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Stress and the Autonomic Nervous System

©2012 True Health Medical Center

Anju Usman, M.D. True Health Medical Center.

Page # 1


Au4sm ONE Lombard, Illinois

May 2012

Anju Usman, MD True Health Medical Center

Disclaimer

•  Informa4on is for educa4onal purposes only •  Not to be taken as specific medical advice •  All medical decisions regarding your child’s health issues should be discussed with your health care provider

•  Clinical trials have not been done on treatment approaches discussed

Sometimes the most important thing in a whole day is the rest we take between two deep breaths. Etty Hillesum

Biomedical Stressors Gene4c predisposi4ons

Mother’s Burden Toxic Metals

Environmental Pollutants Electromagne4c Fields

Sensory Input Stress/Internal Conflicts

Dietary Factors Allergens

Microbial/Biofilm Immune/Inflammatory Burden

Stressed Out Lives!

– Biomedical – Physical – Mental – Emo4onal – Social

Nega4ve Ways of Handling Stress •  Watching television •  Skipping exercise •  Junk food, Fast food •  SUGAR •  CAFFEINE •  Pharmaceu4cals •  Alcohol •  Cell Phones, Emails, Tex4ng, Internet •  Anger, Yelling, Blaming Others… •  Loss of self confidence and self esteem




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Stress Can Age You •  University of California, San Francisco, looked at white blood cells in mothers whose children suffered from chronic disorders like au4sm.

•  They found clear signs of accelerated aging in mothers who had cared the longest for children with disabili4es.

•  The youngest cells boast the longest telomeres. •  But telomeres in the more stressed-‐out moms were significantly shorter.

•  Reflects an accelerated aging pa]ern from 7-‐15 yrs.

Stressed Out Babies In Utero - work, marriage, vaccines, diet, ultrasound, meds… Delivery Premies Infancy

•  Metabolic Toxins – metals, chemicals Allergens Dietary Infections EMFs Pharmaceutical Agents

•  Psychosocial Sensory overload Constant demands Separation

“Stress in infancy can affect genetics for generations to come”

How do children manifest stress? – Colic – Sleep disrup4on – Sensory issues -‐ texture, sound, lights – Flight or fight response (running or aggression)

– Tantrums/Meltdowns – Isola4on/disengaged – Need for sameness

What are the main metabolic manifesta4ons of chronic stress?

•  Nervous System Maladap4on •  Endocrine /Hormone Imbalance •  Immune/Inflammatory Dysregula4on •  Gastrointes4nal Disorders •  Mitochondrial Dysfunc4on •  Oxida4ve Stress

Nervous System

•  Autonomic Nervous System – Sympathe4c – Parasympathe4c

•  Neuroendocrine System – Hypothalamus/Pituitary Axis

•  Limbic System – Emo4onal Nervous System

The Emo4onal Nervous System The Limbic System

Emotions Memories Aggression OCD Pleasure/Pain Focus/Attention

Pituitary Hypothalamus Amygdala Hippocampus Cingulate Gyrus Basal Ganglia Ventral Tegmental Prefrontal Cortex




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Cor4sol Levels During Human Aging Predict Hippocampal Atrophy and Memory Deficits

Lupien, Sonia. Nature Neuroscience 1998

•  Elevated glucocor4coid levels produce hippocampal dysfunc4on and correlate with individual deficits in spa4al learning in aged rats.

•  Humans with significant prolonged cor4sol eleva4ons showed reduced hippocampal volume and deficits in hippocampus-‐dependent memory.

•  The degree of hippocampal atrophy correlated strongly with both the degree of cor4sol eleva4on over 4me and current basal cor4sol levels.

•  Therefore, basal cor4sol eleva4on may cause hippocampal damage and impair hippocampus-‐dependent learning and memory in humans.

Abbreviated schematic of the Welch-Ruggiero unified brain/gut theory of emotions. The structures shown are sites of action of transmitters and peptides in mediating neurohumoral mechanisms sustaining adaptive behaviors accompanying arousal. Shaded area indicates viscera and brain are one system with bi-directional communication between the two, a theory that is in line with James-Lange.

