SelfPerpetuating NeuroendocrineImmune Stress Response

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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

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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.

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Understand the Advanced Concepts of Central
Modulation of the Hypothalamus-Pituitary-Adrenal
Axis.
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• 
  Hippocampus
• HPA Axis
• PARAVENTRICULAR NUCLEUS
• Cerebral Cortex
  Basal Ganglia
• Mesencephalic Nucleus Raphe Magnus
• Pontomedullary Reticular Formation
  
• 
  Cerebellum
• Locus Ceruleus
• Nucleus Tract Solitaris

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

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• 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

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• 
  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

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• 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

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• HPA Axis Activation Suppresses LH
• MALES FEMALES
• LOW TESTOSTERONE LOW PROGESTERONE

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Insulin Resistance and Andropause Vicious Cycle

• Insulin Resistance
• up-regulate aromatase
• conversion of testosterone to estradiol
• abnormal testosterone estradiol ratio

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Insulin Resistance and PCOS Vicious Cycle

• Insulin Resistance
• up-regulate 17,20 lyase
• increased
  production of testosterone

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Pregnenolone Steal
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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

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• 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

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Understand the Concepts of Neurogenic
Inflammation and Neuronal Plasticity of the HPA
axis.
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• 
  Hippocampus
• HPA Axis
• PARAVENTRICULAR NUCLEUS
• Cerebral Cortex
  Basal Ganglia
• Mesencephalic Nucleus Raphe Magnus
• Pontomedullary Reticular Formation
  
• 
  Cerebellum
• Locus Ceruleus
• Nucleus Tract Solitaris

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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.

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Neuroimaging Changes with Chronic HPA Axis
Activation
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Cortisol/Hippocampus Vicious Cycle

• Hippocampus Cell Destruction
• Elevated CRH
• Elevated ACTH
• Elevated Cortisol

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

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Neuorgenic Inflammation
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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

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

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Winding Down the Neuroendocrine-Immune Axis

• STEP 1 Modified Fast
• STEP 2 Clearvite program with supplements
• STEP 3 Provocation phase

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Metabolic Assessment Form
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Baseline Support for Winding-Down
Neuroendocrine-Immune Axis

• 1. ADAPTOCRINE (K-2) 2 capsules, three times a
  day with meals
• 2. ADRENACALM (K-16) ¼- ½ teaspoon applied three
  times a day as directed
• 3. OXICELL (K-22) ½ teaspoon applied three times
  a day as directed
• 4. X-VIROMIN (K-31) two capsules, 3x a day with
  meals

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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

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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) ¼- ½ teaspoon applied
  three times a day as directed

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

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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

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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

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With Male Andropause Add

• 1. OPTICRINE (K-3) 2 capsules, 3x a day with
  meals
• 2. TESTANEX (K-17) ¼- ½ teaspoon applied three
  times a day as directed

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With Female Menstrual Irregularities Add

• 1. PROGESTAID (K-4) 2 capsules, 3x a day with
  meals