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RENEWING
THE AGING BRAIN
Presented by BRANDON BROCK,
RN, BSN, MSN/FNP, DC, DACNB, FACFN,
FABES, FABVR, FICC, RNCST, CNCT
Written by DATIS KHARRAZIAN,
DC, DHSc, MS, MNeuroSci,
Associate Professor of Clinical Neurology - Carrick Institute
Fellow of the American College of Functional Neurology
Fellow of the American Board of Vestibular Rehabilitation
Fellow of the American Academy of Chiropractic Physicians
Diplomate of the American Board of Clinical Nutrition
Diplomate of the Board of Nutrition Specialists
Diplomate of the International Board of Applied Kinesiology
Diplomate of the American Board of Chiropractic Neurology
Copyright © 2011 Datis Kharrazian. All Rights Reserved. Copyright © 2011, Datis Kharrazian. All Rights Reserved.
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2. INTENDED USE STATEMENT
The content of this course is intended for informational purposes only. The medical
information in this course is intended as general information only and should not
be used in any way to diagnose, treat, cure, or prevent any disease. The goal of
this course is to present and highlight nutritionally significant information, and
offer suggestions and protocols for nutritional support and health maintenance.
Homeopathic protocols are intended for use in symptom relief and OTC indications
only.
It is the sole responsibility of the user of this information to comply with all local
and federal laws regarding the use of such information, as it relates to the scope
and type of user’s practice.
The nutritional protocols and suggestions presented in this course are based on
the presenter’s clinical experience and research and are not intended to represent
any claims regarding product performance or benefits by the manufacturer, its
distributors, or the sponsors of this seminar.
Statements regarding nutritional products in this seminar have not been evaluated
by the Food and Drug Administration. Nutritional products presented in this
seminar are not intended to diagnose, treat, cure, or prevent any disease.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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3. DISCLAIMER AND NOTICES
The information and recommendations outlined in this presentation are not intended as a
substitute for personalized medical advice. The presentation proposes certain theoretical
methods of nutrition, not necessarily mainstream. It is left to the discretion, and it is the
sole responsibility of the user of the information indicated in the presentation, to determine
if procedures and recommendations described are appropriate for a patient. Neither the
authors nor the sponsors (such as Apex Energetics) of this information can be held
responsible for the information or any inadvertent errors or omissions of the information.
The information in this presentation should not be construed as a claim or representation
that any procedure or product mentioned constitutes a specific cure, palliative
or ameliorative. Procedures and products described should be considered as adjunctive
to other accepted conventional procedures deemed necessary by the attending
licensed doctor.
It is the concern of the Department of Health and Human Services that no homeopathic
and nutritional supplements be used to replace established, conventional medical
approaches, especially in cases of emergencies, serious or life threatening diseases
or conditions.
We share in this concern, as replacing conventional treatment with such remedies,
especially in serious cases, may deprive the patient of necessary treatment and
thereby cause harm as well as potentially pose a major legal liability for the health
professional involved. Apex formulas should not be used as replacements for
conventional medical treatment.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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4. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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6. Healthy and Unhealthy Neurons
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7. How Old is Your Brain?
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8. Atrophy of the Memory Centers
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10. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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11. Questions to Ask
• Is it too late?
• Is it permanent?
• What changes can be made?
• Will it get worse?
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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12. What are the
Earliest Signs of
an Aging Brain?
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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13. Earliest Signs of an Aging Brain
• Fatigue promoted by brain activity – driving,
reading, brain tasks
• Depression – lack of healthy brain firing leads
to depression
• Poor Digestive Function – 90% of the brain’s
output goes to the pontomedullary system
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14. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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15. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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16. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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17. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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18. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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20. Moderate Signs of Aging Brain
• Inability to focus or concentrate
• Difficulty learning new tasks
• Chronic constipation, opportunistic intestinal
overgrowth, digestive enzyme insufficiency
• Increased sympathetic tone leading to:
– Increased blood pressure
– Increased resting heart rate
– Stress susceptibility
– Poor blood flow
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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21. Significant Brain Aging
• Inability to work professionally
• Inability to appreciate life
• Inability to perceive neurological loss
• Early signs of neurological disease
– tremors
– inability to find directions
– etc.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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22. Severe Brain Aging
• Neurodegenerative disease
• Uncontrolled bladder tone
• Bowel obstruction and inability to digest food
• Inability to taste, smell, or develop social
relationships
• Dependency on family and medical staff for
daily functions
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24. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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25. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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26. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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27. What are the Mechanisms
for Poor Brain Aging?