PREDICTED ROLE OF SECRETIN AND OXYTOCIN IN THE TREATMENT OF BEHAVIORAL AND DEVELOPMENTAL DISORDERS: IMPLICATIONS FOR AUTISM Martha G. Welch and David A. Ruggiero

– Hypotheses •  Inflamma4on is encoded by the brain •  Inflamma4on(stress) causes the individual to maladapt

– Assump4ons •  The brain and gut form a single physiologic circuit •  The gut-‐brain axis is the crossroads of condi4oning via interac4on with mother

•  The gut is cri4cal to condi4oning reac4ons to stress in the early post natal period

– Treatment • Pep4des like Secre4n and Oxytocin can help a dysregulated gut-‐brain system

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Dr. Martha Welch 2009 Combined Administra4on of Secre4n and Oxytocin Inhibits Chronic Coli4s and Associated Ac4va4on of Forebrain Neurons

–  Journal of Neurogastroenterology and Mo4lity 2010 •  Secre4n expression in the colon is lower than in the intes4nes

•  S/OT decreased TNF alpha and IFN gamma in the colon •  S/OT combo reduced inflamma4on •  S/OT decreased ulcers •  S/OT decreased IL-‐6 in amygdala •  S/OT may act in synchrony

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Secre4n Oxytocin •  Gut mo4lity •  Alkaliniza4on •  Co-‐localize with serotonin •  Improves bile flow •  Increases blood flow to GI •  Brain affects NE, Dopamine, Angiotensin II, AT(1)R

•  Released by Hypothalamus

•  Gut mo4lity •  Inhibits gastric acid •  Vasodila4on •  Co-‐localize with CCK

•  Brain antagonists to CRH

•  Released by Amygdala

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Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants Laura Hewitson Acta Neurobiol Exp 2010 •  Vaccinated animals showed an increase in total brain volume. •  The amygdala, a specific part of the brain associated with

emo4onal responses did not show abnormali4es un4l aier the 12-‐month vaccines had been given.

•  In addi4on, aier the 12-‐month vaccines only, the func4onal brain scans showed significant differences between vaccinated and unvaccinated groups.

•  Vaccine administra4on was associated with an increase in opioid binding ac4vity in the amygdala compared with a decrease in the unvaccinated group.




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Au4sm, amnesia, hippocampus and learning DeLong GR Neurosci Biobehav Rev. 1992

“Au4sm is postulated to be the developmental syndrome of hippocampal dysfunc4on. The hippocampus is postulated to be necessary for normal development in the child of language syntax, seman4cs, and pragma4cs; the capacity for crea4vity and genera4vity in language and behavior, and combinatorial possibili4es in general; for the integra4on of mo4va4onal states with

experience and learning; and for the construc4on of a complex, useful and flexible structure of meaning.”

HPA Axis and the Nervous System : The Neuroendocrine System

•  Controls reac4ons to stress and regulates many processes, including diges4on, immunity, mood and emo4ons, sexuality, and energy storage and use. –  Hypothalamus -‐ homeostasis of the body –  Pituitary -‐ master gland of the endocrine system –  Adrenal Gland -‐ interfaces with Hypothalamus

•  Neurobiology of mood disorders and func4onal illnesses, including anxiety, insomnia, PTSD, ADHD, chronic fa4gue syndrome, fibromyalgia and IBS.

•  Both hormones and neurotransmi]ers are chemical messengers. They just travel thru different pathways.

50% of 30 kids with ADD showed an abnormal HPA response. As measured by an abnormal dexamethasone suppression test (DST) and abnormal diurnal rhythm.

