insulin resistance solution

www.InsulinResistanceCure.com

1

The Insulin Resistance Solution

CopyrightMartinMalmberg.Nopartofthisdocumentmaybereproduced,inwholeorinpart,byanymeans,electronicormechanical,includingphotocopying,recordingorbyaninformationstorageandretrievalsystem,withoutwrittenpermissionfromtheauthor.Allrightsreserved.


2

MedicalDisclaimerTheauthorandpublisherofthisdocumentandtheaccompanyingmaterialshaveusedtheirbesteffortsinpreparingthisdocument.Theauthorandpublishermakenorepresentationorwarrantieswithrespecttotheaccuracy,applicability,fitness,orcompletenessofthecontentsofthisdocument.TheinformationcontainedinthisEbookisstrictlyforeducationalpurposes.Therefore,ifyouwishtoapplyideascontainedinthisEbook,youaretakingfullresponsibilityforyouractions.Theauthorandpublisherarenotlicensedmedicaldoctorsandarenotprovidingmedicaladvice,ordiagnosingortreatinganyconditionyoumayhave.Alwaysconsultwithyourphysicianaboutyourpersonalhealth,medical,insulin,anddiabetesrelatedissues.Thecontentsofthisbookarepresentedforinformationpurposesonlyandarenotintendedasmedicaladvice,nortoreplacetheadviceofamedicaldoctororotherhealthcareprofessional.Anyonewishingtoembarkonanydietary,drug,exerciseorlifestylechangeforthepurposeofpreventingortreatingadiseaseorhealthconditionshouldfirstconsultwith,andseekclearanceandguidancefrom,acompetenthealthcareprofessional.Theinformationinthisbookshouldnotbeconstruedasspecificadvice;itisalimitedreviewoftheavailablescientificandempiricalevidence.Itispresentedforthesolepurposeofstimulatingawarenessandfurtherinvestigationofimportantinformationthatmayhelpthereaderachievebetterhealth.Anyindividualwishingtoapplytheinformationinthisbookforthepurposesofimprovingtheirownhealthshouldnotdosowithoutfirstreviewingthescientificreferencescitedandconsultingwithaqualifiedmedicalpractitioner.Allpatientsneedtobetreatedinanindividualmannerbytheirpersonalmedicaladvisors.Thedecisiontoutilizeanyinformationinthisbookisultimatelyatthesolediscretionofthereader,whoassumesfullresponsibilityforanyandallconsequencesarisingfromsuchadecision.Theauthorandhiscompanyshallremainfreeofanyfault,liabilityorresponsibilityforanylossorharm,whetherrealorperceived,resultingfromtheuseofinformationinthisbook.OurstatementshavenotbeenevaluatedbytheUSFoodandDrugAdministrationandthisbookandreferencedproductsarenotintendedtodiagnose,treat,cureorpreventanydisease.

FinancialDisclosureThisbookcontainsaffiliatelinks,andtheauthormaybecompensatedforpurchasesyoumakeonsubsequentwebsites.TheauthorwillbecompensatedifyouusehisdiscountcodewhenplacingyourfirstorderasanewcustomeroniHerb.com.


3

Table of Contents Foreword .................................................................................................................................... 6 Introduction................................................................................................................................ 8 Whatisinsulinresistance?..................................................................................................... 8 Howdoesinsulinresistanceleadtodisease?........................................................................ 9 Insulinresistancecanleadtohighbloodsugar,too(prediabetes,type2diabetes) .......... 10 Whatarethedangersofhighbloodsugar?......................................................................... 11 Insulinsensitiveorinsulinresistant?Thatsthequestion ................................................ 12 Howtodiagnoseinsulinresistanceandtrackprogress....................................................... 13 Howtogetthemostoutofthisbook .................................................................................. 16