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28. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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29. Brain Aging of the
Memory System
Dementia and Alzheimer’s Disease
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30. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
Memory and the aging brain.
• Studies that look at only the healthiest
elderly tend to find minimal cognitive decline
even into the ninth decade.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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31. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
Memory and the aging brain.
• It is clear that significant cognitive decline is
not an inevitable consequence of advanced
age.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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32. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
Memory and the aging brain.
• More than 4 million Americans have
dementia, and the number is projected to
grow to 14 million in the next 50 years.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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33. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
Memory and the aging brain.
• Currently there is no cure for dementia.
• All people are at risk for dementia, with the
greatest risk factor being increased age.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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34. • Are you getting older?
• Do you have the earliest
signs of dementia?
• Are you taking this seriously?
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35. Earliest Signs of Dementia
• Poor short-term memory
• Difficulty learning
• Difficulty with directions
• Decreased brain endurance
If you have the symptoms, when did they
start and how fast are they going?
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36. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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37. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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47. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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49. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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51. Brain Affected Areas
in Alzheimer’s Disease
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52. Symptoms of Cholinergic
Pathways Degeneration
• Loss of photographic memory
• Difficulty with sense of directions
• Poor memory
• Memory lapses
• Poor verbal memory
• Slow mental speed
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53. Signs of Cholinergic
Pathways Degeneration
• Constantly losing keys, phone, etc.
• Constantly forget where car is parked
• Dependency on navigations system for
directions
• Must write everything down
• Constantly forgetting appointments,
tasks, etc.
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54. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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55. ACETYL-CH® ACTIVE (K40)
• Huperzine A
• Alpha-GPC
• N-Acetyl L-Carnitine
• Pantothenic Acid
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56. Brain Aging of the
GABAergic System
Anxiety, Restlessness, Panic Attacks
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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58. Symptoms of GABAergic
Pathway Degeneration
• Feelings of anxiety or panic for reasons
• Difficulty shutting mind off
• Feelings of being overwhelmed for no reason
• Disorganized attention
• Feelings of restlessness
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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59. Signs of GABAergic
Pathway Degeneration
• Anxiety episodes
• Cannot initiate projects due to constant
distractions
• Startled easily and difficulty calming down
afterwards
• Severely sensitive to light and sound
• Increased resting heart rate
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60. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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61. GABATONE® ACTIVE (K39)
• Valerian Root extract
• Lithium Orotate
• Passion Flower extract
• L-Theanine
• L-Taurine
• Pyridoxal-5-Phosphate
• Manganese Succinate
• Zinc Glycinate
• Magnesium Succinate
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62. Brain Aging of the
Serotonergic System
Depression, Loss of Joy, Poor Focus,
Sense of Self and Purpose
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64. Symptoms of Serotonergic
Pathway Degeneration
• Guilty depression
• Inability to feel joy from hobbies, friends,
music, food, etc.
• Depressed with overcast weather or chronic
lack of sunlight
• Loss of interest in life
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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65. Signs of Serotonergic
Pathway Degeneration
• Social isolation with unwillingness to go out
• Depression
• Cravings and overeating of carbohydrates
and sugars
• Slowed reflexes and coordination
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66. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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67. SEROTONE® ACTIVE (K38)
• 5-Hydroxytryptophan
• St. John’s Wort
• SAMe
• Pyridoxal 5 Phosphate
• Niacinamide
• Magnesium Citrate
• Methylcobalamin
• Calcium Folinate
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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68. Brain Aging of the
Dopaminergic System
Depression, Loss of Motivation,
Inability to Finish Tasks,
Slow Movements, Slow Mind
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70. Dopamine Receptors in the Brain
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71. Areas of the Brain in Depression
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72. Symptoms of Dopaminergic
Pathway Degeneration
• Feelings of hopelessness and worthlessness
• Inability to handle stress
• Unable to self-motivate to start or finish
tasks
• Need to consume caffeine to stay focused
• Depression
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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73. Signs of Dopaminergic
Pathway Degeneration
• Depression
• Isolation
• Quick to snap at every little thing
• Poor compliance with healthcare, exercise, etc.
