yellow light increases cell proliferation. Red light mitigates pain. Blue light has a microbiocidal effect. Photo-activated PRP produces both potent growth factors and the potent anti-inflammatory agent interleukin-1 receptor antagonist (IL-1RA), thus providing us with a PRP injection that has both healing (growth factors) and anti-inflammatory properties. Photo-activated PRP is both PRP and autologous conditioned serum. Autologous conditioned serum is very similar to a German treatment called Orthokine®. This treatment involves incubating blood in glass beads for 24-36 hours, and produces IL-1RA, among other things. At the current time I do not think that this process is allowable in the United States under current FDA guidelines. Monocytes and neutrophils are known to be the main producers of pro-inflammatory cytokines in human blood. Since cytokine content is not restored after the light-induced drop of tumor necrosis factor alpha (TNFα) and interleukin (IL)-6 levels, it is hypothesized that photo modulation blocks the synthesis of the acute phase of pro-inflammatory cytokines and most likely, simultaneously “switches on” in the synthesis of anti-inflammatory cytokines. However, the astonishingly high rate and synchronicity of the “disappearance” of some cytokines from blood plasma and the “appearance” of some others suggests that their level is determined not only by processes of synthesis, but also by some other light-induced events. It is also thought that photomodulation produces beta-endorphins from the WBCs. Another major aspect of photomodulation is the positive effect it has upon stem cell proliferation (Fig.11)

Regenerative Photonic Therapy. Regenerative photonic therapy (RPT)24 is a treatment using special forms of monochromatic lights (including laser) that are applied to damaged (pathological) tissue in a live body in order to accelerate or improve tissue repair or regenerate it to normal condition. These special forms of monochromatic light are called therapeutic optical windows (TOWs). TOWs can improve or reverse to normal various pathological tissue conditions. Several TOWs are used in one therapeutic session to improve underlying tissue pathologies. Figure 12 shows the components of RPT which include a cold laser, LED lights, and super-luminous diodes. Among other things, RPT activates cell and tissue metabolism. This activation results in the proliferation of cells, increased synthesis of ATP (the basis of all cellular energy), and increased microcirculation to the area. The products that RPT produces can be called photoceuticals as they are compounds that are produced by the effect of light. When we are describing the "healing cycle" we are including 4 distinct phases. The first is the coagulation phase. The second is the inflammatory phase. The third is the fibroblastic repair phase, and the fourth is the maturation or remodeling phase. At each phase of tissue repair specific goals are accomplished by key cells, which are controlled by specific cellular messengers. For instance, the inflammatory phase requires substantial ATP; however this may not be readily available in chronic injuries. Injuries often get “stuck” in the inflammatory phase and thus go on to be chronic injuries, but RPT helps to create the proper environment needed to deal with the inflammatory phase and actually speed up its course. RPT helps clean up the cellular debris, thus enabling the body to move on to the fibroblastic or repair phase. When someone has a painful reaction to a PRP or stem cell injection it is often due to the cellular debris and the cytokines or inflammatory factors that are released. RPT reduces the reactive oxygen species (ROS) that cause cell damage, and at the same time helps to increase NO, which helps to increase circulation, stem cell output and a host of other important cellular messengers. The products that RPT produces can be called photoceuticals, as they are compounds that are produced by the effect of light. RPT alone seems to work quite well, however when it is used in combination with PRP and stem cell injections there seems to be some great synergy

