Curso sobre Terapia de Corrección Metabólica, Neurológica y Diabetes by Semal

Curso de Dos Días: Terapia de Corrección Metabólica. Two Days Course: Metabolic Correction Therapy

Terapia de Correción Metabolica: Cambiando el paradigma del cuidado de la Salud. Metabolic Correction Therapy: Changing the healthcare management paradigm Cáncer y enfermedades infecciosa y neurometabólicas. Cancer, Infectious and Neurometabolic Diseases. Metabolic Correction Institute © 2015-2016 All Rights Reserved Part.1 o gotype

Saludos Estimados médicos, educadores e investigadores clínicos: Las guías médicas dan al clínico herramientas terapéuticas que han sido evidenciadas, pero muchas veces los resultados obtenidos con estas estrategias están por debajo de las expectativas deseadas. A veces, las guías médicas alcanzan alivio sintomático o el control de los factores de riesgo, pero no necesariamente la mejoría o cura del paciente. Sin embargo, un análisis exhaustivo pueden revelar importantes factores etiológicos en determinados individuos que pueden utilizarse para corregir problemas no anteriormente detectados y que al corregirlos pueden lograr mejores resultados terapéuticos. El concepto de corrección metabólica fue introducido por primera vez en 2011 como una manera de proponer un enfoque terapéutico seguro para llegar más allá del remedio sintomático para reconocer y manejar las anomalías bioquímicas causantes de enfermedades específicas. Las reacciones bioquímicas en nuestro cuerpo dependen usualmente de la disponibilidad de los precursores y enzimas metabólicas. Para alcanzar un estado fisiológico sano, el organismo requiere que las reacciones bioquímicas se producen a una velocidad controlada que produce el equilibrio saludable. Una compleja interacción de múltiples variables pueden alterar este equilibrio. La interacción entre la composición genética, los patrones dietéticos, traumatismos, enfermedades, toxinas, medicamentos y factores de estrés ambiental puede elevar la demanda de los nutrientes necesarios para alcanzar este equilibrio metabólico óptimo. En este curso se reunirá el marco teórico, el enfoque práctico y la evidencia para hacer frente a varios aspectos importantes en el paciente con cáncer, las enfermedades infecciosas y trastornos seleccionados neurometabólicos seleccionados. Con el fin de restablecer el equilibrio fisiológico saludable en diferentes condiciones médicas, se discute, acorde con la documentación valida, las causas con las pruebas de laboratorio fiable en forma detallada. Las pruebas además de los parámetros clínicos habituales incluyen el reconocimiento de los contaminantes orgánicos persistentes, metales pesados, los desequilibrios nutricionales específicos, desregulaciones inmunes, infecciones crónicas, las pruebas genómicas y otros. Vamos a discutir la gestión específica de estos importantes factores. Estas estrategias terapéuticas pueden producir mejoras significativas en los resultados de individuos concretos.

Jorge R. Miranda-Massari, Catedrático Director, Metabolic Correction Therapy Course

Greetings Dear Clinicians, Clinical Educators and Researchers:

Standard medical guidelines provide clinicians with therapeutic tools that have been well studied, but many times the outcomes achieved with these strategies are below the desired expectations. Sometimes, medical guidelines achieve at most symptomatic relief, or control, of risk factors. However, comprehensive examinations can reveal important etiological factors in specific individuals that when effectively treated can have an important effect achieving better outcomes. The concept of metabolic correction was first introduced in 2011 as a way of proposing a safe therapeutic approach that would go beyond symptomatic remedy to address the underlying biochemical abnormalities related to specific illnesses. Biochemical reactions in our body depend usually on the availability of precursors and metabolic enzymes. To achieve a healthy physiological state, the organism requires that biochemical reactions occur at a particular controlled rate that produces a healthy equilibrium. Complex interactions of variables can alter this meticulous equilibrium. The interaction between the genetic makeup, dietary patterns, traumas, diseases, toxins, medications, and environmental stressors can elevate the demand for the nutrients needed to reach this optimal metabolic equilibrium. In this course we bring together the theoretical framework, the practical approach and research evidence to deal with various important aspects in Cancer patients , selected infectious conditions and particular neurometabolic disorders. In order to re-establish healthy physiology in many of these conditions, documentation of causes with detailed reliable laboratory testing is required and will be discussed in the course. The testing besides the usual clinical parameters includes, persistent organic pollutants, heavy metals, specific nutrient imbalances, immune dysregulations, chronic infections, genomic testing within others factors. We will discuss the specific management of these significant factors. It is expected these therapeutic strategies, which will be presented in the course, may be used to produce significant improvements in clinical outcomes of individuals.