• Anger episodes
• Hypokinesia (slow and diminished movements)
• Constipation with diminished smell or taste
perception
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74. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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75. DOPATONE® ACTIVE (K41)
• Mucuna Pruriens
• Beta-Phenylethylamine
• Blueberry extract
• D,L – Phenylalanine
• N-Acetyl L-Tyrosine
• Pyridoxal 5 Phosphate
• Alpha Lipoic Acid
• Selenium
• N-Acetyl L-Cysteine
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76. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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77. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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78. Phosopholipid Integrity
60% of the Brain is Made Up
of Phosopholipids
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79. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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80. Phosopholipids and Neuron
Structure
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81. Neuroscience. 1999;94(1):305-14.
Age-related changes in synaptic function:
analysis of the role of dietary supplementation.
• DHA is used to enhance cell fluidity, neuronal
signaling, neuronal dendrite growth, and
brain function, as well as reduce
inflammation, and decrease the incidence of
neurodegenerative conditions.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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82. Int. J Neurosci. 1996 Nove;87(3-4):141-9.
Essential fatty acids preparation (SR-3) improves
Alzheimer’s patient’s quality of life.
• DHA intake has demonstrated the ability to
boost brain function, improve quality of life,
and reduce the incidence of
neurodegenerative conditions.
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83. Current Enzyme Inhibition. 2005;1:11-20.
Sesamin and sesamolin: nature’s therapeutic lignans.
• Sesamin and Sesamolin found in sesame seed
oil and have exhibited properties to protect
neurons and modulate microglia
neuroinflammatory properties.
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84. Int J of Biomed Sci. 2006:2:284-288.
Neuroprotective effects of sesamin and sesamolin
on gerbil brain in cerebral ischemia.
• Sesamin and sesamolin have the ability to
attenuate excess generation of oxidative
stress stimulated by microglia and to
reduce infarct size by approximately 50%
when compared with the control group in
a cerebral artery occlusion study.
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85. Biochem J. 1982;208(3):631-40.
Influence of dietary fat on lipid composition
of rat brain synaptosomal and microsomal membranes.
• Phosphatidylcholine (PC) plays a crucial role
in the formation and structural integrity of
neurons and brain architecture.
• PC supports cell-membrane integrity,
fluidizing the membranes, and it supports
intracellular communication.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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86. Artif Cells Blood Substit Immobil Biotechnol. 1994;22(1):83-9.
Effects of lecithin-emulsified perflurochemical
compounds in ischemic brain injury.
• Dietary supplementation with
Phosphatidylcholine has exhibited
protection against oxidative and ischemic
neuronal damage.
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87. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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88. BRAIN-E® DHA (K53/55/65)
PHYTO BRAIN-E® (K54)
• DHA
• EPA
• Phosphatidylcholine
• Sesame oil
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89. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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90. Phosopholipids and Neuron
Structure
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91. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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92. Mitochondria
Oxidative
Phosphorylation
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93. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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94. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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95. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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96. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
Mitochondrial decay in the brains of old rats:
ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.
• To investigate the mitochondrial decay and
oxidative damage resulting from aging, the
kinetics of the mitochondrial complexes
were examined in the brains of young and
old rats as well as in old rats fed alpha-
lipoic acid plus acetyl-L-carnitine.
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97. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
Mitochondrial decay in the brains of old rats:
ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.
• The brain mitochondria of old rats, compared
with young rats, had significantly decreased
endogenous antioxidants and superoxide
dismutase activity; more oxidative damage to
lipids and proteins; and decreased activities
of complex I, IV, and V.
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98. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
Mitochondrial decay in the brains of old rats:
ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.
• Feeding LA/ALC to old rats partially restored
age-associated mitochondrial dysfunction to
the levels of the young rats.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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99. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
Mitochondrial decay in the brains of old rats:
ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.
• These results indicate that oxidative
mitochondrial decay plays an important
role in brain aging and that a combination
of nutrients targeting mitochondria could
ameliorate mitochondrial decay.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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100. J Neurosci Res. 2008 Aug 1;86(10):2339-52.
