Alcat Food Sensitivity and Intolerance Test

7/30/2019 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

system and behavior Copyright 9/11/2012


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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

prone to depression/anxietyCopyright 9/11/2012


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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

returned to baseline Copyright 9/11/2012


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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

bacteria Copyright 9/11/2012


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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

cytokines as well Copyright 9/11/2012


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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

have GABA agonist propertiesCopyright 9/11/2012


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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

this step Copyright 9/11/2012


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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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Alcat Food Sensitivity and Intolerance Test

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