alcat food sensitivity and intolerance test
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Anxiety and Your PatientA holistic, integrative approach for the general
practitioner-
www.alcat.com
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Epidemiology
Journal Clinical Psychiatry- mostcommon psych disorder
15.7 million in the US
30% seek treatment
Present to general practitioners more
than psychiatrist
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What is Anxiety
Persistent fear response withoutidentifiable specific trigger or
Prolonged response
Starts fight or flight response
Anxiety increases risk of inflammatory
diseases
More prone to mistakes, less
productive
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Genetic?
Studies show may be geneticsusceptibility with variants of retinoid-
related orphan receptor alpha (RORA)
gene to PTSD Gene primary function to protect brain
from stress
Gene Variant of BDNF geneMet66Met- smaller hippocampus on
imaging and higher response
amygdala to emotional stimuli withCopyright 9/11/2012
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Mediators- B.I.G
Brain (neuroendocrine)
Immune System- surveillance,
Gut
Vagus nerve 2 way communication
system between brain and gut
All interact to form super information
highway
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Brain-Theories and
Substances Trigger
Arrives amygdala
To Locus Cereleus
Activation of sympathetic system
Prefrontal lobe
Response
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Brain Connection- Pathway
rTrigger
Amygdala
LocusCereleus
NE
CRH
ACTHAdrenal
Stimulation
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Theories and Substance
Amygdala stores fear memories
Used Pavlovian conditioned and
unconditioned stimulus
Substances affect amygdala canescalate or ameliorate anxiety
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Brain Connection
Locus Cereleus primary NE center inbrain
LC can be affected by other NT
LC connects to all parts of brainincluding hypothalamus
NE play role in HTN, behavioral
changes and modulates HPA axis
Increased cytokines increase NE in
hypothalamus via LC neurons
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Brain Connection
Several factors seem to play a rolehere
NT such as GABA, Serotonin and
Norepinephrine and glutamate havebeen assigned significant roles
The HPA with CRF axis gets activated
as well Cytokines can form de novo in the
brain and trigger responses
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Brain Connection
The major neurotransmittersimplicated in the anxiety response
GABA
NE
Serotonin
Glutamate
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Brain Connection
Serotonin is known as inhibitory NT
Derived from trytophan
Majority found in gut (90%)
Rest brain and platelets
Foods that irritate gut can caused
excess release of serotonin leading to
diarrhea (goal is to expel substancecausing issue)
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Brain Connection
Serotonin depletion in prefrontalcortex leads to anxiety symptoms
Serotonin has 7 subtype receptors
5HT1a- related to anxiety
5HT3 in the chemoreceptor center
brain can be stimulated by excess
serotonin and cause nausea andvomiting
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Brain Connection
GABA major inhibitory in the brain
Also found in Gut
Regulation of GABA system in
amygdala important part of anxietypathology
Pathway conversion excitatory
Glutamate to GABA via enzymeglutamate decarboxylase
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Brain Connection- GABA
3 types GABA receptors- A, B. C
Deficiency in GABA receptors (A)- led
to hyper activation of HPA axis
GABA-A (fast)
binding increase clconductance so hyperpolarize post
synaptic neurons to decrease
excitation GABA-B- inhibit Ca channels to
reduce NT release, and K channels to
decrease excitability Copyright 9/11/2012
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Glutamate
Excitatory NT (most abundant)
Several studies indicate that
modulating glutamate receptors can
improve anxiety Mechanism not fully elucidated
Glial cells responsible removal of
glutamate Dysfunction or reduction leads to
glutamate toxicity
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Glutamate
Thought to be mediated throughNDMA receptor
Needs glutamate, glycine and voltage
for activation and opening channels Open- Calcium influx
Excess calcium- neuronal injury
Fine line because activation NDMAneeded for memory and learning
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Norepinephrine
Increases symptoms of anxiety
When administered symptoms of
anxiety- HR, diaphoresis, etc.