Normal Diurnal Cor4sol Pa]ern

Abnormal Diurnal Cor4sol Pa]ern HPA Axis

Hypothalmus Pituitary Adrenal Thyroid Gonad




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Adrenal Hormones Adrenal Cortex

Steroid Hormones • Cortisol

(glucocorticoid) • Aldosterone

(mineralocorticoid) • Progesterone • DHEA • Testosterone • Estrogen

Adrenal Medulla Catecholamines

• Epinephrine • Norepinephrine

Adrenal Pathways

Smith Lemli Opitz Syndrome and Low Cholesterol

•  Benefits of cholesterol feeding in SLOS Kelley RT. Inborn errors of cholesterol biosynthesis. Adv Pediatric 2000;47

–  Beginning to walk –  Star4ng to run –  Growth improvement –  Less infec4ons –  Less UV light sensi4vity –  Increased alertness –  Head banging stops –  Decreased tac4le defensiveness –  Increased sociability –  Behavior improves –  Talking started in adults

Tierney 2006

Adrenal Response to Stress

Adapta4on – 3 stages

• Alarm (increased cor4sol, normal DHEA, increased epinephrine, norepinephrine)

• Resistance (pregnenolone steals cholesterol to make cor4sol, but at the expense of sex hormones, increased cor4sol, low DHEA)

• Exhaus4on (low cor4sol, low DHEA)

Hans Selye, M.D

Impact of Adrenal Stress Syndrome

Blood Sugar Imbalances – High cor4sol, insulin receptor insensi4vity, excess insulin produc4on. Insulin resistance and hyperglycemia.

– Low cor4sol affects liver’s ability for gluconeogenesis and glycogenolysis, causing hypoglycemia.


Sleep – Adrenal hypofunc4on, low cor4sol, loss of ability to maintain blood sugar levels at night, causes stress response.

– The stress response causes the medulla to secrete epinephrine and norepinephrine to try to mobilize glucose to compensate for a lack of cor4sol.

– Epinephrine and Norepinephrine ac4vate the sympathe4c nervous system and cause night 4me awakening.

Strakis. Neuroendocrinology and pathophysiology of the stress response. 1995




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Thyroid Defects – High cor4sol has a suppressive effect on 5’deiodinase which converts T4 (inac4ve) to T3(ac4ve).

– T4 is converted to T3, reverse T3, T3 sulfate and T3 ace4c acid.

–  If T4 is normal and T3 is low, think of adrenal stress. Geuchot. Physiological and pathological varia2ons in saliva cor2sol. 1982 LoPres4. Thyroid response in cri2cal illness.1997

Impact of Adrenal Stress Syndrome Gastrointes4nal Func4on

– High cor4sol suppresses secretory Immunoglobulin A (sIg A) – High cor4sol contributes to dysbiosis – High cor4sol causes thinning of the GI lining – Food allergies/sensi4vi4es ac4vate the GALT and place the body in an alarm pa]ern

– High cor4sol decreases gastric and colonic mo4lity causing GERD and cons4pa4on

Cunningham-‐Rundies. 1978, 1979 Guhad. Salivary IgA as a marker of social stress in rats. 1996. Soderholm. Stress and the gastrointes2nal tract. 2001

Gut Brain Axis

•  A bidirec4onal communica4on system between the brain and gastrointes4nal systems.

•  Communica4on occurs along immunologic, neural, and biochemical pathways.

•  Gut microbiota can effect both brain development and behavior.

•  Stress also can alter the composi4on of Gut microbiota.

Maternally seperated rats have increased cortisol and increased BDNF. Bifidobactrium replacement improves hippocampal BDNF, but not in maternally seperated rats.

Stress and the Gut

•  When young rats are separated from their mothers, the layer of cells that line the gut becomes weakened and more permeable.

•  Dr. Mayer Emeran, professor of physiology and psychiatry at UCLA reports that 70 percent of his pa4ents with chronic GI disorders had early childhood traumas.

•  He has also found that the majority of pa4ents with anxiety and depression have some

altera4on in their GI func4ons.




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Stress and Friendly Bacteria

Prenatal stress alters the bacterial coloniza4on of the gut in infant monkeys. Stress reduced the overall numbers of bifidobacteria and lactobacilli. (Bailey, 2004)

Exposure to stress in mice reduces the number and diversity of commensal microbial popula4ons while leading to increased coloniza4on by Citrobacter roden4um. (Bailey, 2010)

Reduced anxiety-‐like behavior and central neurochemical change in germ-‐free mice

Neurogastroenterology & MoQlity Volume 23, Issue 3, pages 255–e119, March 2011

•  The presence of gut microbiota regulates the set point for hypothalamic-‐pituitary-‐adrenal (HPA) axis ac4vity.