Contraindications for Stem Cell Injections. One should avoid using bone marrow stem cells in any type of bone marrow derived cancer such as lymphoma. This is because there may still be some cancer cells lurking in the bone marrow. If the patient has a history of a non-bone marrow derived cancer or has metastatic disease it is vital to check with the patient’s oncologist – even if the patient’s cancer is declared cured. These provisions do not apply when using fat derived stem cells. If the patient has anemia or other blood problems this is a relative contraindication. Also anyone with an infection should probably not be treated with either stem cells or PRP. Another thing that should be avoided is the use of cortisone. This is a relative contraindication. The use of cortisone as an intraarticular injection needs to be avoided. If the patient needs to take cortisone for a medical condition than the stem cell injection may possibly be given. Inactivity needs to be avoided. The body is able to repair itself under duress. There is no need to restrict the patient’s activity. Perhaps for a few days after the injection the patient’s pain may preclude vigorous activity but as the patient recovers activity may be resumed. It should also be mentioned that Plavix® (clopidogrel bisulfate) and Coumadin® (warfarin) are not contraindications for stem cell or PRP injections. Also, as previously stated NSAIDS are probably not a contraindication. CONCLUDING REMARKS: STEM CELLS VERSUS PRP INJECTIONS. Stem cell injections are more important in areas of low oxygen tension. The reason for this is that the bone marrow is an area of low oxygen tension. A severely arthritic joint or disc is also an area of low oxygen tension. Furthermore, areas of low oxygen tension also have limited blood supplies. Stem cells seem to thrive in these areas. However, remember that stem cells need the growth factors from the PRP in order to do their work. The best rule of thumb to follow is that stem cells of some type should be used in a joint while PRP with a fat graft should be done on tendons and similar type of problems. A more difficult question is when to use bone marrow derived stem cells (BMAC) versus fat derived stem cells (SVF). Each has its purpose. BMAC contains many different growth factors, many of which are still not discovered. BMAC does appear to contain IGF-1, while SVF does not, hence it is especially important to use HGH with SVF. BMAC probably has the same number of total stem cells but SVF contains many more MSCs. If possible, try to use both SVF and BMAC. If cost truly is a factor then consider using SFV due to the lower cost involved and the number of MSCs produced. I should say that that this is a hunch on my part and I am not able to back it up with hard evidence. Right now in the stem cell world there are two schools of thought as to whether BMAC or SVF is better for regenerative purposes. Speaking from the review of the results in our clinic, the results with SVF, a fat graft, and PRP seem to rival the results with BMAC, PRP, and fat graft. SVF seems to work faster, possibly secondary to the greater number of injected MSCs. The timeframe in which results are seen varies with the patient and the condition treated. Some results can be seen in as little as 2-weeks. Tell your patients to expect a roller-coaster effect. Some patients report that pain can leave as if a light switch were turned off. The results in the clinic exceed 85% “excellent” results after performing thousands of cases for a variety of musculoskeletal conditions. One bit of advice when one is learning is to start out slowly by first performing PRP and fat graft injections, once competency is achieved with PRP techniques then move on to the more involved techniques such as BMAC and SVF. REFERENCES. 1.Crane D, Everts AM. Platelet rich plasma (PRP) matrix grafts. Practical Pain Management. 2008;8. 2.Haynesworth S, Bruder SP, et al. Mitogenic stimulation of human mesenchymal stem cells by platelet releasate. Poster presentation at: American Academy of Orthopedic Surgery; March, 2001. 3.Bielecki TM, Gazdzik TS, Arendt J, Szczepanski T, Król W, Wielkoszynski T. Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. J Bone Joint Surg Br. 2007;89:417-420. 4.Wasterlain AS, Braun HJ, Harris AH, Kim HJ, Dragoo JL. The systemic effects of platelet-rich plasma injection. Am J Sports Med. 2013;41:186-193. 5.Jung Y, Song J, Shiozawa Y, et al. Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche. Stem Cells. 2008;26:2042-2051. 6.Mifune Y, Matsumoto T, Kawamoto A, Kuroda R, et al. Local delivery of granulocyte colony stimulating factor-mobilized CD34-positive progenitor cells using bioscaffold for modality of unhealing bone fracture. Stem Cells. 2008;26:1395-1405. 7.Matsumoto T, Kawamoto A, Kuroda R, et al. Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol. 2006;169:1440-1457. 8.Grcevic D, Pejda S, Matthews BG, et al. In vivo fate mapping identifies mesenchymal progenitor cells. Stem Cells. 2012;30:187-196. 9.Caplan AI. What's in name? Tissue Engineering Part A. 2010;16:2415-2417. 10.Vangsness C, Dellaero, Griffin DW, Farr J, Boyd JL, O'Donnell JB, Fox DL. A randomized clinical trial using mesenchymal stem cells for meniscus regeneration and osteoarthritis. AAOS 2012; Abstract 552. 11.Dunn AR. Morphoangiogenesis: a unique action of growth hormone. Microvasc Res. 2002;63:295-303. 12.Manicourt DH, Azria M, Mindeholm L, Thonar EJ, Devogelaer JP. Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis. Arthritis Rheum. 2006;54:3205-3211. 13.Manicourt DH, Altman RD, Williams JM, et al. Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions. Arthritis Rheum. 1999;42:1159-1167. 14.Saw KY, Wallin KL. Paper presented at: British Orthopedic Association Meeting; Sept, 2009: Manchester, UK. 15.Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG. Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol. 2006;290:H1378-H1386. 16.Zhao M, Song B, Pu J, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature. 2006;442:457-460. 17.Zizic TM, Hoffman KC, Holt PA, et al. The treatment of osteoarthritis of the knee with pulsed electrical stimulation. J Rheumatol. 1995;22:1757-1761. 18.Mont MA, Hungerford DS, Caldwell JR, et al. Pulsed electrical stimulation to defer TKA in patients with knee osteoarthritis. Orthopedics. 2006;29:887-892. 19.Zhao M, Bai H, Wang E, Forrester JV, McCaig CD. Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors. J Cell Sci. 2004;117:397-405. 20.Ferroni P, Roselli M, Guadagni F, et al. Biological effects of a software-controlled voltage pulse generator (PhyBack PBK-2C) on the release of vascular endothelial growth factor (VEGF). In Vivo. 2005;19:949-958. 21.Becker RO. Augmentation of regenerative healing in man. A possible alternative to prosthetic implantation. Clin Orthop Relat Res. 1972;83:255-262. 22.Cheng N, Van Hoof H, Bockx E, et al. The effects of electric currents on ATP generation, protein synthesis, and membrane transport of rat skin. Clin Orthop Relat Res. 1982;171:264-272. 23.Tuby H, Maltz L, Oron U. Photomedicine and Laser Surgery. 2009;27:227-233. 24.Salansky N, Salansky N. Regenerative photonic therapy. Silicon Valley Engineering Council Journal. 2011;105-120. ABOUT THE AUTHOR