Age-related decreases in NAD(P)H and glutathione
cause redox declines before ATP loss during glutamate
treatment of hippocampal neurons.
• We conclude that old-aged neurons consume
more NADH and glutathione, leading to a
catastrophic decline in redox ratio, leading to
age-related glutamate excitotoxicity.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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101. Brain Res. 2006 May 23;1090(1):35-44. Epub 2006 May 2.
Age-related changes in glutathione and glutathione-related
enzymes in rat brain.
• The most reliable and robust risk factor for
some neurodegenerative diseases is aging.
• It has been proposed that processes of aging
are associated with the generation of
reactive oxygen species and a disturbance of
glutathione homeostasis in the brain.
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102. Brain Res. 2006 May 23;1090(1):35-44. Epub 2006 May 2.
Age-related changes in glutathione and glutathione-related
enzymes in rat brain.
• The results suggested a significant age-
related reduction of reduced glutathione
(GSH) level in all brain regions examined,
associated with an increase of GSH oxidation
to glutathione disulfide (GSSG) and decrease
of the GSH/GSSG ratio.
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103. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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104. GLUTATHIONE RECYCLER® (K57)
• Cordyceps extract
• Gotu Kola extract
• Milk Thistle extract
• N-Acetyl Cysteine
• Alpha Lipoic Acid
• L-Glutamine
• Selenium
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105. N-Acetyl Cysteine
(Research Review)
• Research has clearly demonstrated that
N-Acetyl Cysteine is rapidly metabolized to
intracellular glutathione.
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106. Alpha Lipoic Acid
(Research Review)
• It directly recycles and extends the
metabolic life spans of vitamin C,
glutathione, and coenzyme Q10, and it
indirectly renews vitamin E, all of which are
necessary for glutathione recycling.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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107. L-Glutamine
(Research Review)
• Research has demonstrated that glutamine
is important for the generation of
glutathione.
• It is transported into the cell, converted to
glutamate, and readily available for
intracellular glutathione synthesis.
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108. Selenium
(Research Review)
• Selenium is a trace element nutrient that
serves as the essential cofactor for the
enzyme glutathione peroxidase.
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109. Cordyceps
(Research Review)
• It has been shown to activate glutathione
peroxidase synthesis in the body.
• Cordyceps research has demonstrated that
it helps protect cells by engaging the
glutathione enzyme cycle.
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110. Gotu Kola
(Research Review)
• Research has clearly demonstrated that
oral intake very rapidly and dramatically
increases the activity and amount of
glutathione perioxidase and the quantity
of glutathione.
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111. Milk Thistle
(Research Review)
• Administration of milk thistle has shown
to significantly increase glutathione,
increase superoxide dismutase activity,
and have a positive influence in the ratios
of reduced and oxidized glutathione.
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112. NEURO-PTX® (K47)
• N-Acetyl Cysteine
• N-Acetyl Carnitine
• Alpha Lipoic Acid
• Creatine Monohydrate
• Genistein
• Milk Thistle extract
• CoQ10
• Alpha Ketoglutarate
• d-alpha tocopherol succinate
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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113. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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114. Microglia
Neuroinflammation
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115. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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118. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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119. NEUROFLAM™ (K46)
• Apigenin
• Luteolin
• Baicalin
• Rutin
• Catechin
• Curcumin (turmeric)
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120. Mol Nutr Food Res. 2008;52(4):427-38.
Plant-derived polypheonls attenuate lipopolysaccharide-induced
nitric oxide and tumour necrosis factor production
in murine microglia and macrophages.
• Apigenin attenuated lipopolysaccharide
induced nitric oxide and TNF production in
microglia.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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121. J Neuroinflammation. 2008;25(5):41.
Apignin and luteolin modulate microglial activation via
inhibition of STAT-1 induced CD40 expression.
• Apigenin and luteolin concentration-
dependently suppressed IFN-gamma-
induced CD40 expression of microglia.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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122. J Neuroinflammation. 2008;25(5):41.
Apignin and luteolin modulate microglial activation via
inhibition of STAT-1 induced CD40 expression.