Professor Jorge R. Miranda-Massari Director, Metabolic Correction Therapy Course

TABLE OF CONTENTS DIA 1 (DAY 1) 1. Identificando y Reduciendo Riesgos para el desarrollo Cáncer (Identifying & Reducing Cancer risks) 1.1. Epidemiología de las toxinas y cáncer iatrogénico (Epidemiology of toxins and iatrogenic induced cancer) 1.2. Disfuncióon Mitocondrial (Mitochondrial dysfunction) 1.2.1. Dieta – metabolismo, mitocondria y sistema inmunológico and immune system (diet,metabolism, mitocondria and Immune system) 1.2.1.1.

Perfil de macronutrientes (macronutrients profile)

1.2.1.2.

Perfil de micronutrientes (micronutrients profile)

1.2.1.3.

Sensitividades y alergias nutricionales (Food allergies and sensitivities)

1.2.2. Infección, inflamación y mitocondria. (Infection, inflammation and mitocondria) 1.2.3. Metales pesados y mitocondria. (Heavy metals and mitocondria) 1.2.4. Contaminantes orgánicos (Organic pollutants) 1.3. Epigenética y vías Metabólicas secundarias en la regulación de diferenciación del cáncer. (Epigenetics and metabolic Pathways and molecular regulation in Cancer) 1.4. Daño y reparación del DNA (DNA damage & repair) 1.4.1. Micronutrientes/contaminantes/infeciones (Micronutrients/contaminants/ infection) 1.5. Estilos de vida (Lifestyle) 1.5.1. Dieta (Diet) 1.5.2. Ejercicio (Exercise) 1.5.3. Descanso (Rest) 4 Metabolic Correction Institute © 2015-2016 All Rights Reserved o gotype

1.5.4. Ambiente del hogar (Home environment) 1.5.5. Ambiente de trabajo (Work environment) 1.5.6. Espiritualidad (Spirituality) 1.5.7. Otros factores (Others Factors ) 1.6. Pruebas de laboratorio (Laboratory testing) 1.6.1. Pruebas genóomicas (Genomic testing) 1.6.2. Panel de micronutrients (Micronutrient panel) 1.6.3. Marcadores de cáncer (Cancer tumor markers) 1.6.4. Marcadores Metabólicos (Metabolic Markers) 1.6.5. Panel de hormonas (Hormone panel) 1.6.6. Panel de enfermedades infecciosas (Infectious disease panel) 1.6.7. Panel de metales pesados (Heavy metals panel) 1.6.8. Contaminantes orgánicos (Organic contaminants 2. Historial avanzado y examen físico completo en el manejo de pacientes con cáncer (Advanced history and complete physical exam for management in cancer patients) 3. Pruebas de laboratorio y aplicaciones clínicas en el paciente con cáncer. (Advanced clinical laboratory testing and clinical applications for patients with cancer) 4. Manejo Avanzado de Vitamina C en Cáncer y otras terapias intravenosas (Advanced Vitamin C and other IV treatments in Cancer) 5. Manejo Metabólico Comprensivo en el manejo del paciente con cáncer (Comprehensive Metabolic therapies in Cancer Management) 5.1. Dieta (diet) 5.2. Oral Supplements (Suplementos Orales) 5.3. Oral Medications (Medicamentos orales) 5 Metabolic Correction Institute © 2015-2016 All Rights Reserved o gotype