Chapter 16. Update on the Pathogenesis and Comorbidities Associated with Chronic Obesity. Dr. Ron Shane, ND, Ph.D., OMD, MFA; Dennis Lox M.D.; Dr. Kurt Bivens; Justin Tang; assisted by: Grace Sahyouni, Winnie Chung, Alva Liang, Kevin Yang, Benjamin Lee, Paramveer Birring, Akshay Hingorani, and Regina Woo. INTRODUCTION

BIOLOGICAL BASIS OF OBESITY

PROFOUND HEALTH IMPLICATIONS OF OBESITY

Medical Consequences

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 17. Mind and Body Strategies to Further Induce the Beauty of the Face and Torso. Dr. Ron Shane, ND, Ph.D., OMD, MFA; assisted by Alva Liang. INTRODUCTION

THE NOTION OF BEAUTY

The Obesity Effect

MEDICAL STRATEGIES

ABOUT THE AUTHOR

Chapter 18. Pulsed Electromagnetic Field Therapy with Mark II Coil for Diabetic Neuropathy. C. Norman Shealy, M.D., Ph. D

ABSTRACT

INTRODUCTION

DISCUSSION

RESEARCH AND DESIGN

RESULTS

DISCUSSION

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 19. How to Maintain Memory at Any Age. Pamela W. Smith, M.D, MPH, MS