• Our findings provide further support that
apigenin and luteolin's anti-inflammatory
effects have neuroprotective properties in
various neurodegenerative disorders.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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123. Neurosci Lett. 2008;448(2):175-179.
Luteolin protects dopaminergic neurons from inflammation-induced
injury through inhibition of microglial activation.
• Luteolin also significantly inhibited LPS-
induced activation of microglia.
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124. Neurosci Lett. 2008;448(2):175-179.
Luteolin protects dopaminergic neurons from inflammation-induced
injury through inhibition of microglial activation.
• Our results demonstrate that luteolin may
protect neurons by inhibiting microglia
activation.
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125. Proc Natl Acad Sci USA. 2008;105(21):7534-7539.
Luteolin reduces IL-6 production in microglia by inhibiting
JNK phosphorylation and activation of AP-1.
• Luteolin may be useful for mitigating
microglia neuroinflammation.
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126. J Pharmacol Exp Ther. 2003;305(2):638-45.
Flavonoid baicalein attenuates activation-induced
cell death of brain microglia.
• Our current results suggest that baicalein
selectively inhibits activated microglia.
• Also, inhibiting effects of baicalein were
specific for the inflammatory stimulus that
activated microglia.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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127. Neurosci Lett. 2008;441(1):16-20.
Neuroprotective effect of baicalein against MPTP neurotoxicity:
behavioral, biochemical and immunohistochemical profile.
• The results suggest that baicalein possesses
potent neuroprotective activity and has
potential anti-Parkinson’s activity.
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128. Neuroreport. 2001;12(10):2199-202.
Baicalein protects cortical neurons from beta-amyloid
(25-350 induced toxicity).
• Baicalein protects lipoxygenase mediated
pathways for micoroglia activated
neuroinflammation associated with
Alzheimer’s disease.
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129. Invest Opthalmol Vis Sci. 2008; Nov 14.
Baicalein reduces inflammatory process
in a rodent model of diabetic retinopathy.
• Baicalein has demonstrated to ameliorate
inflammatory processes of diabetic
retinopathy and has inhibitory activity
against neuron loss in diabetic retinas.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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130. Brain Res. 2008; Oct 18 [Epub ahead of print].
Baicalein protects rat brain mitochondria against
chronic cerebral hypoperfusion-induced oxidative damage.
• Baicalein has been found to protect neuronal
mitochondria damage and swelling promoted
by chronic cerebral hypoperfusion and has
been suggested as a potential support agent
for dementia caused by decreased blood flow
to the brain.
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131. Neurochem Res. 2008;33(10):2044-53.
Curcumin protects dopaminergic neuron against LPS induced
neurotoxicity in primary rat neuron/glia culture.
• Curcumin has demonstrated the ability to
protect dopaminergic neurons against
lioppolysaccharide induced neurotoxicity in
animal neurona/glia culture.
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132. Acta Pharmacol Sin. 2007;28(10):1645-51.
Curcumin attenuates the release of pro-inflammatory cytokines
in lipopolysaccharide-stimulated BV2 microglia.
• Curcumin has been found to have
neuroprotective effects by blocking the
production of pro-inflammatory and
cytotoxic mediators by activated microglia.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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133. REPAIRVITE® (K60)
• L-Glutamine
• MSM
• Licorice extract
• Aloe Vera extract
• Marshmallow extract
• Slippery Elm extract
• Spanish Moss
• German Chamomile extract
• Marigold extract
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134. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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136. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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137. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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138. Blood Flow = Function
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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139. BMC Neurosci. 2010 Jun 24;11(1):78.
Study of the nitric oxide system in the rat cerebellum during aging.
• In the senescent cerebellum, inducible nitric
oxide system activity results in an increase of
the protein nitration.
• These changes might be related to the
oxidative damage detected with aging in the
cerebellum.
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140. Brain Res. 2002 Nov 29;956(2):385-92.
Age-related changes of the nitric oxide system in the rat brain.
• Concerning age, in the cerebellum the eNOS
expression decreased whereas iNOS
increased.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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141. Biochim Biophys Acta. 1999 May 5;1411(2-3):415-36.
Roles of nitric oxide in brain hypoxia-ischemia.
