10/5/2012

1
ClinicalCorrectionforAdrenal
andNeurotransmitterImbalances
ErinLommen,ND
CEO&AssociateMedicalDirector
LabrixClinicalServices,Inc.
Restorative2012
Understandthephasesofadrenaldysfunctionas
theyrelatetoHPAandneuroendocrineactivity
ReviewHPAaxisandbrainphysiologyasit
pertainstotheregulationofadrenalfunction
ObtainanoverviewofPTSDanditsramifications
asabasisforunderstandingroutineclinical
presentationandtreatment
Learnnewtreatmentprotocolsbasedon
advancedprinciplesandrefineexistingtreatment
approachesforthesuccessfultreatmentofHPA
axisdysfunctionandneuroendocrineimbalances.
Angina
Asthma
AutoImmunediseases
Alzheimer's
Cancer
Cardiovasculardisease
ChronicFatiguesyndrome
DepressionandAnxiety
Diabetes(adultonset,typeII)
Fibromyalgia
Headaches
Hypertension
Hormonalimbalances
Immunesuppression
Irritableboweldisease
Inflammatoryboweldisease
Menstrualirregularities
Premenstrualtension
Rheumatoidarthritis
Ulcerativecolitis
Ulcers
Rheumatoidarthritisisassociated
withlowcortisollevels.
RA symptomsofpain
worseinthemorningand
improvingasthedaygoeson.
Theflatteningoftheirdiurnal
rhythmisthoughttoplayaroleinthedisease.
Lowdosecortisoltherapyhelpssymptomaticallywith
RAandimprovestheslowingoftheprogressionofthe
disease.
Stressasariskfactorinthe pathogenesisofrheumatoidarthritis.
Cutolo M,StraubRH. Neuroimmunomodulation. 2006;13(56):27782. Epub 2007Aug6.
10/5/2012
2
Engaginginamemorytask
activatestheimmune
system
Passivelywatchingaviolent
videoweakensimmunity
OhioStateUniversityPsychophysiology,SeptemberOctober2001
dramaticallyincreasestheabilityof
exogenouschemicalstopassthroughthe
bloodbrainbarrier.DuringtheGulfWar,
Israelisoldierstookadrugtoprotect
themselvesfromchemicalandbiological
weapons.Thispharmaceuticalagen
underusualcircumstances,isnot
expectedtocrosstheBBB,but
researchersobservedthatwiththestress
ofwar
Nearly25%ofthesoldierscomplainedof
headaches,nausea,anddizziness
(symptomswhichoccuronlyifthedrug
reachesthebrain).
Henceanincreasedthepermeabilityofthe
BBB...
Journal ofAppliedPsychology, October2000
GaryEvansandenvironmentalpsychologistsatCornellfound
thatlowlevelnoiseinopenstyleofficesresultedinhigher
levelsofstress,andlowertaskmotivation.
Fortyexperiencedfemaleclericalworkers(averageage37)were
assignedtoathreehourworkstudy toeitheraquietofficeor
onewithlowintensityusualambientofficenoise(including
speech).
Theworkersinthenoiseinclusiveenvironmentsexperienced:
significantlyhigherlevelsofstress(asmeasuredbyurinary
epinephrine)
made40%fewerattemptstosolveanunsolvablepuzzle,
andmadeonlyhalfasmanyergonomicadjustmentstotheir
workstations,comparedtotheircolleaguesinquietoffices.
Thesimulatedopenofficenoiseelevatedworkers'urinary
epinephrinelevels,isindicativeofmotivationaldeficits:
Participantswerealsolesslikelytomakeergonomic,postural
adjustmentsintheircomputerworkstationwhileworkingunder
noisy,relativetoquiet,conditions.Posturalinvarianceisarisk
factorformusculoskeletaldisorder.
Althoughparticipantsinthenoiseconditionperceivedtheir
worksettingassignificantlynoisierthanthoseworkingunder
quietconditionsdid,thegroupsdidnotdifferinperceived
stress.Pointstopotentialhealthconsequencesoflongterm
exposuretolowintensityofficenoise
Evans,GaryW.;Johnson,Dana
JournalofAppliedPsychology,Vol.85(5),Oct2000,779783.
Includedinnoiserelatedproblems:
highbloodpressure
pepticulcers
cardiovasculardeaths
strokes
suicides
degradationoftheimmunesystem,
impairmentoflearning
increaseinaggression
decreaseincooperation
New York Times, March6, 1990
SerotoninModulationofSensory Inputstothe LateralAmygdala: Dependency on Corticosterone, Journalof
Neuroscience, 15November1998,18(22)95299538,GraceE Stutzmann, BruceS McEwenandJosephE Ledoux
10/5/2012
3
Medicalinsider.com
Hypoadrenia (ICD10255.7billablediagnosis)
code
Couldtherebeadditionalconsiderationsfor
whatleadstohypoadrenia?
ICD10:F43.1isnotabillablediagnosiscode
andcannotbeusedtoindicateamedical
diagnosis.
PTSDisamentalhealthconditionthat's
triggeredbyaterrifyingevent.
Symptomsmayincludeflashbacks,nightmares
andsevereanxiety,aswellasuncontrollable
thoughtsabouttheevent.
DysfunctionoftheHPAaxisinthestressresponse
hasbeendocumentedinanumberofpsychiatric
disorders(Loetal.,2008;Pariante andLightman,
2008;Sinha,2008),includingPTSD.