Chapter1BodyFatandInsulinResistance .......................................................................... 17 BeyondBodyMassIndex ..................................................................................................... 18 WaisttoHipRatio................................................................................................................ 19 Waistcircumference ............................................................................................................ 20 RedefiningobesityUnderstandingmetabolicobesity................................................... 21 Whatcausesacentralfatdistribution? ............................................................................... 23 Determiningifyouhaveexcessfat ...................................................................................... 23 Whattodoifyouhaveexcessfat(LOSEIT)......................................................................... 24 Cancentralfatbespecificallytargetedforfatloss?............................................................ 26 Canyouhavetoolittlebodyfat? ......................................................................................... 26 Fatlosstips ........................................................................................................................... 26 Summary .............................................................................................................................. 27

Chapter2IronandInsulinResistance.................................................................................. 29 Vegetarianshavelowerinsulinresistance........................................................................... 30 Blooddonorshavelowerinsulinresistance ........................................................................ 30 IronandIRareassociated,butdoesironreductionactuallyhelp? .................................... 31 Howdoesironcauseinsulinresistance? ............................................................................. 33 Whoshouldlowertheirironandhowlow? ........................................................................ 34 Ironreductionandothermarkersofhealth/disease .......................................................... 35 Howtoreduceironlevels .................................................................................................... 36 Lowironavailablediet..................................................................................................... 37 Whatkindofresultscanyouexpectfromsuchadietaryintervention?......................... 38 Exercise............................................................................................................................. 38 Phlebotomy(bloodletting) .............................................................................................. 39 Blooddonation................................................................................................................. 39 IP6.................................................................................................................................... 39 Puttingittogether ............................................................................................................ 40

Summary .............................................................................................................................. 40 Chapter3ExerciseandInsulinResistance ........................................................................... 42 Ishigherintensitybetterthanmoderateintensity?Iswalkinggoodenough?................... 44 Aerobicexercise,strengthtrainingorboth?Howoftenandhowmuch? .......................... 45 AwordaboutHIIT(a.k.a.HIIE) ............................................................................................. 46 Thenittygrittydetailsoftraining ........................................................................................ 47

Chapter4SupplementsAgainstInsulinResistance .............................................................. 51


4

Magnesium(Mg) .................................................................................................................. 51 Magnesiumsupplements ................................................................................................. 52

FoodsHighinMagnesiumper200calorieservingbycategory .......................................... 53 SelectCerealGrainsandPasta......................................................................................... 53 SelectVegetables ............................................................................................................. 53 SelectFruits ...................................................................................................................... 54 SelectSeedsandNuts ...................................................................................................... 54 FinfishandShellfish.......................................................................................................... 54 Beverages ......................................................................................................................... 54

Chromium............................................................................................................................. 54 VitaminK .............................................................................................................................. 55 VitaminD.............................................................................................................................. 56

Chapter5SleepandInsulinResistance................................................................................ 59 Background........................................................................................................................... 59 Studiesonsleepandinsulinresistance................................................................................ 60 Qualityofsleepmatters....................................................................................................... 62 Awordaboutsleepdisorderedbreathing ........................................................................... 63 Howdoesshortsleepcauseinsulinresistance? .................................................................. 64 Doeslongsleepcauseinsulinresistance? ........................................................................... 65 Howmuchshouldyousleep? .............................................................................................. 66 Howtosleepwell ................................................................................................................. 67 Summaryoffindings ............................................................................................................ 67

Chapter6DietandInsulinResistance.................................................................................. 69 Minimizinghighpostmealinsulinandbloodsugarlevelsbydiet ...................................... 71 DoIhavetoeatlowcarb? ................................................................................................... 74 Exerciseandcarbohydrates ................................................................................................. 75 Highcarb,highfiberdiets(HCFdiets) ................................................................................. 76 Howyoupreparefoodmatters............................................................................................ 79 Docarbohydratescauseinsulinresistance? ........................................................................ 79 GlycemicIndexandGlycemicLoad...................................................................................... 80 Dietaryfatsandinsulinresistance ....................................................................................... 80 Dairyandinsulinresistance ................................................................................................. 82 Doesfructosecauseinsulinresistance?Whyitdoesntmatter ....................................... 82 Awordaboutdarkchocolate............................................................................................... 84 Caffeine/coffeeandinsulinresistance................................................................................. 84 Additionaldiettips ............................................................................................................... 86 Puttingitalltogether ........................................................................................................... 87 Dietwheninsulinsensitive................................................................................................... 88 Goodcarbsourcesforahighcarbdiet ................................................................................ 89

