HPA Axis Dysfuncon in Obesity - GDX
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HPA Axis Dysfunc.on in Obesity Melanie Dorion, AGNP The views and opinions expressed herein are solely those of the presenter and do not necessarily represent those of Genova Diagnos=cs. Thus, Genova Diagnos=cs does not accept liability for consequences of any ac=ons taken on the basis of the informa=on provided.
Transcript of HPA Axis Dysfuncon in Obesity - GDX
HPAAxisDysfunc.oninObesityMelanieDorion,AGNP
TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos=cs.Thus,GenovaDiagnos=csdoesnotacceptliabilityforconsequencesofanyac=onstakenonthebasisoftheinforma=onprovided.
MichaelChapman,NDMedicalEduca.onSpecialist-Asheville
MelanieDorion,AGNP
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HPAAxisDysfunc.oninObesityMelanieDorion,AGNP
TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos=cs.Thus,GenovaDiagnos=csdoesnotacceptliabilityforconsequencesofanyac=onstakenonthebasisoftheinforma=onprovided.
• Reviewcontribu=ngfactorsinweightgain• DiscussresearchonHPAaxisdysfunc=oninobesity• DiscussothercausesofHPAaxisdysfunc=on• Introducetherapeu=cop=onsfocusingonadrenalsupport
Objec.ves
ObesityandWeightGainAreMul.factorial!!!• Dietandlifestyle• Hormonalinfluences
– Thyroid,Insulin,Cor=sol,Lep=n• Nutri=onaldeficiencies
– VitaminD,Omega-3faVyacids
• Immuneandgutdysbiosis• Gene=cs/epigene.cs• Neurobehavioral• ...
Contribu.ngFactorsinWeightGain
TheHormonalComponent
https://commons.wikimedia.org/wiki/File:HPA_Axis_Diagram_(Brian_M_Sweis_2012).png
Hypothalamic-Pituitary-Adrenal (HPA) Axis
Mul.pleStudiesHaveLookedatThis-Conflic.ngResults!• SomeshowgreaterACTHresponsesothersnot• Circula=ngcor=sollevelsnotconsistentlyelevated• Lowmorningcor=solbuthighurinarycor=sol• Possibleexplana=ons
– smallsamplesizes,– singlegenderandsingleethnicity– =ssuespecificaltera=onsincor=solmetabolism
(onlyproperlytestedbyadipose=ssuebiopsy=NOTprac=cal)
HPAAxisandObesity
GeneralPaQerns• GreaterabdominalfatisassociatedwithgreaterresponsivityoftheHPAaxis• Upregula=onofcor=soloutputinadipocytes
– duetogreaterexpressionof11β-hydroxysteroiddehydrogenasetype1(11β-HSD1)• Downregula=onofcor=solinhepa=c=ssue• “OverallBMIappearstoalsoberelatedtoahyper-responsiveHPAaxisinmany
butnotallstudies,suchaswhenacutereac=vityisexamined.”(Rodriguez,2015)
WhatisReallyHappening??
HPAAxis-Adrenals
Lucassen A. & Cizza G. Curr Obes Rep. 2012 December ; 1(4): 208–215.
UrinarylevelsofTHF(tetrahydrocor=sol)andTHE(tetrahydrocor=sone)areusuallyincreasedinobesesubjects.
• IncreasedHSD1ac=vityinadipose=ssueanddecreasedinhepa=c=ssue• IncreasedurinaryTHEindicatesincreasedcatabolismofcor=sol=
increasedcor=solclearance• Hyper-responsiveHPAaxisinobesitybutlessresponsivetosuppression
tests(dexamethasonesuppressiontest)• Hyperac=veSNSincentralobesity• Weightlossleadsto
– DecreasedHSD1ac=vity– Decrease5α-reductaseac=vity
TakeHomePointsfromLucassen&Cizza
“HigherBMIandWCareassociatedwithneuroendocrinedysregula.on[…].”
Champaneri S., et. al. Obesity (Silver Spring). 2013 Jan;21(1):E56-63.
MESA
Study
• Fortheen.recohort,bothBMIandWCwerenega.velycorrelatedwithawakeningcor.sol
• THM(tetrahydrometabolites)andTHE(tetrahydrocor=sone)posi=velycorrelatedwithBMIandWC
• Amongpar=cipantswithDM:– Cor=solcurveparameterssugges=veofhigherHPAaxisac=vity– Dysfunc=onwereassociatedwithhigherHbA1c
MESAStudyOutcomes
• Chronicstress–physicaloremo=onal• Sleepdisorders
– Notonlydoesobesitycontributetosleepproblems,butsleepproblemscanalsocontributetoobesity–chickenortheegg??
