Self-Perpetuating Neuroendocrine-Immune Stress Response

1. Self-Perpetuating Neuroendocrine-Immune Stress Response Sponsored by Apex Energetics by Datis Kharrazian, D.C., M.S. Fellow of the American Academy Chiropractic Physicians Diplomate American Board of Clinical Nutrition Diplomate of the Board of Nutrition Specialists Diplomate of the International Board of Applied Kinesiology

2. Goals of this Presentation Understand the advanced concepts of central modulation of the Hypothalamus-Pituitary-Adrenal Axis. Review the vicious cycles that take place with the Neuroendocrine Immune Response to Stress. Understand the concepts of inflammation and neuronal plasticity of the HPA axis.

3. Understand the Advanced Concepts of Central Modulation of the Hypothalamus-Pituitary-Adrenal Axis.

4. Hippocampus HPA Axis PARAVENTRICULAR NUCLEUS Cerebral Cortex Basal Ganglia Mesencephalic Nucleus Raphe Magnus Pontomedullary Reticular Formation Cerebellum Locus Ceruleus Nucleus Tract Solitaris

5. Review the vicious cycles that take place with the Neuroendocrine Immune Response to Stress.

6. Summary of Biochemistry of Stress (Endocrine and Immune) Decreased expression of insulin receptor site signal translocation of GLUT transporters Increased expression of interleukin-6 and interleukin 10 Increased production and sensitivity of IL-6 receptor complexes (sIL-6R) Suppressed production of IL-12 and interferon gamma Increased expression of tumor necrosis factor-alpha Increased hypothalamus-pituitary-adrenal axis activation Decreased production of IGF-1 and HGH Decreased insulin secretion Suppression of LH in men and women Suppression of SIgA Decreased testosterone in males Altered progesterone distribution in females Altered expressions of leptin on neuropeptide Y and hypothalamic integration Negative nitrogen balance Mineral depletion (zinc, cobalt, selenium, copper)

7. Suppressed neutrophil function Suppressed lymphocyte count and proliferation Suppressed natural killer cell count and activity Alterations in polymorphonuclear cell priming potentials Shift of T helper lymphocytes (TH) to TH2 over TH1 balance which results in the up-regulation of humoral immunity and down-regulation of cell-mediated immunity Elevations of urea Elevations of C-reactive protein Increased production of PGE2 via expression of inducible cyclo-oxygenase 2 Uncoupling of mitochondria oxidative phosphorylation Increased uric acid production Decreased iron, hemoglobin, ferritin, TIBC Reduced glutamine levels Elevated creatine kinase Altered catecholamine production and secretion Decreased serum tryptophan levels Alteration in brain serotonin levels Neurotransmitter release and/or membrane sensitivity is altered Autonomic shifts of balance into what is called either sympathetic or parasympathetic syndromes Alterations in fatty acid metabolism which decrease the chain length of fatty acids which may be attributed to either alterations in synthesis or higher rates of peroxidation

8. Activation of HPA Axis Increase GALT Activity Up-Regulate 17,20 Lyase in Women Increase activity of IL-1, TNF Up-Regulate Aromatase in Males Decrease SIgA TH-1 Subset Dominance TH-2 Subset Depression Increase ACTH Receptor Sites Up-Regulate COX-2 Decreased Humoral Response Metabolic Disorders Increase production of Prostaglandin 2 and 4, Leukotriens Prostanoids, Arachadonic Acid Dysglycemia Mitochondria Uncoupling Switched Metabolism Essential Fatty Acid Shifts Glial Cell Activation Depletion of Glutathione Decreased Neurological Integration Lipid Perioxidation Oxidative Stress Down-Regulate Alter Phase I and II Detoxification 5� Diodinase Decreased ATP THYROID DYSFUNCTION INTESTINAL INFLAMMATION DETOXIFICATION DYSGLYCEMIA

10. Hippocampus Destruction Suppressed Pituitary Axis Altered GI Function Increased IL-6 and sIL-6R Up-regulation of HPA Axis Suppressed Immunity Inflammation Oxidative Stress Decreased Glutamine Hyperinsulinemia EFA Metabolic Shifts

11. HPA Axis Activation Suppresses LH MALES FEMALES LOW TESTOSTERONE LOW PROGESTERONE

12. Insulin Resistance and Andropause Vicious Cycle Insulin Resistance up-regulate aromatase conversion of testosterone to estradiol abnormal testosterone: estradiol ratio