10/5/2012
4
Experienceoftraumaorterror
responseinvolvedisintensefear,horrororasenseofhelplessness
Reliveexperiencesoftheevent,suchashavingdistressingimagesand
memories,upsettingdreams,flashbacksorevenphysicalreactions
Attemptstoavoidsituationsorthingsthatremindthemofthetraumatic
eventorfeelasenseofemotionalnumbness
feelingasifconstantlyonguardoralertforsignsofdanger,whichmay
makeitdifficulttosleeporconcentrate
symptomslastlongerthanonemonth
Thesymptomscausesignificantdistressinlifeorinterferewithabilitytogo
aboutyournormaldailytasks
Staysawayfromplaces,events,orobjectsthatareremindersofthe
experience
Feelingemotionallynumb
Feelingstrongguilt,depression,orworry
Losinginterestinactivitiesthatwereenjoyableinthepast
Havingtroublerememberingthedangerousevent.
Beingeasilystartled
Feelingtenseoronedge
Havingdifficultysleeping,and/orhavingangryoutbursts.
Angerandirritability
Guilt,shame,orselfblame
Substanceabuse
Feelingsofmistrustandbetrayal
Depressionandhopelessness
Suicidalthoughtsandfeelings
Feelingalienatedandalone
Physicalachesandpains
Strongfoodcravings(sugarandsimplecarbohydrate)
6.8%USApopulation
Maybeashighas24%insub
populations(military)
Kessleretal2005ab
Millikenetal2007
Arecentmetaanalysisnotedthatlowerlevels
ofbasalcortisolinplasmaandserumwere
foundinpatientswithPTSDcomparedto
healthycontrolswithnopriortraumaexposure,
butnotnecessarilycomparedtocontrolswitha
historyoftraumaexposure(Meewisse etal.,
2007).
Yehudaandcolleaguesdemonstratedthat
combatveteranswithPTSDshowedgreater
cortisolsuppressionthandidcombatveterans
withoutPTSDornormalcontrols(Yehudaetal.,
1995)
Fatigue Weakness Unexplainedhairloss
Nervousness Difficultybuildingmuscle Irritability
Mentaldepression Difficultygainingweight Apprehension
Hypoglycemia Palpitations(heart fluttering) Inability toconcentrate
Excessivehunger Tendencytowards
inflammation
Momentsofconfusion
Indigestion Feelingsoffrustration Poormemory
Alternatingdiarrheaand
constipation
Osteoporosis Lackofenergy
Autoimmunediseases Lightheadedness Dizzinessthatoccursupon
standing
Poorresistancetoinfections Lowbloodpressure Insomnia
Food/inhalant allergies PMS Cravings forsweets
Dryandthin skin Headaches Scantyperspiration
Alcoholintolerance Lowbodytemperature
Developmentofthe human adrenal zona reticularis: morphometric and immunohistochemical studiesfrombirth to adolescence.
Hui XG, Akahira J, Suzuki T, Nio M, NakamuraY, Suzuki H, RaineyWE, Sasano H.JEndocrinol. 2009 Nov;203(2):24152.Epub 2009 Sep1.
Maternalseparationwithinthe
firsttwoweeksafterdeliveryinducespermanentheightened
sensitivityoftheadrenalcortextoACTH.
Notonlythat,developmentofcortisolreceptorsthroughout
thebrainarepermanentlyinfluencedwhenbabiesaredeprived
ofmaternalhandlingthefirstweeksoflife.
Thisresultsinanalteredcortisolresponsiveness,alteredstress
regulation,alteredbehavioraladaptationandacceleratedbrain
aging.
10/5/2012
5
EarlyHumanDevelopment
Volume84,Issue10 ,Pages689697,October2008
PrenatalSSRIexposurealteredHPAstress
responsepatternsandreducedearlyevening
basalcortisollevels.
Thesefindingssuggestanearlyprogramming
effectofantenatalmaternalmood,prenatal
SSRIexposureandpostnatalmaternalcare
givingontheHPAsystem.
Thestressresponsesystemtoappropriately
react,adaptandrecoverfromthetraumatic
event.
Numerousbiologicalpathwayshavebeen
implicatedintheabnormalpathophysiologyof
PTSD
CRHCorticotropinReleasingHormone
HPAhypothalamicpituitaryAxis
Noradrenergicnorepinephrine
Serotonergicserotonin
Glutamatergicglutamine
10/5/2012
6
Lifestylechanges(sedentary,increasedsugar
andsimplecarbs)
Electronicinformationage(morescreengazing
lessexercise)
Modernlife Morestimuli
"WorkersintheUnitedStatesareputtingin
morehoursthananyoneelseinthe
industrializedworld."
LawrenceJeffJohnson thechieflabormarketeconomist.
http://archives.cnn.com/2001/CAREER/trends/08/
30/ilo.study/.August31,2001Posted:2:07AM
EDT(0607GMT)
CRHactsasbothastresshormoneanda
neurotransmitter.
CRHsecretionisincreasedincasesofanxiety
disordersandsomeformsofdepression.
European Journal ofPharmacology in2008 FlorianHolsboerandMarcus Ising
CRHisnotexclusivelyproducedinthe
hypothalamus:
1. peripheralinflammatorysites
2. inthethecaandstromalcellsaswellasincellsof
thecorporalutea
3. cellsoftheendometrium
(ADHispresentwithCRHinsomehypothalamic
cellsandisoftenreleasedsimultaneouslywith
CRHandsynergizeswithit).