Controversy if NE from LC causative
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Brain Connection-
Other substances CCK 4- provokes anxiety
BDNF- responsible for health, growth
and plasticity of nerves (adaptability)
BNDF protects neurons fromglutamate toxicity
Oxytocin- role in social phobias
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Brain Connection- BDNF
Human study showed depressedindividuals with lower BDNF
Those with lowest BDNF levels did not
respond as well to anti-depressanttreatment
Several studies show BDNF facilitates
function of anti-depressant esp. SSRI
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Immune Connection
The immune system is thought to betrigger
Chronic GI inflammation increases
inflammatory cytokines and anxietybehavior
Immune system and neuroendocrine
share many receptor sites and ligands
Cytokines (produced by immune system
and also by brain) can regulate stress
response in brain as well as endocrine
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Immune connection
Immune system when triggeredproduce cytokines
Ex. IL-6, IL-1, IL-2, IFN-gamma, TNF,
Peripheral cytokines can cross BBB
Stimulate HPA axis as well as cause
brain (glial Cells) to produce de novo
cytokines Excess IL-6 act on neurons increase
anxiety and cognitive deficits
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Immune Connection
Cytokine can activate HPA axis
Increase CRH
CRH sensitize cells and facilitate
effect of cytokines like TNF
TNF alpha injected in amygdala
facilitated ETOH withdrawal anxiety
Inhibitor of CRH receptor decreasedmagnitude of anxiety response
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Immune Connection
Interferon gamma stimulates enzymeindoleamine2,3 dioxygenase (IDO).
This degrades Tryptophan
(responsible for serotonin formation)to other inflammatory substances such
as Kynurenine
17 B-estradiol could increases INFgamma thereby potentially increasing
inflammation
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Immune Connection
Aging increases Cytokines such asINF gamma, TNF alpha
Dysregulates HPA feedback
mechanism thereby increasing cortisollevels
Cortisol affects metabolism of
tryptophan towards inflammatoryalong with direct effect hippocampus
Theorized one of reasons elderly more
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Immune Connection
Studies show that TCA like imipramineand SSRI have anti-inflammatory
effect
Decreases levels of IL-2, IL-1, TNF, IL-6, INF gamma
These substances have immediate
effect on NE and Serotonin but takeslonger for clinical benefits (about time
that it takes to have effect on
cytokines Copyright 9/11/2012
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Gut Connection
Gut has over 100 million neurons
90% visceral neurons have connection
with brain
95% all serotonin found in gut
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Gut Connection
Studies showed that changingbacterial flora in mice changed
behavior
Colonized germ free mice with gutflora from active or passive mice
would change behavior accordingly
Mice treated with antibiotics- anxietyreduction.
Stopped antibiotics flora and anxiety
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Gut Connection
Changes seem to be associated withchange in BDNF (linked to anxiety anddepression)
Stressor exposure changed bacterialflora in gut (decrease genusBacteroides and increase Clostridium)
Stressor also increased inflammatory
cytokines (IL-6, MCP-1) furtheraffected other bacterial flora
IL-6 inflammatory cytokine
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Gut Connection
Evidence that LactobacillusRhamnosus augments GABA function
in brain via vagus nerve from gut
(results lost with vagotomy)Also lowered corticosterone levels
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Gut Connection
Infectious colitis induces anxietyBifidobacterium longum NCC3001
improved anxiety (results lost with vagotomy)
Bifidobacterium longum normalizedbehavior and BDNF mRNA but did not
affect cytokine or kynurenine levels
Enbrel- decreased cytokines andimproved anxiety but did not affect
BDNF
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Gut Connection
Since inflammation can directly affectflora of gut and flora can affect
behavior
Could anything such as foodsensitivities cause inflammation in gut
and thereby exacerbate anxiety
symptoms Personal food sensitivity such as
ALCAT may be an important adjunct
as testing looks at immune responseCopyright 9/11/2012
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Gut Connection
Study showed stress contributed todevelopment of food allergies by
increasing gut permeability therefore
increased uptake of food antigen Bacteria like H. Pylori has been shown
to do the same in gastric mucosa, also
increasing food sensitivityActivation of immune system and
cytokines
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Gut Connection
Food sensitivities trigger gutpermeability
Part treatment remove triggers
Heal gut
Bifidobacterium Animalis Lactis LKM
512 found to help to keep tight
junction gut and decrease permeability Decreased inflammation in elderly
Seems to suppress inflammatory
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What to do?