•  Germ-‐free mice, compared to SPF mice, exhibited basal behavior in the EPM (maze) that can be interpreted as anxioly4c.

•  Altered GF behavior was accompanied by a decrease in the N-‐methyl-‐D-‐aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-‐derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus.

•  The presence or absence of conven4onal intes4nal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain.

Probio4cs as Psychotropics Emerging literature is showing the beneficial effect of oral probio4cs on mood and anxiety symptoms.

In a double blind, placebo-‐controlled randomized parallel group study, daily use of probio4cs reduced psychological distress. (Messaoudi, 2010)

A number of studies have shown the an4-‐anxiety effects of probio4c use in pa4ents with medical condi4ons. (Silk, 2009; Sullivan 2009; Patel, 2008; O’Brien, 2004)

Impact of Adrenal Stress Syndrome Immune

– Elevated cor4sol •  Low sectretory Ig A, which affects mucosal barriers like

–  GALT (gut associated lymphoid 4ssue) –  BALT (bronchi associcated lymphoid 4ssue) –  BBB (blood brain barrier) –  Skin

•  Low wbc •  Atrophy of thymus •  Decreased IL 2 produc4on •  Shortened telomeres in wbc Daynes, R. 1990

Adrenals and Immune Cont’d “Neurotensin is increased in serum of young children with auQsQc disorder”

J Neuroinflamma4on. 2010; 7: 48. Theoharis C Theoharides

– Neurotensin could act with CRH (cor4cotropin releasing hormone) to s4mulate mast cells and lead to neurogenic inflamma4on

– NT s4mulates lymphocytes, ac4vates T cells, and enhances interleukin 1 from macrophages

– Select flavinoids inhibit release of proinflammatory mediators from mast cells

Mitochondria and Stress “Dynamic regula4on of mitochondrial func4ons by glucocor4coids” Proc Natl Acad Sci USA. 2009 Feb 2. Du J and Manji H.

•  In brain cells of rats treated with cor4costerone, GR latched onto Bcl-‐2, a protein that affects how substances get in and out of mitochondria. Brief increases of cor4costerone enhance mitochondrial func4ons.

•  High doses or long-‐term treatment with cor4costerone led to decreased levels of GR and Bcl-‐2 in mitochondria. Similar results occur in rats exposed to chronic stress.

•  Cor4sol boosts mitochondrial func4ons to provide cells with more energy for coping with and adap4ng to acute challenges.

•  However, chronically elevated levels of cor4sol may reduce mitochondria cell func4oning. The decrease in proper cell func4on may be at the root of certain chronic physical and mental illnesses.




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Stress -‐Induced Oxida4ve Changes in Brain CNS and Neurological Disorders Oct. 2006. Madrigal, M.

•  Numerous systems and organs are affected by stress. •  Stress causes the atrophy of hippocampal dendrites or even the

reduc4on of the hippocampal size observed in brains from subjects exposed to severe or chronic stress.

•  Excess glucocor4coids can result in neurotoxicity, modifica4ons in energy metabolism, and an increase in excitatory amino acids such as glutamate .

•  Leads to the ac4va4on of TNFα convertase (TACE) and TNFα release in brain of rats subjected to restraint stress. TNFalpha ini4ates the transloca4on of the transcrip4on factor NFκB to neuronal nuclei.

•  NFκB ac4va4on results in the induc4on of iNOS and COX2, two enzymes responsible for a great por4on of the neurological damage produced in models of stress.

Zinc Deficiency and Stress •  There is a growing body of literature suppor4ng the associa4on between zinc and ADHD, anorexic behaviors, depression, and anxiety.

•  Zinc plays a role in serotonin and glutamate ac4vity as well as oxida4ve stress.

•  Zinc deficient animals exhibit anxiety like behaviors.

•  Rats fed a zinc deficient diet were shown to have higher levels of cor4costerone following exposure to stress.