– Inadults,OSAises=matedtobeashighas45%inobesesubjects=es=mated18millionAmericanshaveOSA–YIKES!
– Poorsleepandsleepdepriva=ondecreasesglucosetolerance,decreaseslep=n,increasescor=solandmayincreaseappe=te
• Inflamma=on(IL-6upregulatesHSD1expression)• Mooddisorders• Lowcaloriediets• Thyroiddisorder
OtherCausesofHPAAxisDysfunc.on
“Restric.ngcaloriesincreasedthetotaloutputofcor.sol,andmonitoringcaloriesincreasedperceivedstress”
Rela.onshipbetweenAdrenals&Thyroid
FactorsThatAffectThyroidFunc.on
HPAAxisTes.ng
Source: Genova Diagnostics
WhatTesttoOrder?
Serum?
Saliva?
Urine?
http://www.townsendletter.com/Jan2014/hormone0114.html
24HourUrinePanels
• Alwaysincludecor=sol!• Measuresunboundhormone
reflec=ngbioavailableforms• Allowmetabolitestobeevaluated• Accountforthefulldayandnight
ofhormonalsecre=on–removesfalsehighs/lowsd/tcircumstances
• Lowmineralocor=coidsareaclearindicatorofchronicHPAaxisdysfunc=on
SalivaryTes.ng
• 4samples• Measuresfreehormone• Diurnalcurve• DHEAmeasurement
• Sleepdisorders– Notonlydoesobesitycontributetosleepproblems,
butsleepproblemscanalsocontributetoobesity–chickenortheegg??
– Inadults,OSAises=matedtobe~25%,andashighas45%inobesesubjects=es=mated18millionAmericansOSA–YIKES!
– Poorsleepandsleepdepriva=ondecreasesglucosetolerance,decreaseslep=n,increasescor=solandmayincreaseappe=te
– RLS• Mooddisorders
OtherCausesofHPAAxisDysfunc.on
1318_5148227
Diurnalsalivarycor.solisassociatedwithbodymassindexandwaistcircumference
Champaneri S., et. al. Obesity (Silver Spring). 2013 Jan;21(1):E56-63.
• EpworthandBerlinscreenings
ScreeningandTes.ngforSleepandMoodDisorders
http://sleepapnea.org/wp-content/uploads/2017/02/ESS-PDF-1990-97.pdf
• BeckDepressionScale,PHQ-2,PHQ-9
ScreeningandTes.ngforSleepandMoodDisorders
http://www.hr.ucdavis.edu/asap/pdf_files/Beck_Depression_Inventory.pdf
ThyroidTes.ngLookforOp.malLevels,notSimply“Normal”
• TSH<2.5• FT4>1.3• FT3>3.0• rT3<20
ReverseT3• OccupiessamereceptorsitesasFT3• Increasedin:
– Mitochondrialdysfunc=on(InsulinResistance,DM,Lyme,fibro,etc.)– Elevatedcor=sol– SeandFedeficiencies(wantferri=n>50)
Management
AlwaysStartwithDietandLifestyle!
• Carbohydrateconscious:aboutor<120gofnetcarbs/day• Lowcarbohydrate:<100gofnetcarbs/day• Ketogenic:<60-40gofnetcarbs/day
Netcarbs:(totalcarbohydrate–fiber)Readthefoodlabels!
DietaryRecommenda.ons:LowerCarbohydrate,ModerateProteinandHigherFat
Management
• Lifestyle– Improvesleep!Orrefertosleepspecialist
– Movementandexercise– Deepbreathingandmindfulnessdaily– Daylightexposurefirstthinginthemorningandthroughouttheday
• “Tiredandwired”pa=ent– Phospha=dylserineinarernoon&qHS– GABA:200-250mgor125mgsublingual– Homeopathics(EX:CalmsForte)
• Others– Magnesium– P5P
Management
Mind/BodyTherapies• HeartRateVariability(HRV),
morningHR• HeartMath• Medita=on/prayer• Cogni=veBehavioralTherapy,
EFT,etc• MovementTherapies
(Yoga,TaiChi,QiGong)Reproduced from http://alessandroferretti.co.uk/
• Adaptogens– Ashwagandha(Withaniasomnifera)– Rhodiola(Rhodiolarosea)– Schisandra(Schisandrachinensis)– Asianginseng(Panax)– Siberianginseng/Eleuthro(Eleutroccocussen=cosus)
• Cau=oninpa=entswithanxiety
• Nervines– Oats(Avenasa5va)– Gotukola(Centellaasia5ca)
• Others– Woodbetony(Stachysoff.):=n½-1dropperTID
BotanicalSupport
Image: Creative Commons
• Licoriceandturmericandgreentea,OhMy!