When and if possible identify trigger Gut symptoms- know can be variety of
things from food sensitivity, to
infectious or inflammatory trigger suchas IBD to emotional stress (rememberchanges flora)
ALCAT may be helpful
Remove and or treat trigger Consider probiotics with
neuromodulatory effect
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What to do
Consider other substances todecrease inflammatory cytokines while
treatment is on going (curcumin, fish
oil, and resveratrol, andrographis)-?medical food
Tea Tree Oil (inhalation)- decreases
TNF alpha, IL 1 If over weight start weight loss
Remember Adipocytes can generate
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What to do
German Chamomille- inhibited releaselipopolysaccharide which induce
macrophage prostaglandin E2 (LOX-2
inhibitor Maybe possess some anti-microbial
properties (gut dysbiosis)
Contains Apigenin flavonoid- studyshow mild sedative via inhibition
NDMA-R
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What to do
I have found neurotransmitter testinghelpful
Even though no info on receptors, etc.
I find it helps me to chosesupplements or meds
Check for easy nutrient deficienciesB12, folate, red blood cell magnesium
(easier than loading test) Check cortisol/ACTH levels - helps in
choosing tx
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What to do- herbal
Valerian- blocks glutamate receptor Jujube (Ziziphysis Spinosa)- inhibits
glutamate receptor to decrease
excitability
Kava- shown to improve anxiety
Concern with liver issues due to
quality of Kava, parts used andinappropriate dosage
Passion Flower extract thought to
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What to do
Tryptophan- just remember thatinflammation can turn a good AA bad
Studies do not support St. Johns Wort
for anxiety Magnesium- modulates NDMA-R slow
influx calcium- protecting neurons
Vitamin B12 studies show protectsneurons NDMA-R glutamate toxicity
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What to do
L-Theanine- studies suggests worksthru GABA- A receptors
Other studies show affect on serotonin
and dopamine NT Personally noted that if dopamine on
NT test high, theanine may haveslightly anxiogenic affect
Good news- neuroprotective bydecreasing formation glutamine toglutamate
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What to do- HPA Axis
Lavender Essential oil stimulates PNSto decrease excitability
Lemon Balm- inhibitor of GABA
transaminase (enzyme clears GABA)Address HPA axis
Stress management
Cognitive therapy (enhanced with D-cycloserine for specific phobias)
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What to do-HPA
Magnolia officianlis (honokiol andmagnolol)- decrease corticosterone,
increase 5HT in hippocampus,
antimicrobial, decrease TNF alpha
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What to do
If menopausal consider there may bea hormonal component
Changes in hormones such as
estrogen, progesterone andtestosterone can contribute to anxiety
symptoms
I could correct other issues first tooptimize results
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What to do- Hormones
Several studies suggest estradiol canbe anxiolytic
Estrogen increases the mRNA for
trytophan hydroxylase enzyme (ratelimiting step in production of serotonin
Effects in dorsal raphe and seems to
occur binding ER beta
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What to do- hormones
Can increase proinflammatorycytokines
Avoid with autoimmunity
? One study suggest this effect maybe at least in part influenced by
presence of hydroxylated estrogens
(2,4,16) and cortisol Personal approach r/o autoimmunity,
correct inflammation if present before
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What to do- Hormones
Progesterone- anxiolytic or anxiogenic Several studies suggest that effect on
GABA receptors
Conversion to allopregnanelone
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What to do- Pharmacological
SSRI, 5HT1a-R agonist- decreaseinflammation, increase serotonin (E.g.
Lexapro, Buspar)
Also seem to modulate NDMA-R Benzodiazepene- GABA
B-Blocker (Inderal)- performance
anxiety (stage fright, exams, etc.) Block sympathetic symptoms, also
acutely decrease endorphin levels
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Some Concerns
Prolonged use SSRI can lead toosteoporosis
Shown eventual decrease in serotonin
levels below baseline with chronic use Benzodiazepenes addictive potential
Long term effect of beta blocker-
depression, memory loss etc.
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What to Avoid
Spirulina- increases, TNF alpha Echinaccea- can potentially increase
IL-6, TNF alpha
?? Honey- works by increasing TNFalpha, IL 6, IL 1
Remember cytokines can stimulateHPA axis as well as activate amygdala
and LC =NE anxiety Caffeine blocks its receptors
adenosine that slows HR and calms-
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THANK YOU
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