Cope, et al. Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):685-‐9

Bacopa helps oxidative stress, anxiety, and stimming in autistic rats

Chronic Stress

HPA Axis

Adrenal Stress

Neurotransmi]er Imbalances Abnormal Cor4sol

Hormone Imbalances Decreased Immunity

Gastrointes4nal Disorders Blood Sugar Dysregula4on

DYSAUTONOMIA

Dysautonomia

Dysfunc4on of the Autonomic Nervous System (ANS)

– Nervous System – Immune System – Gastrointes4nal System – Cardiovascular System – Endocrine/Hormone System

Autonomic Nervous System

Fight and Flight = Sympathetic Nervous System

Rest and Digest = Parasympathetic Nervous System




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Symptoms of Dysautonomia •  Excessive fa4gue, sleep disrup4on •  Excessive heat or cold •  Loss of swea4ng or excessive swea4ng •  Excessive urina4on and thirst, salt cravings •  Lightheadedness, dizziness, orthosta4c hypotension, syncope •  Rapid or slow heart rate •  Noise and Light Sensi4vity •  Tremulousness, Dysequilibrium •  Feelings of anxiety or panic •  Headaches, nerve pain, numbness •  Facial flushing •  Cons4pa4on, Diarrhea, Nausea, Reflux, Dysmo4lity •  Seizures

Possible Signs and Symptoms of Dysautonomia in ASD

•  Poor self regula4on/tantrums •  Light and Sound sensi4vi4es •  Irritable when misses meals •  Difficult transi4oning to new environment

– Light, sound, temperature changes

•  Need for deep pressure to help regulate •  Head banging •  Food refusal •  Licking behavior (salt seeking)

Reduced Cardiac Parasympathe4c Ac4vity in Children with Au4sm

Xue Ming Brain and Development October 2005

•  Many of the clinical symptoms of au4sm suggest autonomic dysfunc4on.

•  The aim of this study (n=28), (control=117) was to measure baseline cardiovascular autonomic func4on in children with au4sm.

•  The results suggest that there is low baseline cardiac parasympathe4c ac4vity with evidence of elevated sympathe4c tone in children with au4sm whether or not they have symptoms or signs of autonomic abnormali4es.

Heart Rate Variability Mul4scale Model for the Assessment of Autonomic Dysfunc4on in Human Endotoxemia

Foteinou PT Physiol Genomics. 2010 Jun

Severe injury and infec4on are associated with autonomic dysfunc4on. The realiza4on that a dysregula4on in autonomic func4on may predispose a host to excessive inflammatory processes has renewed interest in understanding the role of central nervous system (CNS) in modula4ng systemic inflammatory processes. Assessment of heart rate variability (HRV) has been used to evaluate systemic abnormali4es and as a predictor of the severity of illness.




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Causes of Dysautonomia

•  Autoimmune disorders esp. Type I diabetes •  Brain injury •  Neurodegenera4ve diseases •  Exposure to toxic chemicals •  Infec4ons (viral) •  Gene4c factors •  Hereditary connec4ve 4ssues diseases •  Pregnancy •  Physical Trauma •  Unknown

Autonomic Nervous System (ANS) •  Act in opposi4on •  Affects

•  heart rate •  diges4on •  respira4on rate •  saliva4on •  perspira4on •  diameter of the pupils

•  urina4on •  sexual arousal

•  Neurotransmi]ers •  Acetylcholine •  Norepinephrine and Epinephrine

The Vagus Nerve •  Main nerve of the parasympathe4c nervous system •  Inherently communicates with the splenic nerve to suppress TNF alpha produc4on in the spleen and modulate immune func4on. (Dr. Rosas-‐Ballina)

•  Efferent or Dorsal Motor Vagus Nucleus (DMV) •  Motor to Pharynx, Larynx, GI, Bladder

•  Afferent or Sensory (80%) •  Back to the brain from the ear, tongue, larynx, GI tract

•  Releases ACh (acetylcholine) •  Nico4nic Receptors •  Muscarinic Receptors

Neurotoxic Brainstem Impairment as Proposed Threshold Event in Autistic Regression

McGinnis WR, Miller VM, Audya T and Edelson S.