AppendixA:WhatEveryInsulinResistantPersonShouldKnowAboutLosingWeight ......... 90 Introduction.......................................................................................................................... 90 NutritionBasicsUnderstandingCalories,Protein,Carbs,FatsandAlcohol ..................... 90 Calories ............................................................................................................................. 91 Protein .............................................................................................................................. 91 Carbohydrate.................................................................................................................... 91 Fat..................................................................................................................................... 92 Alcohol(a.k.a.ethanol) .................................................................................................... 92


5

TheDifferenceBetweenPercentageofWeightandPercentageofEnergy.................... 92 InsulinResistantIndividualsDoNotHaveAHarderTimeLosingFat .................................. 94 OnlyCaloriesCountSoCountCalories.............................................................................. 94 HowToDetermineYourTotalDailyEnergyExpenditure .................................................... 95 HowToDetermineYourBodyFatPercentage ................................................................ 96 TotalDailyEnergyExpenditure=BMRxActivityFactor.................................................. 97

HowManyCaloriesShouldIEatPerDay? ........................................................................... 98 DeterminingYourMacronutrients(Proteins,Carbs&Fats)................................................ 99 HowmuchproteinshouldIeat?.................................................................................... 100 HowmuchcarbohydrateshouldIeat? .......................................................................... 100 HowmuchfatshouldIeat? ........................................................................................... 101 Anexample..................................................................................................................... 101 HowmuchalcoholshouldIconsume?........................................................................... 102 Awordaboutmacronutrientratios ............................................................................... 103

WhichFoodsToFocusOn .................................................................................................. 103 Proteinrichfoods........................................................................................................... 103 Carbohydraterichfoods ................................................................................................ 104 Carbohydraterichsmallamounts............................................................................... 104 Fats ................................................................................................................................. 104 Alcohol............................................................................................................................ 105

WhichFoodsToLimit ......................................................................................................... 105 AWordAboutIronReduction............................................................................................ 106 UnderstandingtheIIFYMPhilosophy................................................................................. 106 ConstructingYourDiet ....................................................................................................... 106 AreThereAlternativesToCalorieCounting?..................................................................... 108 IntermittentCalorieRestriction ......................................................................................... 109 MyExperienceWithIntermittentCalorieRestriction ................................................... 112

Exercise............................................................................................................................... 112 PreandPostWorkoutNutrition....................................................................................... 113 Summary ............................................................................................................................ 113

Terminology............................................................................................................................ 115 References.............................................................................................................................. 119


6

Foreword

Thisbookismyattempttosummarizetheimportantfindingsinthescientificliteratureandmyownexperiencesastheyrelatetogettingridofinsulinresistance.Itisnotatextbookonexplaininginsulinresistance;suchbookscanbefoundelsewhere.Noonefullyunderstandsinsulinresistanceyet.Thereisjustsomuchthatsciencehasuncoveredaboutthesubject.Manyquestionsstillremain,sonoonecanreallyclaimtoknowtheentirefieldbecausemanythingsaresimplynotknownyet.Whatisknown,though,isthatthisisahugehealthproblemwhichcontributesto,ordirectlycauses,numerousseriousailments.Fortunately,weknowalotabouthowtoreversethiscondition.Asbadasitistobeclassifiedasinsulinresistant,thisdiagnosis,ifyouhaveit,isactuallyquitehopefulbecauseinsulinresistanceislargelyacauseofadversefactorswithinyourcontrol,suchaslifestyle.Infact,insulinresistancerespondsverywelltolifestylechanges.IknowbecauseIveseenithappeninmyownlife.Soinsteadofbeingdisheartenedatthiscondition,behappythatyoureatleastafflictedwithsomethingyoucanchange.Everyoneisnotsolucky.Personally,Ithinkitsaprivilegetoliveahealthylifeand,yes,therearesomesacrificesandworktobedone,butitsbetterthanthealternative.Sodontbelazy,behealthy.Andbethankfulthatyouatleast1)haveaconditionthatrespondstolifestylechanges(thingscouldbemuchworse)2)havefoundthisbookthatwillsetyouontherighttrack.Awordofwarning,though:Thestrategiesinthisbookarequitepowerfulandmaynecessitatereductionordiscontinuationofmedicationsthatyoumaybetaking.Alwaysworktogetherwithyourdoctorifyoudecidetomakeanylifestyleordietarychanges.Alldisclaimersapply.Iwishyougreatsuccessonyourjourney.AndIdreallylikeyourfeedbackonmybook(good,badorugly).Youknowhowtoreachme.