6. Manejo del dolor (Pain management) 6.1. Consideraciones dietarias (Dietary considerations ) 6.2. Supplementos (Supplements) 6.3. Medicamentos (Medications ) 7. IVC and infectious diseases (IVC y enfermedades infecciosas)

Formatted: Spanish (International Sort)

7.1. Viral Infections (i.e., herpes, varicela zoster, EBV, dengue, chikungunya) (Enfermedades virales, i.e., herpes, varicela zoster, EBV, dengue, chikungunya) 7.2. Bacterial Infections (i.e., mycoplasma pneumonia, Lyme Borrelia) Infecciones Bacterianas (i.e., mycoplasma pneumonia, Lyme Borrelia) 8. Oxidative therapies for infections and tissue repair (terapia oxidative para infecciones y reparacion tisular) 8.1. Ozone Ozono (ozone) 8.2. HBO Oxigeno hiperbárico (HBO) 8.3. Suplementación de Oxigeno (Supplemented oxygen ) 9. References Referenciass Reference s)

DIA 2 (DAY 2) 10. Corrección Metabólica de las neuropatías y desordenes Neurometabólicos. (Metabolic Correction of neuropathies and neurometabolic disorders) 11. Corrección Metabólica y Mitochondrial en Oftalmologia. (Metabolic and Mitochondrial Correction in Ophtalmology) 11.1.

Degeneración macular (Macular degeneration )

11.2.

Glaucoma (glaucoma)

11.3.

Retinopatia diabetica (Diabetic Retinopathy)

12. Múultiple sclerosis (Multiple Sclerosis) 13. Espectro Autista (Autism Spectrum Disorder)

1. Identifying & Reducing Cancer risks

1.1. Epidemiology of Toxins in Chronic Disease and Cancer. The World Health Organization has informed that chronic, non-infectious diseases are rapidly becoming epidemic worldwide. Growing rates of neurocognitive, metabolic, autoimmune, cardiovascular diseases and cancer cannot be attributed only to genetics, lifestyle, and nutrition. It is now increasingly recognized that early life and chronic exposures, of toxicants may also cause 1 chronic disease. The President's Cancer Panel reported in 2010 that "the true burden of environmentally induced cancers has been grossly underestimated" and strongly urged action to reduce people's widespread exposure to carcinogens. The panel advised the President "to use the power of his office to remove the carcinogens and other toxins from our food, water, and air that increases health care costs, decreases our 2 productivity, and devastate American lives." Understanding about the role of toxic chemicals, nutritional imbalances, on the development of many chronic is important to design more effective treatments. Exposures to toxic or endocrinedisrupting chemicals can influence metabolism, alter brain growth and play a substantial role in the developing of respiratory diseases, neurobehavioral disorders, mental disorders; obesity and type 2 3 diabetes and cancer.

Formatted: Spanish (Puerto Rico)

Several underlying mechanisms of deregulated cellular energetics are associated with mitochondrial dysfunction caused by mitochondrial DNA mutations, mitochondrial enzyme defects, or altered oncogenes/tumor suppressors. Moreover, defects in mitochondrial enzymes are associated with both 4 familial and sporadic forms of cancer. Dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established 5 aspects of cell growth and stress response. Metabolic enzymes of the Krebs cycle have been newly recognised as oncosuppressors. Recent studies on indicate that modulation of mitochondrial respiration may induce an arrest of cancer cell proliferation and differentiation and/or or death. This suggests that manipulation of some mitochondrial 6 activities may induce anticancer effects.