CRC Press 2009

•  Oxida4ve Stress, inflamma4on and immune abnormali4es seen in ASD are related to a toxic injury to the primi4ve brainstem.

•  Impairment of the dorsal vagal complex (DVC) could account for the cardinal features of au4sm.

•  Regression aier age 1 could be triggered by toxic effects on small areas of the brainstem that lack blood-‐brain-‐barrier (BBB).

Vagus Nerve Cools Gut Inflamma4on Mice exposed to sodium dextran sulfate to simulate inflammatory bowel disease. Mice with intact vagus nerve exhibit less inflammation in the gut. Mice with vagus nerve cut produced heightened inflammation in the gut. The vagus nerve by releasing Acetylcholine stimulates T regulatory cells that lower inflammation. O'Mahony C. Loss of vagal anti-inflammatory effect in-vivo visualization and adoptive

transfer. Am J Physiol Regul Integr Comp Physiol. Aug 12 2009.

Slow –Transit Cons4pa4on Intern. Symposium of Gastrointes4nal Mo4lity, Copenhagen, Denmark, 1996 Altomare, et al…

•  Autonomic neuropathy thought to play a role in the pathogenesis of slow transit cons4pa4on.

•  Common issues-‐ eg. reflux, gallbladder dysmo4lity, decreased gastric emptying, delayed orocecal transit 4me, abnormal recto-‐anal inhibitory reflex, decreased rectal sensi4vity.

•  Autonomic neuropathy in 14/18 pts. (SST=sweat spot test) •  Slow transit cons4pa4on is associated with impaired

func4on of other gastrointes4nal organs. •  Severe cons4pa4on may be the main complaint of a

systemic disease involving several organs and possibly the autonomic nervous system.




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Basic Biomedical Strategy •  History and Physical Examina4on •  Laboratory Tes4ng •  Clean Up

–  Environment –  Diet –  Gut –  Stressors

•  Start Founda4onal Nutrients •  Address HPA Axis and Dysautonomia •  Treat Underlying Immune Issues and Inflamma4on •  Support Detoxifica4on Pathways, Methyla4on,

Sulfa4on, Glutathione •  Address Mitochondrial Dysfunc4on •  Heavy Metal/Chemical Detoxifica4on

History

•  Adrenal Stress •  Glycemic Control •  Autonomic Func4on

– Temperature Regula4on – Swea4ng – GI Mo4lity – Sensory Issues – Sleep pa]erns

Signs and Symptoms of Adrenal Stress Adrenal HypofuncQon

Cannot stay asleep Craves salt Slow starter

Aiernoon fa4gue Dizziness on standing Aiernoon headaches

Low cor4sol Hi epinephrine High anxiety

Low glucose (hypoglycemia) Craves sweets

Irritable if meals missed Be]er with meals

Adrenal HyperfuncQon

Cannot fall asleep Perspires easy Lots of stress Weight gain

Craves sweets aier meals Sleepy aier meals Wakes up 4red Hyperac4vity

High cor4sol High glucose (hyperglycemia)

Low melatonin Insulin resistance

High Testosterone (women) High Estrogen (men)

Physical Signs Associated with Dysautonomia

•  Low or High body temperature •  Lack of sweat or too much sweat •  Dry sand paper skin •  Abnormal pupillary response •  Poor skin turgor •  Low blood pressure (orthosta4c hypotension) •  Abnormal beat to beat variability •  Ridges or bite marks on the sides of the tongue •  Hyperlaxity in joints Rubin LS. PaCerns of pupillary dilata2on and constric2on in psycho2c adults and au2s2c children. 1961 64

Orthosta4c Hypotension •  Normally when a person goes from lying down to standing,

the systolic blood pressure should elevate 4-‐10 mm Hg. •  In hypoadrenia, the systolic blood pressure from lying to

standing will either stay the same or drop. This systolic drop is usually between 5 to 10 mm. Hg., but some4mes as much as 30-‐40 points, known as the Ragland effect, or postural hypotension, and which is reported in over 90% of hypoadrenic persons.

•  Blood pressure should always be checked in three posi4ons: siyng, then lying, then standing. From recumbence to standing, the systolic blood pressure should rise 4-‐10 points.