7

Yoursinhealth.MartinMalmberg


8

Introduction

Iwilltrytoexplainthiscomplexfieldineasytounderstandterms.Moreimportantly,Iwilltrytoexplainhowtogetridofinsulinresistance.Ifyoureunfamiliarwithanyterms,youcanalwaysrefertothechaptercalledTerminology.Onthatnote,whenIwritecaloriesImeankilocalories,alsoknownaskcal.Caloriesisusuallythewordthatpeopleuseforconveniencewhentheymeankilocalories.Ihaveusedthatstyleaswell.

What is insulin resistance? Insulinresistanceissimplyalessthannormalresponseinvarioustissuessuchasmuscleandlivertoinsulin.Insulinresistanceitselfisnotadisease,butmerelyastateabadone,Imightadd.Muchlikeobesityisnotadisease;itsastatethatcanleadtodisease.Beforewegoonyoushouldunderstandthefollowing:

Insulinsensitivityisgood Insulinresistanceisbad

Itmayseemabitcounterintuitive,soletmeexplain.Normallywhenweresensitivetosomething,itsbad.Ifweresensitivetonuts,orsunexposure,orpollenitsbad,right?However,whenweretalkingaboutinsulin,youwanttobeassensitiveaspossible.Why?Becausewhenyoureinsulinsensitive,thecellsinyourbodyaresensitivetotheeffectsofinsulinandonlyasmallamountofinsulinisrequiredtogetitsjobdone.Thisjobisamongotherthingskeepingbloodsugarincheck.Sowhatwereallymeanwhenwesaygetridofinsulinresistanceisincreaseinsulinsensitivity.Itsmoreorlessthesamething.


9

How does insulin resistance lead to disease? Whatfollowsisanextremelysimplifiedversionofevents,withmanybitsleftout,relatinginsulinresistancetoovertdisease,butitshouldhelpyouunderstandinsulinresistancebetter.Thebestknown,butfarfromonly,jobofinsulinistokeepbloodsugarfromgoingtoohigh,andthisisacriticaltaskbecausehighbloodsugarisdangerous.Intheinsulinsensitivestate,onlyacomparativelysmallamountofinsulinisrequiredtokeepbloodsugarincheckandregulatevariousotherbodilyfunctions.Ourbodiesworkbestinthisstate.Intheinsulinsensitivestate,insulinlevelsarecomparativelylowbuttheresponseofvariouscellstotheinsulinisstillnormalbecausethecellsarequitesensitivetoinsulin.Intheinsulinresistantstate,ontheotherhand,sometargettissueshaveabluntedresponsetoinsulin.Thiscanbecausedbyvariousfactors,aswillbeexploredinthisbook.Wheninsulinresistanceispresent,itbecomesdifficultforinsulintokeepbloodsugardowninthenormalrange.Theexpectedresponsewouldbeelevatedbloodsugar.Butnotsofast!Topreservenormalbloodsugar,thepancreaswillattempttoproduceandsecretemoreinsulin.Thisprocessiscalledcompensatoryhyperinsulinemia,i.e.highinsulinlevelstocompensateforthepoorresponseoftargetcellstoinsulin.Thisisonlylogicaland,ifsuccessful,thisprocesswillmaintainprettynormal(althoughusuallynotoptimal)bloodsugar.Sowhatstheproblem,then,aslongasbloodsugariskeptincheck?Well,thepriceforkeepingbloodsugarincheckthiswayishighinsulinlevels,alsoknownashyperinsulinemia.Sowhat,youmayask.Iftherearehighinsulinlevelsintheblood,butthecellsrespondpoorlytothem,wouldnttheoverallresponsebenormal?Yes,butnotalltissuesbecomeinsulinresistanttothesamedegree.Insulinsignalingmaybebluntedinsomebiologicalpathways(processes),whileitispreservedinothers[8][10].Theendresultisanimbalance,wherebyinsulinsignalsasymmetrically,andthisisnotcool.Highinsulinlevels/insulinresistancewithsometimesresultinghighbloodsugar(seebelow)havebeenimplicatedincausingorexacerbatingthefollowing.