• A large body of evidence has appeared over
the last 6 years suggesting that nitric oxide
biosynthesis is a key factor in the
pathophysiological response of the brain to
hypoxia-ischemia.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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142. Biochim Biophys Acta. 1999 May 5;1411(2-3):415-36.
Roles of nitric oxide in brain hypoxia-ischemia.
• In conclusion, it appears that activation of
iNOS mediates ischemic brain damage.
• However, there is a simultaneous
compensatory response through eNOS
activation within the endothelium of blood
vessels, which mediates vasodilation and
hence increases blood flow to the damaged
brain area.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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143. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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144. NITRIC BALANCE® (K62)
• ATP
• Huperzine A
• Vinpocetine
• Alpha-GPC
• Alpha-Ketoglutaric Acid (AKG)
• Xanthinol Nicotinate
• Acetyl L-Carnitine
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145. NITRIC BALANCE® (K62)
• Provides compounds that are used to
support the expression of eNOS and nNOS,
while dampening the expression of iNOS.
Healthy balance of NO helps the body to:
1. Support tissue healing
2. Dampen tissue inflammation
and destruction
3. Modulate autoimmune reactions
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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146. Adenosine
(Research Review)
• Adenosine increases extracellular ATP,
which has been found to activate eNOS
and nNOS.
• More importantly, it does not activate
iNOS activity, and has even
demonstrated suppressive iNOS activity.
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147. Huperzine A
(Research Review)
• Huperzine A is powerful compound for
ideal nitric oxide isomer expression
because it enhances acetylcholine
activity necessary for eNOS and nNOS,
and it has powerful iNOS inhibiting
properties.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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148. Huperzine A
(Research Review)
• Huperzine is a potent natural
acetylcholine esterase inhibitor leading
to increased acetylcholine activity that is
necessary for ideal eNOS and nNOS
activity.
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149. Huperzine A
(Research Review)
• Not only does Huperzine A inhibit iNOS
activity directly, but it also suppresses
the same cytokines that stimulate iNOS.
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150. Vinpocetine
(Research Review)
• Vinpocetine is classified as selective
cyclic GMP phosphodiesterase (PDE)
inhibitor and modulates vascular tone
and nitric oxide release in system
circulation.
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151. Vinpocetine
(Research Review)
• The net effect of PDE inhibitors, such as
vinpocetine, is to increase eNOS activity
leading to vasodilation and increase
blood delivery to peripheral tissues for
recovery.
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152. Vinpocetine
(Research Review)
• In addition to vinpocetine’s properties of
eNOS activation, the compound has
powerful influences on the
neurotransmitter acetylcholine.
• Acetylcholine activity is critical for ideal
eNOS receptor site activity.
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153. Alpha-GPC
(Research Review)
• Oral intake of Alpha GPC has been shown
to increase acetylcholine levels in the
body.
• Acetylcholine activity promotes nitric
oxide synthase activity and nitric oxide
promotes acetylcholine activity that is
responsible for eNOS vascular dilation
and nNOS synaptic activity.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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154. Alpha-Ketoglutaric Acid (AKG)
(Research Review)
Alpha-Ketoglutaric Acid is a citric cycle
intermediate and can be used to help
produce nitric oxide via the urea cycle
and metabolize harmful nitrogen out of
the body.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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155. Alpha-Ketoglutaric Acid (AKG)
(Research Review)
• AKG supplementation has been shown to
have positive modulating activity on iNOS.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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156. Alpha-Ketoglutaric Acid (AKG)
(Research Review)
• AKG supplementation has been shown to
help modulate nitrogen balance and
preserve protein synthesis after cell injury.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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157. Xanthinol Nicotinate
(Research Review)
It has demonstrated properties to
increase eNOS by its nicotinate
component activity on the acetylcholine
receptors.
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158. Xanthinol Nicotinate
(Research Review)
• Clinical research has found that xanthinol
nicotinate has antioxidant properties that
may lead to decreased iNOS activities.
• Several research studies have found it
improves microcirculation and aids in
healing.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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159. Acetyl L-Carnitine (LAC)
(Research Review)
• Research has shown that LAC mimics
acetylcholine activity, and has shown
effectiveness in acetylcholine-mediated
pathways.