13. Insulin Resistance and PCOS Vicious Cycle Insulin Resistance up-regulate 17,20 lyase increased production of testosterone

14. Pregnenolone Steal

15. Development of T Helper Cells Immature T Cell (T Helper -0) IL-12 IL-4 TH-1 Lymphocytes TH-2 Lymphocytes IL-2, IFN, TNF IL-4, IL-5, IL-6, I10, IL-13 MACROPHAGES B CELLS Cell Mediated Immunity Humoral Immunity

16. Cortisol Activation Insulin Resistance Elevated Estrogen In Males Decreased TH-1 Elevated Testosterone In Females Decreased TH-2 Decrease SIgA Leaky Gut Dysbiosis / Impaired Detoxification

17. Understand the Concepts of Neurogenic Inflammation and Neuronal Plasticity of the HPA axis. 

18. Hippocampus HPA Axis PARAVENTRICULAR NUCLEUS Cerebral Cortex Basal Ganglia Mesencephalic Nucleus Raphe Magnus Pontomedullary Reticular Formation Cerebellum Locus Ceruleus Nucleus Tract Solitaris

19. IL-6 Time Dependent Sensitisation Time Dependent Sensitisation is described as a progressive and persistent amplification of behavioral, endocrine and immunological responses to repeated intermittent stimuli over time. Plasma sIL-6R and IL-6 concentrations are elevated in inflammatory disorders, in psychological stress and pathogenic infections.

20. Neuroimaging Changes with Chronic HPA Axis Activation

21. Cortisol/Hippocampus Vicious Cycle Hippocampus Cell Destruction  Elevated CRH Elevated ACTH Elevated Cortisol

22. Hippocampus HPA Axis PARAVENTRICULAR NUCLEUS Cerebral Cortex Basal Ganglia Mesencephalic Nucleus Raphe Magnus Pontomedullary Reticular Formation Cerebellum Locus Ceruleus Nucleus Tract Solitaris

23. Neuorgenic Inflammation

24. Mechanism of Neurogenic Inflammation Plasticity of the HPA Axis Increase IML Activity Increased Catacholamine Release Depolarization of C-Fibers Release of Neuropeptide Substance P Tissue Inflammation

25. Mechanisms for Chronic Gastrointestinal Inflammation Antigen Mediated Non-Antigen Mediated Sensitivities - HPA Stress Response Parasites Bacterial Yeast Viral

26. Winding Down the Neuroendocrine-Immune Axis STEP 1 � Modified Fast STEP 2 � Clearvite program with supplements STEP 3 � Provocation phase

27. Metabolic Assessment Form

28. Baseline Support for Winding-Down Neuroendocrine-Immune Axis 1. ADAPTOCRINE: (K-2): 2 capsules, three times a day with meals 2. ADRENACALM (K-16): �- � teaspoon applied three times a day as directed 3. OXICELL (K-22): � teaspoon applied three times a day as directed 4. X-VIROMIN (K-31): two capsules, 3x a day with meals

29. With Insulin Resistance Add: 1. GLYSEN (K-1): 2 capsules, three times a day with meals 2. OMEGACO-3 (K-7): 2 tablespoons, 2x a day with or without meals 3. FIBROMIN (K-25): 2 capsules, 3x a day with or without meals 4. PROTOGLYSEN (K-28): 2 capsules, 3x a day with meals

30. With Hypoglycemia Add: 1. PROGLYCO-SP (K-13): 2 capsules, three times a day with meals 2. SUPER EFA COMPLEX (K-8): 2 tablespoons, 2x a day with or without meals 3. ADRENASTIM (K-15): �- � teaspoon applied three times a day as directed

31. Note: If the patient has symptoms of both reactive hypoglycemia and insulin resistance support them for insulin resistance.

32. With Thyroid Imbalance Add: 1. THYRAXIS-PT (K-30): 2 capsules, 3x a day with meals 2. THYROCNV (K-9): 2 capsules, 3x a day with meals

33. With Liver Detoxification Need Add: 1. METACRIN-DX (K-10): 2 capsules, 3x a day with meals 2. BILEMIN (K-11): 2 capsules, 3x a day with meals

34. With Male Andropause Add: 1. OPTICRINE (K-3): 2 capsules, 3x a day with meals 2. TESTANEX (K-17): �- � teaspoon applied three times a day as directed

35. With Female Menstrual Irregularities Add: 1. PROGESTAID (K-4): 2 capsules, 3x a day with meals