Prediabetes(highfastingand/orpostmealbloodsugar)(seebelow) Type2diabetes(veryhighbloodsugar)[8](seebelow) heartdisease[8] Alzheimersdisease[7] acne


10

aging(?)[12][13][14] malepatternbaldness(mostcommonformofhairloss),especiallyifclearly

noticeablebeforeage35 certainformsofcancer(notablyprostate,breastandcolon[11])orpossiblyall

cancers[10] PCOS(polycysticovarysyndrome)[19][23] 4of5componentsofthemetabolicsyndrome[9][16][22]:

o depressedHDLcholesterolo highbloodsugaro highbloodpressure[21]o hightriglycerideso (the5thcriteriaexcessfatisnotaconsequenceofIRbutincreasesthe

chancethatapersonwillbeinsulinresistant[18]) andmore

Whydoesnteveryinsulinresistantpersongetalloftheabove?Probablyduetoindividualgeneticmakeupandotherenvironmentalfactors.Most,ifnotall,oftheaboveailmentscanalsobecausedbyfactorsotherthaninsulinresistance/hyperinsulinemia.Nevertheless,highinsulinlevels/insulinresistancehavebeenlinkedtoalloftheabove.

Insulin resistance can lead to high blood sugar, too (prediabetes, type 2 diabetes) Insulinresistancecommonlyleadstohighbloodsugar,butthisdoesnthappeninallindividuals.Thereareplentyofindividualswhoareinsulinresistantbutretainvirtuallynormalbloodsugarlevels,butatthecostofhighinsulinlevels,asexplainedabove.Nevertheless,ifinsulinresistanceworsensand/orthepancreascantsecreteenoughinsulintocompensatefortheinsulinresistantstate,bloodsugarwillstarttorise,Thiscanleadtoastateofprediabetes,whichmeansabovenormalbloodsugar,butnotenoughtobeclassifiedasatype2diabetic,althoughprediabetesoftenprogressestoT2D.Whattypicallyhappensfirstisthatyourbodyhastroublekeepingdownbloodsugarimmediatelyafteryoueatcarbohydrate.Ifthingsdeterioratefurther,yourbodywillhavetroublekeepingdownbloodsugarevenwhenyouhaventeatenanythingfor812hours.Inotherwords,postmealbloodsugarcontrolusuallybreaksdownbeforefastingbloodsugarcontrol[6,page20].Butevenbeforethishashappened,thepersonhasusuallybeeninsulinresistantforaperiodoftime,whilsthavinghadnormalbloodsugarbuthighinsulin.Highbloodsugaristheabnormalitymostcloselyrelatedtoinsulinresistance[18].Evenwitharelativelymilddegreeofinsulinresistance,bloodsugarcanbegintorise.


11

Ifinsulinresistanceprogressesfurther,type2diabetesdevelops.Type2diabetesisdiagnosedwhenveryhighbloodsugarispresent,sotype2diabetes=veryhighbloodsugar.Type1diabeticscanalsogethighbloodsugar,becausetheirpancreashascompletelystoppedproducinginsulin,butthatisanotherthing.Ontheotherhand,mosttype2diabeticssecreteplentyofinsulin,butaresoinsulinresistantthatithaslittleeffect.Theendresultishighbloodsugar.Incidentally,sincetype2diabetesischaracterizedandusuallycausedbyinsulinresistance,Illbereferringtomanyscientificstudiesperformedontype2diabetics,becausetheyserveasagoodgroupforstudyinginsulinresistance.