IsthekeyregulatoroftheHPAaxis
Alsoexertsmajorinfluenceonthewakeand
sleepcycle
CRHinducesincreasedwaking
CRHisexcitatoryinthelocusceruleus (LC),
amygdala,hippocampus,cerebralcortex,and
someportionsofthehypothalamus.
10/5/2012
7
Inhumans,themajorityofthestudiessuggestthatthesleepof
youngindividualsisratherresistanttothearousingeffectsofCRH.
Incontrast,middleagedindividualsrespondedtoanequivalent
doseofCRHwithsignificantlymorewakefulnessandsuppression
ofslowwavesleepcomparedtobaseline.
Basedonthesefindings,weconcludedthatmiddleagedmen
showincreasedvulnerabilityofsleeptostresshormones,
possiblyresultinginimpairmentsinthequalityofsleepduring
periodsofstress.
Thesefindingssuggestthatchangesinsleepphysiologyassociated
withmiddleageplayasignificantroleinthemarkedincreaseof
prevalenceofinsomniainmiddleage.Also,peripheral
administrationofCRHisassociatedwithaREMsuppression,which
isstrongerintheyoungthaninthemiddleaged.
ourfindingsshowanimportantroleof
fibroblastexpressedCRHintheproliferation,
migration,andcytokineproductionofthese
cellsprocessesassociatedwiththeskin
responsetoinjury.
Ourdatasuggestthattheimmunomodulatory
effectsofCRHmayincludeanimportant,albeit
notexploredyet,roleinepidermaltissue
remodelingandregenerationandmaintenance
oftissuehomeostasis.
HumanCRH wasaseffectiveasACTH at
stimulating DHEA production;however,itwas
70%lesspotentthanACTHatstimulating
cortisolproduction,indicatingthatitsactions
werepreferentiallydirectedtowardincreasing
DHEAsynthesis.
The JournalofClinicalEndocrinology andMetabolismMay5,1998 CorticotropinReleasingHormoneDirectlyand
PreferentiallyStimulates Dehydroepiandrosterone SulfateSecretionbyHumanFetalAdrenalCorticalCells
1
Roger Smith,SamMesiano,EngChengChan,ShaneBrownandRobert B. Jaffe
Regulatedbycorticotropinreleasinghormone
(CRH)fromthehypothalamus
Increasesinresponsetolowlevelsof
circulatingcortisol
AlsoIncreasesinresponseto:
Stress
Fever
AcuteHypoglycemia
WaterdeprivationincreasesACTHsecretionand
adrenalsensitivitytoACTH
Newborns
Geneticpolymorphism somepeoplemay
possessreceptorsontheadrenalglandthatare
lesssensitivetoACTH.Thisisthoughttobe
seenmoreofteninatopic individuals.
Teenagersdiurnalrhythmshiftsby12hours,
withacortisolgraphpeakingatbetween9and
10am(ratherthan68am).
Adrenalinnervationfromtheadrenalmedullafacilitates
theadrenalresponseduringstress.
(Chronobiol Int.2007;24(5):96990.Diurnalandseasonalcortisol,testosterone,and
DHEArhythmsinboysandgirlsduringpuberty.Matchock RL,DornLD,Susman EJ.)
10/5/2012
8
Withinthefirst3
monthsofbirththe
fetalzonevirtually
disappearsand
productionofDHEA
ceases.
Theproductionofcortisolandaldosterone
remainsconstanthoweverandtheadrenal
cortexappearstohaveonlytwozones:Zona
fasciculata andtheZonaglomerulosa.
Developmentofthe human adrenal zona reticularis: morphometric and immunohistochemical studies frombirth to adolescence.
Hui XG, Akahira J, Suzuki T, Nio M, NakamuraY, Suzuki H, RaineyWE, Sasano H.JEndocrinol. 2009 Nov;203(2):24152.Epub 2009 Sep1.
Attention
Learning
Memory

(Wolf,2008).
(Sargant andSlater,1940).
thereisalargebodyofevidencetosuggestthatthisfunctioningis
altered,andtheremayinfactbehyperactivenoradrenergicfunction
inPTSD.(evidencesupportsautonomichyperactivityinPTSD)
Furthermorethereareimportantreciprocal
interactionsthatexistbetweentheserotonin
andNEsystems.ThefiringofNEneuronsinthe
LCisundertonicinhibitionbyprojectionsfrom
thedorsalraphe nucleus.TheuseofSSRIs
whicheffectivelyallowincreased5HTtobe
releasedindirectlyenhancesthisinhibitorytone
(Szabo andBlier,2001)whichmaybeakey
factoryinimprovingthehyperadrenergic state
inPTSD,andthedownstreamimprovementin
amygdala activation.
10/5/2012
9
Synapse. 2001Dec15;42(4):20312.
Serotonin(1A)receptorligands actonnorepinephrine neuronfiringthroughexcitatory
aminoacidandGABA(A)receptors:amicroiontophoretic studyintheratlocus
coeruleus.
Szabo ST,Blier P.
Source
NeurobiologicalPsychiatryUnit,McGillUniversity,Montral,Canada.
RevealselevatedurineNElevelscomparedto
healthycontrolsinmilitarypersonnelwithPTSD
Oneofthemostimportantfunctionsofnorepinephrineisits
roleasthe neurotransmitter releasedfromthe sympathetic
neurons affectingtheheart.
Anincreaseinnorepinephrinefromthesympatheticnervous
systemincreasestherateofcontractions.