Management-11β-HSD1Inhibitors
JSteroidBiochemMolBiol.2009Feb;113(3-5):248-52.PLoSOne.2014Jan3;9(1):e84468.
• Licoriceandturmericandgreentea,OhMy!• Salicylate
Management-11β-HSD1Inhibitors
Diabetes.2012 Apr;61(4):790-6. https://www.ncbi.nlm.nih.gov/pubmed/22357964
Significantproblem!51%ofU.S.adults>65yohavepre-dm• Insulinpromoteslipogenesisandpreventslipolysis
– Elevatedinsulin(insulinresistance)=difficultfatloss!• Berberine:1-2000mg/dindivideddoseswithfood• Chromium:1-2000mcg/dindivideddoseswithfood• Cinnamon:1-6g/dayindivideddoses
InsulinResistance
The American Journal of Medicine, 2008;121:519-524 N Engl J Med 2005;353:1454-62.
http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
Case1
70YOFemalePresentsforWeightManagementandFa.gue
• 6+yearsofdebilita=ngfa=gueandongoingconsistentslowweightgain• Hasseenmanytradi=onalandintegra=veprovidersw/omuchrelief• Currentsymptoms:GI(bloa=ng,cramping,diarrhea),fa=gue,brainfog,
memoryissues,mmweakness,stress/anxiety• PastHistory:etohabuse,Lymedisease,OSA,lowFe• BMI30,othervitalswnl• Labs
– Nutri=onalandhormonalpanels– Reac=vatedmono– ++Celiacgene=cs– ElevatedANA– Otherlabswnl
CaseHistory
• IMhydroxoB12andoralBsinclP5P• Con=nueweeklyhighCIVswithmagnesiumandglutathionepush• Herbaladaptogeniccomboinam• GutsupportandGlutenfreeandlowercarbdiet–nomorenightlyTriscuits!!!
– discussedKetogenicdiet–maynotbeappropriaterightnowgiventheexhaus=on• Dailygentleexercisewitheitherpilates,yogaorwalking/hiking• Deepbreathing/medita=ondaily–ateveryredlightforexample• FasterEFTwithaprac==oner
Management
• Atthetwoweekfollow-up,pa=entreportsfeelingmoreenergythanhasinyears
• Atthefourweekfollow-up,shecon=nuestofeelbeVerandweightgainhasstopped
Follow-up
285_2731421
Case218YOFemalePresentsforWeightManagementandSleepIssues
• 3+yearswithsteadyweightgain,sleepissues(hardtofallasleepandfrequentwakings)andfa=gue/focusisues
• Meds:Lexapro,TrazodoneqHS,Adderall,Synthroid• Supplements:mul=,Bcomplex,melatoninqHS• Diet:StandardAmericanDiet(SAD)• Exercise:none• Vitals:BMI33,othervitalswnl• Labs
– Thyroid:lowfT3,sub-op=malfT4– Pre-dmA1c5.7– Otherslabswnl
CaseHistory
• Changeindiet:lowcarb,lowgrain,glutenfree,cutsugars• Sleephygiene• TaperofftheTrazodone,startmagnesiumqHS• Stopcurrentpharmacybrandmul=andBcomplex,startMitoCoreandberberine• StopSynthroidandswitchtoNatureThroidandslightincreaseindose• Walk15-30min3-4x/wk
Management
• Vitals:weightisup,othervitalswnl• OffTrazodone,easiertofallasleepbuts=llwaking,s=llusingmelatonin• FeelsslightlybeVerinthemorning,easiertogetup• Walkingafewdaysperweekandconsideringjoiningthelocalgym
• Ordersalivarycor=sol
6WeekFollow-Up
• FurtherdiscussionintoHx– Moldexposure,s=lllivesinthesamehouse,nomoldremedia=on– Sharesbedroomw/hersisterwhosnoresandsleepswithanightlight
• Management– Gethometestedformold– Sleepinanotherroomorlosethenightlight– Adrenalsupportcombo– AddCor=solManagerqHS– Integratemedita=on/guidedmedita=onbeforebed
Follow-UpandManagement
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TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos=cs.Thus,GenovaDiagnos=csdoesnotacceptliabilityforconsequencesofanyac=onstakenonthebasisoftheinforma=onprovided.
TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos=cs.Thus,GenovaDiagnos=csdoesnotacceptliabilityforconsequencesofanyac=onstakenonthebasisoftheinforma=onprovided.
HPAAxisDysfunc.oninObesityMelanieDorion,AGNP
TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos=cs.Thus,GenovaDiagnos=csdoesnotacceptliabilityforconsequencesofanyac=onstakenonthebasisoftheinforma=onprovided.