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160. Acetyl L-Carnitine (LAC)
(Research Review)
• Acetylcholine activity promotes nitric
oxide synthase activity, and nitric oxide
promotes acetycholine activity that is
responsible for eNOS vascular dilation
and nNOS synaptic activity.
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161. NEURO2™ (K45)
• Ginkgo Biloba
• Vinpocetine
• Butcher’s Broom
• Feverfew
• Cayenne (Capsaicin)
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162. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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163. Altered Methylation
and Neurodegenerative
Disease
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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164. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
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165. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
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166. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
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167. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
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168. Heijer, T, et al. 2002;1:170-175.
Homocysteine and brain atrophy on MRI of non-demented elderly.
• A study of 1077, non-demented people
investigated the association between plasma
homocysteine levels and severity of
hippocampal, amygdalar, and global brain
atrophy on MRI.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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169. Heijer, T, et al. 2002;1:170-175.
Homocysteine and brain atrophy on MRI of non-demented elderly.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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170. Heijer, T, et al. 2002;1:170-175.
Homocysteine and brain atrophy on MRI of non-demented elderly.
• The results concluded higher plasma
homocysteine levels are associated with
more atrophy of the hippocampus and
cortical regions in elderly at risk or
Alzheimer’s disease.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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171. Heijer, T, et al. 2002;1:170-175.
Homocysteine and brain atrophy on MRI of non-demented elderly.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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172. A study published in Neurology called the
Rotterdam Scan Study with over 1,000 study
subjects, demonstrated that homocysteine
elevations were associated with silent brain
infarcts and white matter lesions.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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173. METHYL-SP™ (K14)
• Folate 1200 mcg (300%)
• B-12 600 mcg (10,000 %)
• Choline 50 mg
• Trimethlyglycine 550 mg
• MSM 50 mg
• Beet (Root) 50 mg
• Betaine HCl 60 mg
• Magnesium 140 mg (35%)
• Vitamin C 50 mg (83%)
• Vitamin B6 10 mg (500%)
• Vitamin E 20 IU (66%)
• Riboflavin 10 mg (588%)
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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174. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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175. Autoimmunity
in the Aging Brain
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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176. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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177. Neuroreport. 1995 Jun 19;6(9):1274-6.
Immune aging and Alzheimer’s disease.
• The model thus emerging for sporadic
Alzheimer's disease is that of a T-cell-
mediated chronic autoimmune syndrome
following the age-dependent loss of thymic
function.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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178. Gerontology. 1997;43(1-2):79-94.
Neuroautoimmunity: pathogenic implications
for Alzheimer’s disease.
• Immune factors such as cellular immunity,
autoimmunity, and inflammation may play
a pathogenic role in Alzheimer's disease
(AD), a neurodegenerative disorder.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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179. Clin Rev Allergy Immunol. 2011 Jan 14.
Autoimmunity and autoantibodies in Parkinson’s disease.
• Recent revelations of immune alterations in
Parkinson's disease have led to the convergence
that an autoimmune mechanism may play a role.
• The presence of seven autoantibodies
previously found to be associated with central
nervous system manifestations, namely:
antineuronal-cells, anti-brain lysate, anti-dsDNA,
anti-phosphatidylserine, anti-cardiolipin, anti-
serotonin, and anti-melanocytes antibodies.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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180. Clin Rev Allergy Immunol. 2011 Jan 14.
Autoimmunity and autoantibodies in Parkinson’s disease.
• Clinical manifestations of Parkinson's
disease, particularly dyskinesia and
depression, were found to be associated
with the presence of these autoantibodies.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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181. J Affect Disord. 2009 Aug;116(3):192-200.
Anti-brain antibodies in adult patients
with obsessive-compulsive disorder.
• An autoimmune hypothesis has been
suggested for a subtype of Obsessive-
Compulsive Disorder (OCD) with childhood
onset.
• For a proportion of OCD patients,
autoimmune reactions towards neuronal
structures are present.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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182. Cyrex™ Labs
Array 5 - Neuroautoimmunity Panel
Coming Soon
www.CyrexLabs.com
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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183. Putting It All Together
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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184. What State is the Neuron In?
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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185. What State is the Microglia In?