Asa stresshormone,norepinephrineaffectspartsofthebrain,
suchasthe amygdala,where attention andresponsesare
controlled.
Alongwith epinephrine,norepinephrinealsounderlies
the fightorflightresponse,directlyincreasing heartrate,
triggeringthereleaseof glucosefromenergystores,and
increasingbloodflowto skeletalmuscle.Itincreasesthe
brain'soxygensupply.
Norepinephrinecanalsosuppressneuroinflammation when
releaseddiffuselyinthebrainfromthe locusceruleus.
Individualswiththisdisorderappeartodisplay
abnormalitiesindifferentmeasuresofNEalong
withhypersensitiveadrenergicreceptors
suggestiveofanoverallenhancednoradrenergic
state.Theproposedneuralcircuitryimplicatedin
PTSDisalsoinfluencedbythesecatecholaminergic
alterations.IncreasedNAmaycontributenotonly
totheenhancedfearacquisitionandconditioning
responsesbytheamygdala,butalsotolossof
prefrontalcontrolovertheamygdalathus
impairingextinctionofthefearresponse.
Studiesofglucocorticoids (GCs)andmemoryhave
revealedthatduringacutestress,elevatedGClevels
workinconcertwithnoradrenergicactivationto
enhancetheprocessofencodingandconsolidating
emotionalmemories(Rozendaal etal.,2006).
Onemodelthathasbeenputforthhypothesizesthat
themPFC whichnormallyhasinhibitorycontrolover
thenoradrenergicneuronsoftheLCandovertheHPA
axis,isrenderedineffectiveattimesofacutestress
thuspermittingenhancedstimulationofthe
amygdalabyGCsandNE,whichinturnenhances
encodingandconsolidationofthetraumaticmemory
(Hurlemann,2008).
Adrenergicreceptorsinindividualswithchronic
PTSDareparticularlysensitivetostimulationand
pronetohyperactivity.
10/5/2012
10
SerotoninmodulatesHPAaxisandLongtermtreatment
withSSRIappearstodecreaseHPAresponsivenessat
thepituitarylevel
JNeuroendocrinol. 1999Jun;11(6):46571.
Acuteandlongtermtreatmentswiththeselective
serotoninreuptakeinhibitorcitaloprammodulatethe
HPAaxisactivityatdifferentlevelsinmalerats.
JensenJB,JessopDS,Harbuz MS,Mrk A,SnchezC,
Mikkelsen JD.
Source:DepartmentofClinicalBiochemistry,
Bispebjerg Hospital,Copenhagen,Denmark.
jej@lundbeck.com
Incontrasttotheenhancingeffectsonencoding,
similarlyelevatedGClevelsmayimpairdelayed
memoryretrieval,particularlyforemotionally
arousingmaterial(Buchananetal.,2006),againin
thecontextofnoradrenergicactivationwithinthe
BLA.AninvertedUshapedcurvehasthusbeen
proposedtoexplainhowmemoryretrievalis
affectedbycortisolconcentrations(Wolf,2008)
andthisinturnmayexplainwhyindividualswith
PTSDhavedifficultysubsequentlyremembering
certainaspectsofthetrauma.
PrimaryexcitatoryneurotransmitterintheCNS
PlayaroleinthepathophysiologyofPTSDinpartviaitsactions
ontheHPAaxis
ViathemodulationofCRHreleaseinresponsetostress
Changesinglutamatelevelsplayakeyroleininitiationand
maintenanceoftheHPAresponse.
Hyperglutamatergic statemaybeimplicatedinPTSD
Isalsothoughttoplayafundamentalroleinmemoryformation,
(akeyprocessofPTSD).
Followingtraumaticevents,elevatedglutamatelevelsmayserve
toencodeandconsolidatetraumaticmemories,butalso
enhancehippocampaldamage(Joca etal.,2007).
PhasesofAdrenalDysfunction
10/5/2012
11
Stimulatesfatdepositsandcanresultinweightgain.
Increasedfataccumulationaroundwaist.
Increasesbloodpressure.
Increasesproteinbreakdownthatcanleadtomuscle
loss.
Causesdemineralizationofbonethatcanleadto
osteoporosis.
Interfereswithskin'sabilitytoregenerationandheal.
Causesdemineralizationofbonethatcanleadto
osteoporosis.
Interfereswithskin'sabilitytoregenerationandheal.
Cortisolisapowerfulantiinflammatoryagent.
SalivaryAdrenalProfile
BasicNeurotransmitters
Thyroidfunctiontests
BasalBodytemps
Beforebeginninganytreatmentprotocolonthe
adrenalglandsaclinicalhistoryshouldbetaken
andtestingshouldbedone.
1. Saliva
2. Serum
3. Urine
10/5/2012
12
DiurnalCortisol=4Cortisols(AM,Noon,Eve,
PM)
30minutes(afterawakening)
Beforelunch
Beforedinner
Beforebedtime(preferablyatleastonehourafter
dinner).
DHEA(NOTDHEAS)
*Totaloffivehormonetests
Labrix ClinicalServices ETL,2008
Cortisol Awakening Response
0
5
10
15
20
25
0 15 30 45 60 75
Time post awakening (minut es)
C
o
r
t
i
s
o
l

(
n
m
o
l
/
L
)
SalivaryCortisol:ABetterMeasureofAdrenalCorticalFunction
ThanSerum.ViningRF,etal.AnnClinBiochem (1983)20:329
35.