What are the dangers of high blood sugar? Chronicallyelevatedbloodsugarcausesdiabeticcomplications.Doesntsoundtoobad,doesit?However,whatitmeansis:

Nervedamage(neuropathy).Itisusuallyfeltfirstinthefeetasatinglingorburningsensation,typicallyinbothfeet.Itcanalsoaffectfingersandarms.Eventuallytheaffectedareascangonumb,andthewholeprocesscaneventuallyleadtoamputationoftoes,feetandfingersduetogangrene.[6,page41]

Impotence.Itmightbecausedbynervedamage.[6,page41] Gastroparesis,i.e.thefailureoffoodtoleaveyourstomachaftereating,alsocanbe

causedbynervedamage.[6,page41] Kidneydamage/failure(nephropathy).Highbloodsugaristhoughttoplayamajor

roleinthis,andcanleadtototalkidneyfailurewhichwillrequireregulardialysisorakidneytransplant.

Pancreaticbetacelldysfunctionanddeath.Thisisreallyatragicandunfairconsequenceofhighbloodsugar.Pancreaticbetacellsaretheverycellsthatproduceinsulintokeepbloodsugardown.However,theyarevulnerabletohighbloodsugaranditwilldamageorkillthem.Atthatpoint,theycannolongerproduceanyinsulin,leadingtoevenhigherbloodsugar,andthetype2diabeticwillhavetoinjectinsulinfromanoutsidesource.[6,page4345]

Permanentblindness(duetoretinopathy).Theretinaisvulnerabletohighbloodsugarandcanbedestroyedbyit.[6,page45]

Thesecomplicationscanbegintooccurevenintheprediabeticrange,beforebloodsugarrisesintothetype2diabeticrange[6].Sojustbecauseapersondoesnthavetype2diabetesdoesnotmeantheyresafe.Moreover,manypeoplehaveprediabetesortype2diabeteswithoutknowingit.Ifyouhaventtestedyourbloodsugarlevelslately,howdoyouknowyoudont?Whenapparentsymptomsarise,irreversibledamagemayalreadyhaveoccurred.Torecap:


12

Chronicallyhighinsulinlevels(duetoinsulinresistance)arebad,whetherinthefastedstate(afternofoodfor812hours)oraftereating.

Chronicallyhighbloodsugarlevelsarebad,whetherinthefastedstate(afternofoodfor812hours)oraftereating.

Transientinsulinandbloodsugarspikesimmediatelyaftereating,whicharequicklyreduced,arenormalandnotdangerous.

Insulin sensitive or insulin resistant? Thats the question Eveninthenormal,apparentlyhealthypopulation,insulinsensitivityvariesasmuchas600800%[16]ormorebetweenthemostinsulinsensitiveandthemostinsulinresistantindividuals,andthethirdthatismostinsulinresistantreportedlyhaveanelevatedriskofdevelopingovertcomplicationsofinsulinresistance[17].Thatisahugepartofourpopulationwhenyouthinkaboutit.Mosteveryonehassomedegreeofinsulinsensitivity.Ifapersonhaslowinsulinsensitivitythepersoncanbesaidtobeinsulinresistant.Ifapersonhashighinsulinsensitivity,thepersoncanbesaidtobeinsulinsensitive.Thinkofitlikethis:

Asyoucansee,wecouldsaythatinsulinresistance=lowinsulinsensitivity.Becomingmoreinsulinsensitiveisthefocusofthisbook,andgettingoutofthatstatethatwemightcallinsulinresistant.ButasfarasIknow,therearenotruedefinitions,noobjectivecutoffpointsbetweenthesestates,justacontinuumthatyoucanmoveyourselfalong[15].Wecouldcall,forinstance,theleastinsulinsensitivethirdofthepopulationinsulinresistant.Butthatwouldmerelybeanoperationaldefinition,notnecessarilyabiologicaltruth.WhatImtryingtosayisthathigherinsulinsensitivityisalwaysbetter[22]anditminimizestheriskoftheentireclusterofproblemsdescribedabovecausedbyhighinsulinandhighbloodsugarlevels.Whenyouvegottenoutoftheinsulinresistantstate,great.Butwhynotgoontobecomeevenmoreinsulinsensitive?