1.3. Epigenetics, Metabolic Pathways and Molecular Regulation in Cancer Epigenetics is the study of changes in gene expression that does not involve changes to the underlying DNA sequence but that influences how cells read the genes. Epigenetic change can be influenced by factors such age, the environment, lifestyle, and disease state. The metabolic alterations produced by intake of some nutrients, drugs and chemicals can occur by 7 directly a impact on epigenetic regulation. The growing understanding how metabolic pathways are affected by environmental and genetic factors is

1.2. Mitochondrial Dysfunction Cancer has been postulated as an energy problem caused by a mitochondrial metabolic disease.

expected to provide innovative insights for the treatment of many diseases. New technology will enable the analysis of large groups of complex molecular and clinical data for understanding how inflammation and mitochondria affect bioenergetics,epigenetics and health. Energy utilization and disease are intimately connected by epigenetics. The improved interpretation of the metabolo-epigenetic data of disease will facilitate therapeutic targeting linking nutritional toxicity and metabolism. Multiple molecular mechanisms interact to modulate central cellular metabolism and provide support for the three basic needs of dividing cells: rapid ATP generation to maintain energy status; increased biosynthesis of macromolecules; and reinforced 8 maintenance of appropriate cellular redox status. To meet these necessities, cancer cells acquire modifications to the metabolism of all four major classes of macromolecules: carbohydrates, proteins, lipids and nucleic acids. In the case of cancer cells, these adaptations must be implemented in the stressful and dynamic microenvironment of the solid tumor, where concentrations of crucial nutrients such as glucose, glutamine and oxygen are spatially and 9 temporally heterogeneous.

compromise of intrinsic apoptotic function. Alterations in cancer glucose metabolism include the Warburg effect, leading to a shift in metabolism away from aerobic respiration toward glycolysis, even when sufficient oxygen is present to support respiration. 10 Such alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and proliferation. Mutations in specific metabolic enzymes, have been linked to human cancer. Mitochondrial ROS may contribute to cancer via DNA damage and the activation of aberrant signaling pathways. ROS-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF) may be a particularly important event for tumorigenesis. 11 Compromised function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis, tumor metastasis, and chemoresistance. Each of the major mitochondrial processes is linked. Therefore, the use on nutrients to improve or normalize the abnormal pathways that lead to carcinogenesis, cell proliferation and the restoration of apoptosis can represent potential valuable therapeutic tools.

Cancer development involves genetic and epigenetic alterations. Genetic marks are permanent, whereas epigenetic marks are dynamic, change with age, and are influenced by the external environment. Thus, epigenetics provides a link between the environment, diet, and cancer development. Proper food selection is imperative for better health and to avoid cancer and other diseases. Nutrients either contribute directly to cancer prevention or support the repair of genomic and epigenomic damage caused by exposure to cancer-causing agents such as toxins, free radicals, radiation, and infectious agents. Nutritional epigenomics provides an opportunity for cancer prevention because selected nutrients have the potential to reverse cancer-associated epigenetic marks in different tumor types. A number of natural foods and their bioactive components have been shown to have methylation-inhibitory and deacetylation-inhibitory properties. Mitochondrial function may contribute to cancer through alterations in glucose metabolism, the production of reactive oxygen species (ROS) and

and adiponectin, altered levels of hormones and growth factors (insulin, insulin-like growth factor-1, estrogens, and androgens), insulin resistance, and PI3K-AKT-mTOR signaling pathway alterations.

Diet/Supplementation

1.4. DNA Damage and Repair in Cancer. The relevance of DNA damage and repair to carcinogenesis became evident when it was recognized that all agents that cause cancer (carcinogens) also cause a change in the DNA 12 sequence and thus are mutagens. All the effects of carcinogenic chemicals on tumor production can be accounted for by the DNA damage that they cause and by the errors introduced into DNA during the cellsâ&#x20AC;&#x2122; efforts to repair this damage. Likewise, ultraviolet (UV) radiation and ionizing radiation can modify DNA, and also cause cancer in animals and can transform normal cells in culture into rapidly proliferating, cancer-type cells.