VenipunctureCausesRapidRiseinPlasmaACTH.Meeran Ketal.
BrJClinPract (1993)47(5):2467.
SalivaryCortisol AnAlternativetoSerumCortisol
DeterminationsinDynamicFunctionTests.AardalErikssonE,et
al.ClinChem LabMed(1998)36(4):215222.
HormoneProfilesinHumansExperiencingMilitarySurvival
Training.MorganCA,etal.BiolPsychiatry(2000)47:891901.
SalivaryCortisolDeterminedbyEnzymeImmunoassayis
PreferabletoSerumTotalCortisolforAssessmentofDynamic
HypothalamicPituitaryAdrenalAxisActivity.Gozansky WS,et
al.ClinEndocrin (2005)63:336341.
Urine
13hoursafterrising(not1
st
morningvoid)
Serotonin,norepinephrine,epinephrine,
dopamine,glutamate,GABA
Received7June2010Receivedinrevisedform21July2010Accepted30July2010
ReviewNeurotransmittersexcretedintheurineasbiomarkersofnervoussystemactivity:
Validityandclinicalapplicability
DavidT.Marc,JosephW.Ailts,DanielleC.AiltsCampeau,MichaelJ.Bull,KellyL.Olson
Hydrocortisone(physiologic
dosing)
DHEA
Melatonin
VitaminC
VitaminB5
VitaminB6
VitaminE
PhosphorylatedSerine
5 HTP
LTyrosine
LTheanine
Traceminerals
Zinc
Manganese
Selenium
Chromium
Molybdenum
Copper
Iodine
Rhodiola
Ashwagandha
Panax Ginseng
SiberianGinseng
Bioessays. 2008 Aug;30(8):74456.
Whatgoeson behind closed doors: physiological versuspharmacological steroid hormone actions.Simons SS Jr.
SteroidHormones Section, Bldg 10, Room8N307B, NIDDK/CEB, NIH, Bethesda, MD 208921772, USA.
Phase
0
Multivitamin/Multimineral
Omega3EFAs
VitaminD,IodineandProbiotics
10/5/2012
13
Phase
1
PhosphorylatedSerine100mgTIDorattimes
whenelevated
VitaminsB5(500mg)TID,B6(50mg)TID,C
(1000mg)TID
Melatonin(16mg)qhs ifcortisollevelselevatedat
night
DHEA*
Lifestylemodification:Deepbreathing,stress
management,exercise,optimaldietetc.
Phase
2
VitaminsB5(500mg)TID,B6(50mg)TID,C
(1000mg)TID
Adrenalglandularand/orherbaladaptogens in
morningandatnoon*
AminoAcids:5HTP,ltyrosine,ltheanine
Lifestylemodification:Deepbreathing,stress
management,exercise,optimaldietetc.
Phase3
VitaminsB5(500mg)TID,B6(50mg)TID,C(1000mg)
TID
Adrenalglandularand/orherbaladaptogens in
morningandatnoon.
hydrocortisonesupplementation510mginAMand
510mgatnoon
Melatonin
AminoAcids;5HTP,ltyrosine,ltheanine
Lifestylemodification:Deepbreathing,stress
management,exercise,optimaldietetc.
3options:
Rx
Compoundedcortisol
Glandularstandardized
glandular
Rx
Tabletsareavailablefororaladministrationin
threestrengths:eachtabletcontainseither
5mg,10mg,or20mgofcortisol.
Inactiveingredients:calciumstearate,corn
starch,lactose,mineraloil,sorbic acid,sucrose.
HOWSUPPLIED
Tabletsareavailableinthefollowing
strengthsandpackagesizes:
5mg(white,round,scored,imprintedCORTEF5)Bottlesof50
10mg(white,round,scored,imprintedCORTEF10)Bottlesof100
20mg(white,round,scored,imprintedCORTEF20)Bottlesof100
Rx
Cortisolcanbecompounded(intoanydoseyou
choose).
Especiallywhengivingthepatientdoses
differentthan5mg,10mgor20mg
Canhaveregularreleaseandsustainedrelease
blend
(70:30ratio 70%reg.cortisol:
30%slowreleaseagent)
10/5/2012
14
Sometimesstandardizedeachpelletcontains
2.45mg ofcortisol.
Otheringredientsinclude:driedadrenalcortex,
Echinacea,Prunus spp,Lomatium dissectum
root,lactoseandlactase.
SampleDosingSchedule
I.30minutesafterawakening:14pellets(2.57.5mgcortisol)
2.4hourslaterorbeforenoon:14pellets(2.57.5mgcortisol)
3.321(am7.5mg,noon5.0mg,midafternoon2.55.0mg)
glandular
Shorthalflife 8to12hours
1. Cortisone
2. Cortisol
Cortisolismetabolizedinmosttissues,but
primarilyinthelivertobiologicallyinactive
compounds.Thehalflifeofcortisolmaybe
prolongedinpatientswithhypothyroidism.
Inactivemetabolitesareexcretedbythe
kidneys.Negligibleamountsareexcretedinbile.
0.5mgofdexamethazone =15mgcortisol
Inadexamethazone suppressiontestusually1mgof
dex isgivenorally(i.e,30mgcortisol).
5mgprednisone=20mgcortisol
Anormalstartingdoseofprednisoneisbetween5
60mg/day.
MultipleSclerosistreatmentstartsat200mg/dayand
tapersto80mg/day.