13

Highinsulinsensitivitywillkeepbloodsugarandinsulinlevelsdowninthenormalrange,butnotdangerouslyorinappropriatelyso.

How to diagnose insulin resistance and track progress Itmaybehelpful,althoughnotrequired,toknow:

Yourcurrentdegreeofinsulinsensitivity Yourprogressorlackofprogresstowardsincreasedinsulinsensitivity

Thetestsdescribedbelowwouldtypicallybeadministeredbyyourdoctor,ifnothingelseisstated.Thegoldstandardformeasuringinsulinsensitivity,isamethodknownastheeuglycemichyperinsulinemicclamp.Briefly,itworksbyinfusinginsulinintoaveinuntiladesiredandknownlevelofinsulinisreachedintheblood.Atthesametime,glucose(bloodsugar)isinfusedinaveinuntilasteadybloodsugarlevelisreached.Thebetterapersonsinsulinsensitivity,thehighertherateofglucoseinfusionwillbesincetheinsulinleveliskeptconstant.Inotherwords,ahighglucoseinfusionrateshowsthattheinsulineffectivelyhelpsclearbloodsugarfromtheblood.Alowglucoseinfusionratemeansthattheinsulinhasalessthannormaleffect(i.e.insulinresistance)[1].Theeuglycemichyperinsulinemicclamptest,though,ismostlyusedforresearchpurposes,butitistheonlytruewaytomeasureinsulinsensitivity.Therearealternatives,though.ArelativelysimpletestthatyourdoctorshouldbeabletohelpyouwithistheHOMAIR(homeostaticmodelassessmentofinsulinresistance)[2].Tocalculatethisyouneedtomeasurefastinglevels(i.e.afternofoodordrinkfor1012hours)ofinsulinandplasmaglucose,whicharethenenteredintoanequationlikethis:HOMAIR=InsulinxGlucose/22.5InsulinshouldbeinsertedinmU/Landplasmaglucoseinmmol/L.Ifyourglucosevalueisgiveninmg/dl,usethefollowingformula:HOMAIR=InsulinxGlucose/405HOMAIRmeasuresyourinsulinsensitivitybycheckinghowmuchcirculatinginsulinisrequiredtokeepyourbloodsugaratacertainlevel.Lowerinsulinorlowerglucose,orboth,wouldthusgivealowerinsulinresistance.Thiscorrelateswellwiththehyperinsulinemic


14

euglycemicclampmethod.Avalueof1isgood[2]butisprettystringent.IfyourHOMAIRdeclines,itsasuresignthatinsulinsensitivityhasincreased.AsurrogatewayofmeasuringinsulinresistanceistheOGTT(oralglucosetolerancetest).Itistypicallyperformedbydrinkinginthefastedstate75grams(roughly20teaspoons)ofglucosedissolvedin250mlofwater.Sinceglucoseisthesameasbloodsugaritdoesntneedtobemetabolizedandentersthebloodstreamrapidly,obviouslyleadingtoincreasedbloodsugarlevels.Yourbodysabilitytobringdownthebloodsugarintothenormalrangegivesanindicationofyourinsulinsensitivity.Typically,bloodsugarismeasured2hoursafterdrinkingthesolution,aftersittingquietlyfor2hours.However,itmustbementionedthattheOGTTdoesntexclusivelymeasureinsulinsensitivity.Yourbodysabilitytobringdownbloodsugarisdependentlargelyon

Insulinsecretionfromthepancreas Insulinsensitivity(i.e.theresponseofcellstothatinsulin)

Ifanyoftheseareimpaired,yourbloodsugarcontrolwillbeimpaired.Soahigh2hourOGTTvalueindicateseitherimpairedinsulinsensitivityorimpairedinsulinsecretion,orboth.Therefore,itsnotaperfectmeasureofinsulinsensitivityperse.Nevertheless,ahigh2hourOGTTvalueisusuallyastrongsignofinsulinresistance[16].A2hourOGTTbloodsugarvalueinthenormalrangedoesntnecessarilyexcludeinsulinresistance,however.Itcouldjustmeanthatyourpancreasissecretinglotsofinsulintocompensateforyourinsulinresistance,whichwouldleadtonormalbloodsugar.Twentyfivepercentofthosewithnormal2hourOGTTvaluesarestillinsulinresistant[22].Anormal2hourOGTTbloodsugarvalueshouldbe