•  If the blood pressure drops, suspect func4onal hypoadrenia.

Lab Op4ons HPA Axis •  Blood Sugar •  Insulin •  Cor4sol •  Aldosterone •  DHEA •  Testosterone •  Estrogen/Progesterone •  ACTH and ACTH s4m test •  Cholesterol •  TSH, T3, T4




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Evalua4on of Stress Symptoms

•  Physical exam findings •  Non-‐invasive tests

– Heart rate variability – Salivary DHEA and cor4sol – Cutaneous sweat patches for neural and immune biomarkers

– Urinary catecholamenines – Tilt table tes4ng

Mayo / Medical Center Autoimmune Dysautonomia Evalua4on

GANGLIONIC ACETYLCHOLINE RECEPTOR (ALPHA3) AUTOANTIBODY NEURONAL VOLTAGE-GATED POTASSIUM CHANNEL (VGKC) AUTOANTIBODY N-TYPE CALCIUM CHANNEL ANTIBODY P/Q-TYPE CALCIUM CHANNEL ANTIBODY ACETYLCHOLINE RECEPTOR (MUSCLE ACHR) BINDING ANTIBODY GLUTAMIC ACID DECARBOXYLASE (GAD65) ANTIBODY ASSAY ANTINEURONAL NUCLEAR ANTIBODY-TYPE 1

Special Environmental and Dietary Considera4ons

•  Avoid chemical endocrine disruptors especially pes4cides, plas4cizers, BPA, phthalates, organophosphates…

•  Low glycemic, Limit sugar and carbs •  Protein and fiber with meals and snacks •  3 meals, 3 snacks per day •  Bed4me snack with protein •  Limit hormones and excitotoxins in food •  Exercise

Address HPA Axis •  Adaptogenic Herbs

–  Panax Ginseng –  Siberian Ginseng (eleutherococcus) –  Ashwagandha (withania somnifera) –  Rhodiola –  Holy Basil (tulsi)

•  Other –  Vitamin B5/Pantothenic Acid –  Licorice/Glycyrrhizin (increases cor4sol) –  Phospha4dyl Serine(lowers cor4sol) –  Glandulars (Adrenal Cor4cal Extract) –  Hormones (Pregnenolone, Progesterone, DHEA)

•  Gaffny. Panax ginseng and Eleutherococcus sen2cosus may exaggerate an already exis2ng biphasic response to stress via inhibi2on of enzymes which limit the binding of stress hormones to their receptors. 2001

•  Spasov. A double-‐blind placebo controlled pilot study of the s2mula2ng and adaptogenic effect of Rholiola rosea on the stress induced fa2gue of students…2000

Support Blood Sugar Regula4on

•  Chromium •  Vanadium •  Gymnema sylvestre •  Bi]er melon •  Cinnamon •  Alpha Lipoic Acid •  Carni4ne •  Omega 3 EFA




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Address Dysautonomia

•  Down-‐regulate Sympathe4c – Down regulate excitatory neurotransmi]ers

•  NE and Epinephrine (adaptogens) •  Glutamate (meman4ne, Mg, Li)

•  Up-‐regulate Parasympathe4c •  Acetylcholine (phospha4dylcholine, serine) •  Acetylcholinesterase Inhibitors (galantamine)

•  Salt •  Beta blockers

Address Neuroendocrine System

•  Hippocampus – Secre4n (nasal, transdermal, IV) – Phospha4dyl Serine – Lower Cor4sol

•  Amygdala – Oxytocin (nasal, oral)

•  Blood-‐Brain-‐Barrier – Vit A, Vit E, Saccromyces boulardii

Posi4ve Ways of Handling Stress •  Breathing (www.heartmath.org) •  Medita4on/Prayer/Quiet Time •  Exercise-‐ low impact •  Singing, Chan4ng •  Healthy Diet and Bed4me Rou4nes •  Improving self esteem/confidence (aytude) •  Sleeping •  Just Relaxing and Slowing Down •  EFT (emo4onal freedom technique) •  Biomedical Interven4ons

Thank You! And don’t forget to take a deep

breath!! www.truehealthmedical.com