Cortisol
(hydrocortisone)
Cortisone Prednisone
Dexamethasone
20mg 25mg 5mg 0.75mg
Lowdosephysiologicalcortisolsupplementationdoesnot
producesignsorsymptomsofglucocorticoidexcessand
hasnotbeenshowntocauseclinicallysignificant
adrenalsuppression.20mgoforalhydrocortisonehasfar
lessglucocorticoideffectonboneforexample,than5mg
ofprednisone(jodar 03)Studieshaveshownthat10mg
and40mgofhydrocortisone(theamountincreases
dependinguponbodyweight(Mah 2004)doesnotcause
boneloss,suppressionofimmunesystem,weightgain,
elevatedbloodsugar,elevatedbloodpressurethinning
skin,easybruisingorsuppressionofendogenouscortisol
production(Wichers 1999,McConnell2002,Danowski
1962,SafeUsesofCortisolbyWilliamMck JefferiesMD)
Hypothalamopituitaryadrenalaxisdysfunctioninchronic
fatiguesyndrome,andtheeffectsoflowdosehydrocortisone
therapy.
evidencesupportspreviousfindingsofimpairedadrenalcortical
responsivity inCFS.
lowdosehydrocortisonesupplementationisabletoincreasetheoverall
cortisolthroughput,suggestingthatthereisnot(over28d)a
compensatoryswitchingoffofendogenouscortisolproduction.
thosewhorespondedtotreatment,hadasignificantdecreaseinfatigue
ascomparedtonormalpopulationlevels,therewasacorresponding
normalizationofthebluntedcortisolresponsetohCRH challenge.
1. JClinEndocrinolMetab. 2001Aug;86(8):35455 leareAJ,Miell
J,HeapE,Sookdeo S,YoungL,Malhi GS,O'Keane V.
2. Jefferies,WilliamMcK.MD.SafeUsesofCortisol3rdedition
CharlesCThomasPublisher.LTD.ISBN0398075018
3. ThelowdoseACTHtestinchronicfatiguesyndromeandin
healthLucindaV.Scott1,SamiMedbak2,TimothyG.Dinan3
Articlefirstpublishedonline:4JAN2002DOI: 10.1046/j.1365
2265.1998.00418.xClinicalEndocrinologyVolume48,Issue6,
pages733737,June1998
4. LowDoseHydrocortisoneforTreatmentofChronicFatigue
SyndromeARandomizedControlledTrial
RobinMcKenzie,MD;AnnOFallon,RN;JanetDale,RN,MPH;
MarkDemitrack,MD;Geetika Sharma,MD;Maria Deloria;
DiegoGarciaBorreguero,MD;WilliamBlackwelder,PhD;
StephenE.Straus,MD
10/5/2012
15
TheamountofDHEAneededtobringamale
withAddisonsdiseaseintonormalphysiological
rangeis5070mg(Huntetal.2000).
Ifyouarefollowingphysiological(not
replacement)dosesyouwouldlikelynot
exceed:
Males2550mg/day
Females1025mg/day
Improvementinmoodandfatigueafterdehydroepiandrosterone replacementinAddison's
diseaseinarandomized,doubleblindtrial. Hunt PJ,etal.JClinEndocrinolMetab. 2000
Dec;85(12):46506.
Secretedbythepinealgland
Regulatescircadianrhythmandinducesleep.
Cushing'ssyndromewasshowntohave
significantlylowerlevelscomparedtohealthy
controlgroups.
Studiesalsohaveshownthatnightly
administrationof2mgofmelatoninhave
supportedadrenalrecoveryafter6monthsof
administration
(Soszynskietal.1989;Brulsetal.2000;Pawlikowski
etal.2002).
Ofallthevitaminsandmineralsinvolvedinadrenalmetabolism,
vitaminCisprobablythemostimportant.Infact,themore
cortisolmade,themorevitaminCused.VitaminCisso
essentialtotheadrenalhormonecascadeandthemanufacture
ofadrenalsteroidhormones1
StudiesshowthatvitaminCcanattenuateandinfluence
cortisol,inducinganantiinflammatoryresponsetoprolonged
exerciseandstress.VitaminChasbeenshowntoreducethe
elevationofcortisolinresponsetoheavyexercise.Inhuman
studies,3000mgofvitaminCdailymitigatedariseinblood
pressure,cortisol,andsubjectiveresponsetoacute
psychologicalstress
1)Dr.JamesL.WilsonistheauthorofAdrenalFatigue:The21stCentury
StressSyndrome.In1998
2)DiLuigietal.2001;Petersetal.2001a,2001b;Brodyetal.2002).
(CoA)thebasisfortheproductionof
hemoglobin,bile,sexandadrenalsteroids,
cholesterol,andotherbrainchemicalsand
neurotransmitters.
Pantothenicaciddeficiencyresultsinadrenal
insufficiency,whichischaracterizedbyfatigue,
headache,sleepdisturbances,nausea,and
abdominaldiscomfort
PantothenicAcidAndPantethine,MichaelLam,MD,MPH(Tarasovetal.1985;Smith
etal.1996;Murrayetal.1997).
B6(pyridoxine) isalsoacoenzymeinseveralof
thebiochemicalpathwaysintheadrenalcascade
andplaysaroleinthefunctioningofthe
hypothalamic/pituitary/adrenal(HPA)axisthat
modulatesadrenalactivityandthestress
response.