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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186. Earliest Signs of an Aging Brain
• Fatigue promoted by brain activity – driving,
reading, brain tasks
• Depression – lack of healthy brain firing
leads to depression
• Poor Digestive Function – 90% of the brain’s
output goes to the pontomedullary system
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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187. Moderate Signs of an Aging Brain
• Inability to focus or concentrate
• Difficulty learning new tasks
• Chronic constipation, opportunistic intestinal
overgrowth, digestive enzyme insufficiency
• Increased sympathetic tone leading to:
– increased blood pressure
– increased resting heart rate
– stress susceptibility
– poor blood flow
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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188. Significant Brain Aging
• Inability to work professionally
• Inability to appreciate life
• Inability to perceive neurological loss
• Early signs of neurological disease
– tremors
– inability to find directions
– etc.
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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189. Severe Brain Aging
• Neurodegenerative disease
• Uncontrolled bladder tone
• Bowel obstruction and inability to digest food
• Inability to taste, smell, or develop social
relationships
• Dependency on family and medical staff for
daily functions
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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190. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
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191. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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192. Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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193. IMPORTANT & RELEVANT
WEEKEND SEMINARS
DEVELOPED BY
DATIS KHARRAZIAN,
DC, DHSc, MS, MNeuroSci, FACFN, FABVR, FAACP,
DACNB, DABCN, DIBAK, CNS
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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194. FUNCTIONAL BLOOD CHEMISTRY
CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS.
THIS WEEKEND COURSE IS DESIGNED TO HELP YOU:
• Understand the differences between functional and pathological ranges on
Lab Reports.
• Understand the key principles of laboratory biochemistry.
• Understand how to differentially evaluate blood chemistry patterns
for nutritional purposes.
• Identify nutritional and herbal compounds that can be used to
support nutritional imbalances through a review of medical literature.
RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS
WEEKEND COURSE:
• CARDIO GI & IMMUNE AXIS (2-HOUR SEMINAR CD ALSO AVAILABLE WITH NOTES).
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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195. MASTERING THE THYROID
CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS.
This course will redefine and create the new standard for natural medicine support of thyroid
imbalances. Dr. Kharrazian has meticulously organized a comprehensive and detailed three-day
course to help clinicians master the concepts of thyroid physiology, assessment, and clinical
applications.
The following tools and concepts will give you insight into this unique approach:
• Thyroid-Immune-Nervous System-Endocrine crosstalk and its clinical implications
• The impact of thyroid hormones on every major physiological process
• A step-by-step approach to conducting a thyroid physical examination
• A complete review of the literature on natural supplements that supports or disrupts thyroid function
• Identify 24 common and newly highlighted patterns that lead to thyroid imbalances on lab tests
RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS WEEKEND COURSE:
• THYROID-BRAIN-IMMUNE PHYSIOLOGICAL CROSSTALK
• AUTOIMMUNE THYROID RESEARCH AND PRACTICE UPDATES (2-HOUR SEMINAR OR CD ALSO
AVAILABLE WITH NOTES)
• THYROID PRINCIPLES AND CASE STUDIES (2-HOUR SEMINAR OR CD ALSO AVAILABLE
WITH NOTES)
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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196. NEUROTRANSMITTERS & BRAIN
CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS.
Dr. Kharrazian reviews physiological interactions among neurotransmitters,
hormones, and the immune system. Clinical applications regarding questionnaire
forms, laboratory tests, and nutritional supplements will be emphasized
in the course.
A complete review of the literature that pertains to natural supplements
that support neurotransmitters, hormones, and the immune system will be provided
in the course book. Numerous clinical pearls and case studies will be presented to
provide information that can be used effectively by the practicing clinician.
TAKE YOUR PRACTICE AND CLIENTS’ HEALTH TO THE NEXT LEVEL WITH
THIS COURSE!
RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS
WEEKEND COURSE:
• INTRODUCTION TO NEUROCHEMISTRY (2-HOUR SEMINAR)
• FUNCTIONAL BLOOD CHEMISTRY & FUNCTIONAL ENDOCRINOLOGY
(CEU-APPROVED WEEKEND COURSES)
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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197. For dates and additional information:
PLEASE LOOK FOR OUR
WEEKEND & 2-HOUR COURSE
SCHEDULE!
www.apexseminars.com
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
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