ABSTRACT

INTRODUCTION

HOW TO MAINTAIN MEMORY AND PREVENT COGNITIVE DECLINE

Remove or Reduce Exposure to Toxic Substances

Stress Reduction

Lifestyle – Unhealthy Habits

Hormone Decline and Imbalance

Inflammation

Other Factors that Affect Cognition and Memory

Brain Nutrients

DHA

Phosphatidylserine

Glyceryl-phosphoryl-choline

Ashwagandha

Blueberry Extract

Grape Seed Extract

Vinpocetine

Ginger

Ginkgo Biloba

Coenzyme Q10

Boron

Acetyl-L-Carnitine

Alpha Lipoic Acid

Carnosine

Zinc

Huperzine A

Dimethylaminoethanol (DMAE)

Curcumin

B Vitamins

Vitamin E

S-Adenosyl Methionine (SAMe)

Lemon Balm

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

Chapter 20. Methylation's Role in Neurological Health, Aging & Recovery: Beyond Methylenetetrahydrofolate Reductase (MTHFR) Deficiency. Kendal Stewart, M.D

ABSTRACT

INTRODUCTION

METHYLATION'S ROLE IN NEUROLOGICAL HEALTH, AGING & RECOVERY. The Biochemistry of Methylation

Methylation Deficiency. Methylenetetrahydrofolate Reductase Polymorphisms

The Homocysteine Quandary

Folic Acid Autoantibodies

The Bucket Theory of Methylation

Recovery. Clinical Evaluation of Patients with Suspected Methylation Deficiency

Optimizing Neurological Health and Aging

CONCLUDING REMARKS

ABOUT THE AUTHOR

Chapter 21. Peptides as an Alternative to Bioidentical Hormone Replacement Therapy. Jose Vazquez-Tanus M.D

ABSTRACT

INTRODUCTION

USING PEPTIDES TO REVERSE AGING

PEPTIDES: AN INTRODUCTION

Classification of Peptides

How do Peptides Work?

BENEFITS OF PEPTIDE THERAPY

CONCLUDING REMARKS

RECOMMENDED READING

ABOUT THE AUTHOR

Chapter 22. The Critical Role of Iodothyronine Deiodinase Enzymes in the Regulation of the Thyroid System. Denis Wilson, M.D. ABSTRACT

INTRODUCTION

IODOTHYRONINE DEIODINASE ENZYMES AND THYROID HORMONE

CONDITIONS ASSOCIATED WITH HYPOTHYROIDISM

OPTIMIZING T4 TO T3 CONVERSION TO TREAT HYPOTHYROIDISM. Lifestyle Changes

The Supportive Power of Herbs and Nutrients

Treatment with T3

T4-Treated Patients

Effect of Treatment on T4, TR3, and T3 Levels

Essential Concepts for T3 Treatment

Treatment Protocol

How to Order Sustained Release T3

CONCLUDING REMARKS

REFERENCES

ABOUT THE AUTHOR

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President, American Academy of Anti-Aging Medicine (A4M)

Historian Alan Kay remarked that: “The best way to predict the future is to invent it." The A4M demonstrates future-forward innovative thinking that has not merely withstood the tests of time and scrutiny, but has flourished and proliferated into a viable model now embraced around the world.

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Patient received sessions every 2-weeks with individual frequencies and pre-set programs. Just 3-months later, patient’s thrombosis was barely visible on the echocardiogram and patient was taken off the Coumadin medication. Patient successfully avoided having to go through open-heart surgery by adding biofeedback & focused field stimulation therapy to the existing treatment protocol. According to pediatric cardiologist Aaron Levine, M.D. Children’s Hospital at Westchester Medical Center, who stated in his letter dated October 2003 to the patient’s pediatrician:

“The thrombus as described in previous letters by Dr. Woolf is not clearly seen at this examination”.

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