JamesWilsonwebsite2010
Absorbsandneutralizesthesedamagingfree
radicalmoleculesinsidetheadrenalglands
(VitaminCenhancesvitaminEsactivityinside
thecellbyregeneratingthecapacityofvitamin
Etosequesterthefreeradicals).
WorkshandinhandwithVit.Ctokeepthe
adrenalcascadefunctioning.
HighamountsofvitaminEarenecessaryin
orderfortheadrenalstomaintainhighlevelsof
steroidproductionandrecoveradequately.
Bieri,JG; Evarts (1974)."Tocopherol: metabolism,biologicalactivityandsignificanceinhumanvitaminE
nutrition". AmericanJournalofClinicalNutrition 27 (9): 980986. PMID 4472121
10/5/2012
16
SevenForestsSanQi17(26tablets)
StJohnss Wort (300mg)
5HTP(100mg*)
LTheanine (50200mg)
Melatonin16*mg
Chamomile,ValerianRoot(asdirected)
Normalizeyoursleep
Sleepmore
Sleepattherighttimes(lightdarkcircadian
rhythms)
Sleeplater(until8:30or9am)
Balancehormones;adrenalsand
estrogen/progesterone
Book:LightsOut
Takenonemptystomach30minutesawayfrom
food
Crossthebloodbrainbarrierandinteractwith
HPAaxisandneurotransmitterregulation
Themonoamineneurotransmittersserotonin,dopamine,norepinephrine,
andepinephrinedonotcrossthebloodbrainbarrier;therefore,
peripheraladministrationoftheseneurotransmitterswillnot
increasecentralnervoussystemneurotransmitterlevels.Theaminoacid
precursorsoftheseneurotransmittersdocrossthebloodbrainbarrier.
Theonlywaytoincreasecentralnervoussystemneurotransmitterlevelsis
throughadministrationofaminoacid
Precursors.
MartyHinz MD FoodandNutritionindiseaseManagement, Ch 29,pp465483
Birdsall TC. 5Hydroxytryptophan: a clinicallyeffectiveserotoninprecursor. Altern MedRev. 1998Aug; 3(4):271280.
PyleAC,Argyropoulos SV,Nutt DJ. Theroleofserotonininpanic: evidencefromtryptophandepletionstudies. Acta
Neuropsychiatrica 2004; 16:7984
Aphospholipid thatisastructuralcomponent
ofthebiologicalmembranesinanimalsand
plants.
BluntstheHPAsensitivitybyalteringACTHand
cortisol responses
(Monteleoneetal.1990;Kelly 1999;Bentonetal.2001).
Alsoknownasoxitriptan
Anaturallyoccurringaminoacid
Chemicalprecursoraswellasmetabolic
intermediateinthebiosynthesisofthe
serotoninandmelatoninfromtrytophan
Chronicstressalsoactsinthebraintodecrease
serotonin.Serotoninactsinthebrainto
enhancetheeffectsofleptin inthe
hypothalamus.
Adv Exp MedBiol. 1996;398:3739.Fibromyalgiaandmigraine,twofacesofthe
samemechanism.Serotoninasthecommonclueforpathogenesisandtherapy.
Nicolodi M,Sicuteri F.Interuniversity CentreofNeurochemistry,
UniversityUnit,Florence,Italy.
Notconsideredanessentialaminoacidbecause
thebodycansynthesizethisfromphenylalanine
Convertedintodopamineandnorepinephrine
Underepisodesofstress,thebodymaynot
havethecapacitytoproduceenoughtyrosine
fromphenylalanine;therefore,supplementation
supportshormoneandNTproduction
Increasesalertnessandmentalclarity
IntJGenMed2011 Hinz etal, publisherandlicenseeDoveMedical Press Ltd.
Aminoacidmanagement ofParkinsons disease:acasestudy
Marty Hinz,
1
AlvinStein,
2
andThomas Uncini
3
1
Clinical Research, NeuroResearch Clinics, Inc., CapeCoral, FL, USA;
2
SteinOrthopedic Associates, Plantation, FL, USA;
3
DBS Labs, Duluth, MN, USA
Correspondence:Marty Hinz, 1008 DolphinDr, CapeCoral, FL 33904, USA, Tel +1 218 626 2220, Fax+1 218 626 1638, Email
marty@hinzmd.com
10/5/2012
17
Glutamicacidanalogderivative
Aminoacidfoundingreentea
Producesacalmingeffectinthebrain.
Increasinggammaaminobutyric acid(GABA)(relaxer
andcreatesasenseofwellbeing).
Helpmodulatemood
Reducementalandphysical
Improvescognition
Abeetal.1995;Kobayashi etal.1998;Juneja etal.1999
GomezRamirez M;Higgins, BA;Rycroft, JA;Owen, GN;Mahoney, J;Shpaner, M;Foxe, JJ(2007).
"TheDeployment ofIntersensory SelectiveAttention:AHighdensity Electrical Mapping StudyoftheEffects of
Theanine".ClinNeuropharmacol 30 (1):2538.KimuraK, Ozeki M, Juneja L, Ohira H(2007).
"LTheanine reduces psychological andphysiological stress responses".Biol Psychol 74 (1):39
45.doi:10.1016/j.biopsycho.2006.06.006.PMID 16930802.
Haskell CF, Kennedy DO, MilneAL, Wesnes KA, Scholey AB(2008).