Despite the demonstrated benefit of healthy eating habits in cancer survivors, studies suggest that approximately 50%â&#x20AC;&#x201C;70% of survivors do not meet the current dietary guidelines. Glycemic load has been documented to impact disease free and overall survival in stage III colon cancer patients, with higher dietary glycemic load significantly associated with worse disease-free survival among overweight or 14 obese colon cancer survivors. The use of dietary supplements in cancer has not been advocated in official guidelines, but there is a number of clinical trials have demonstrated value in various aspects of cancer management such as, correcting nutrient insufficiencies, decreasing adverse effects of 15 chemotherapy, and improving quality of life. Dietary supplements also can be utilized to improve various metabolic derangements such as mitochondrial dysfunction, reduce toxicities, reduce inflammation, improve immune function, reduce oxidative stress all of which have potential benefits in various stages of cancer ranging from tumorigenesis to symptom improvement.

1.5. Life Style Lifestyle factors (diet, body weight, physical activity, and smoking) have been linked to a higher risk of much medical comorbidity (cardiovascular, metabolic, etc.). There is increasing evidence linking these factors to the risk of developing cancer and 13 likely cancer-related outcomes.

Obesity Excess body weight is a risk factor for multiple cancers. Various molecular mechanisms have been put forth to explain the association between body weight and cancer risk, including the impact of lowgrade chronic inflammation, elevated levels of leptin

1.6 Laboratory Testing Laboratory tests in patients suspected to have cancer may include blood or urine analysis and/or biopsy of a suspicious area, to assist in the arrival of the correct diagnosis. The samples may show cancer cells, proteins or other substances made by the cancer cells. Blood tests can also reflect the functionality of certain organ systems and well as other variables that affect the process of carcinogenesis, cell proliferation and metastasis.

alcohol, tobacco, heavy metals, pesticides, organic 16 compounds and many others.

Helpful Laboratory Testing for Cancer     

Optimal clinical laboratory testing is a crucial tool for prevention, early detection and monitoring of chronic conditions. In addition, optimal clinical lab testing should be used in an attempt to define the underlying causes of the condition.

 

Risk factors for cancer include interactions of variables such as age, genetic background exposure to certain chemicals and specific physiologic processes such as Chronic Inflammation, Hormones, Immunosuppression, Infectious Agents, Obesity and Radiation. Chemicals can include



TK1 Tumor Markers Genomic Testing  IL-28 Inflammation panel Environmental toxins  Heavy metals  Pesticides Infection panel Nutrient Panel  Vitamins/Minerals Organic acid testing  Mitochondrial function (OATS) Hormones  Adrenal  Thyroid  Sex

Metabolic Correction Characteristics:  Preventive  Coordinated  Evidence-based  Optimizes physicians’ treatment decisions making process  Proactive and participatory, engaging patients in lifestyle choices  Active health maintenance to compensate for genetic susceptibilities Metabolic correction therapy: Changing the healthcare management paradigm DOI: 10.15761/IFNM.1000143

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S.H. Reuben for the President's Cancer Panel, US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Reducing Environmental Cancer Risk. What We Can Do Now, 2010, http://deainfo.nci.nih.gov/advisory/pcp/annualReports/pcp08-09rpt/PCP_Report_08-09_508.pdf. 3

Sly PD, Carpenter DO, Van den Berg M, et al.Health Consequences of Environmental Exposures: Causal Thinking in Global Environmental Epidemiology. Ann Glob Health. 2016;82(1):3-9. 4

Hsu CC, Tseng LM, Lee HC. Role of mitochondrial dysfunction in cancer progression. Exp Biol Med. 2016;241(12):1281-95.

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Harrelson JP, Lee MW. Expanding the View of Breast Cancer Metabolism: Promising Molecular Targets and Therapeutic Opportunities. Pharmacol Ther. 2016. pii: S0163-7258(16)30139-5. 9

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National Cancer Institute, NIH. Center causing substaces in the environment. http://www.cancer.gov/about-cancer/causesprevention/risk/substances