"Theeffects ofltheanine, caffeineandtheircombination on cognition andmood".Biol Psychol 77 (2):11322
Antioxidantactivity
Liverprotectionandantitoxin
activity
Improvedbloodsugar
metabolism
Lesscravingforalcoholor
sugar
Improvedimmuneresistance
Increasedenergyandstamina
Improvedmuscletone
Increasedstrength
Fasterrecovery
Betterfocusand
concentration
Lessanxiety
Bettersleep
Bettermotivationand
productivity
Afeelingofwellbeing
Bettermoods
Haveanormalizingeffectonthebodyandtobecapable
ofeithertoningdownorstrengtheningtheactivityof
hyperandhypofunctioningsystems.
Themechanismoftheantistressor
adaptogenic activitiesofradixeleutherococci
appearstobethreefold.
Extractsoftherootshaveanadaptogenic effect
thatproducesanonspecificincreaseinthebodys
defenseagainstexogenousstressfactorsand
noxiouschemicals.
Therootsalsostimulatetheimmunesystem
Andpromoteanoverallimprovementinphysical
andmentalperformance."
AdaptogensthatHelpwithAdrenalFatigue:GetGoingAgainwithNaturalHerbalRemedies
http://www.suite101.com/content/adaptogensthathelpwithadrenalfatiguea162757#ixzz1EWWOrDIz
Alargestudyreviewedtheresultsofanumberofclinical
trialsinvolving2,100healthymenandwomenages19to
72.Subjectsweregivendosesofginsengrangingfrom2
to16mloffluidextract,33percentethanol,fromoneto
threetimesdailyforupto60days.Subjectshad
increasedmentalalertnessandworkoutput,enhanced
athleticperformanceandimprovedworkquality.They
alsoexhibitedanimprovedabilitytowithstandadverse
conditionssuchasheat,noise,increasesinworkloadand
physicalexertion.
BullWorldHealthOrgan.1985;63(6):965981.
Medicinalplantsintherapy
*
NormanR.Farnsworth,Olayiwola Akerele,AudreyS.Bingel,
Djaja D.Soejarto,andZhengang Guo
Effectiveatimprovingaperson'sabilityto
withstandstress:
Improvedworkperformanceandquality
Enhancesmentalfunction
Increasesthereleaseofadrenocorticotropic
hormone(ACTH),whichstimulatesanincrease
inadrenalhormonesecretion.
Counteractstheshrinkageoftheadrenalgland
causedbycorticosteroiddrugs.
Murray, M. & Pizzorno,J. EncyclopediaofNaturalMedicine: 499. Rocklin,Calif.: Prima Publishing,1990.
Shibata,S.,et al. "Chemistryandpharmacologyofpanax," EconMed Plant Res,1: 21784,1985.
Immunomodulating
Modifiesanxietyandotherpsychological
complaints.
Whencortisolistoohigh,itlowersit,andifitis
toolow,itraisesit.
Upadhaya, L., et al."Roleof an indigenousdrug Geriforte on blood levelsof biogenicamines
and itssignificancein thetreatmentof anxiety neurosis," Acta Nerv Super, 32(1): 15,1990.
Ghosal, S., et al."Immunomodulatory and CNSeffectsof sitoindosides IXand X,twonew
glycowithanolides fromWithania somnifera," Phytother Res, 3(5):2016, 1989.
Bhattacharya, S.K., et al."Antistressactivity of sitoindosides VIIand VIII,
new acylsterylglycosides fromWithania somnifera," Phytother Res, 1(1):3237, 1987.
www.smartpublications.com.
Wilson, James. Adrenal Fatigue.
10/5/2012
18
Promotesorenhancesimmunesystemfunction
Stimulatestheadrenalcortex
Inhibitsthebreakdownofadrenalhormoneby
theliver,therebyincreasingcorticosteroidlevels
incirculation
Inhibitscortisol'sabilitytopromotethymus
atrophy
1ProtocolJournalof BotanicalMedicine,
1(4):194. Ayer, Mass.:HerbalResearch Publications,1996.
2)Murray, M. & Pizzorno,J.,op. cit.,pp. 60,61,67.
3)Armanini,D.,Kargbowiak, I.,etal. "Affinity of liquorice derivativesformineralocorticoid and glucocorticoid receptors,
" Clin Endocrinol,19: 60912, 1983.
Diminishesfatigue
Improvesattentionspan
Improvesmemory;
Makesworkersmoreproductive.
Increasesthecapacityformental/cognitive
work
Enhancespermeabilityofthebloodbrain
barriertodopamineandserotonin.
Rhodiola rosea in stress induced fatigue: a doubleblind crossover study of a standardized extractSHR5with a repeated lowdose
regimen on thementalperformanceof healthy physicians during nightduty.Darbinyan V,Kteyan A,Panossian A,Gabrielian E,Wikman
G,Wagner H.Department ofNeurology,ArmenianState MedicalUniversity Phytomedicine 2000;7(5):36571.
Usetryptophanif5HTPiscausingGIupset
Balancing:neurotransmitters,sexhormonesand
adrenalfunctionareallinterdependentand
correctingonepositivelyaffectstheother
Nodirectfeedbackbetweenzona fasciculata and
zona reticularistreateachzoneasifseparate
gland
Treatthepathwayaswellasthelevel
TreatHPAdysfunctionfirstthenmayneedto
treathypoadrenia ifpresent
DHEA,melatoninand phosphoylated serinecan
beusedtoquietHPAdysfunction
ACTHisnotstimulatingincreasedandrogensin
womenwithMet.SyndromeandPCOS