15

perfectlynormalfastingbloodsugarvalueisinthe7085mg/dlrange(3.94.7mmol/l)[6,page11].Fastingbloodsugarvaluesinthe100125mg/dlrange(5.557.0mmol/l)areconsideredprediabetic[5]andasignofinsulinresistance.Butmostinsulinresistantindividualshaveafastingglucoseconcentrationlowerthan110mg/dl(6.1mmol/l)[20].Anyconsistentreadingsabove90mg/dl(5mmol/l)areacauseofconcernandshouldbeinvestigatedcloser.However,alowfastingbloodsugardoesntmeanmuch,becausethepersonmaystillhaveelevatedinsulinlevels,indicatinginsulinresistance.Moreover,ahighfastingbloodsugardoesntnecessarilymeaninsulinresistance,either,because,aswiththeOGTT,ahighreadingcouldalsosimplymeanthatinsulinsecretionisimpaired.Therefore,thistestisquitecrude,butwhencombinedwithafastinginsulintest,itcanbecombinedtocalculatetheHOMAIR(describedabove)whichismuchmorereliable.Ifyouwanttobecertainthatyoureprogressingtowardsbetterinsulinsensitivity,youllhavetouseoneofthesemeasuresregularly.Forinstance,ifyouweretotakeanOGTTtomorrowandyour2hourbloodsugarvaluewas150mg/dl(8.3mmol/l),thenthatwouldindicateprediabetesorinsulinresistance.Ifyouimplementedtheideasinthisbookand,say,3monthsfromnowtookanotherOGTTandthattimeyour2hourreadingwas110mg/dl(6.1mmol/l)(normalrange),yourbloodsugarcontrolwouldbebetter.Andthiswouldmorethanlikelybethankstoimprovedinsulinsensitivity,sincethestrategiesinthisbookareforemostaimedatincreasinginsulinsensitivity,notinsulinsecretion(althoughsomestrategiesinthisbookmayalsoimproveinsulinsecretioncapacity,whichisgoodtoo).Likewise,ifyourfastingbloodsugarwouldfallfromhightonormal,thatwouldalsoindicateincreasedinsulinsensitivity.Youmightalsonoticeimprovementsinabnormalities(suchashighbloodpressure)thatcanbecausedbyinsulinresistance.Or,ifyoureondiabetesmedications,youmightneedtodiscontinueorreducedosages.Triglycerides,ifelevated,mayfall.HDLcholesterol,iflow,mayincrease.Look,Iknowitshardtodetermineinsulinsensitivityexactly,butdontshootthemessenger,ok?Ididntmakeuptherulesabouthowthebodyworks.Whetheryoumeasureprogressornot,themethodsIdescribeinthisbookarescientificallyvalidatedandshouldimproveyourinsulinsensitivitywhetheryoutrackitornot.Morethanlikelyyouwillnoticeyourhealthimprovedramaticallyinanumberofwaysifyouimplementthestrategiesinthisbook.


16

How to get the most out of this book Somethingscauseinsulinresistancetransiently,suchascaffeine.Onceitleavestheblood,afterafewhours,theinsulinresistancegoesaway.Untilnexttimeyouconsumeit,obviously.Othercausesofinsulinresistancearemorechronic.Likehighironlevels.Ifyouhavetoomuchironinyourbody,insulinsensitivitycanbeimpaired.Ironasacauseofinsulinresistanceismorechronicinnatureandcausesinsulinresistance24/7(itcanbefixed,though).Itsimportanttoremovethechroniccausesofinsulinresistance,ortheywillbeeverpresentandalwaysimpairyourinsulinsensitivity.Ifyoudontgetridofthem,youmaystillbeinsulinresistantnomatterwhatyoudo.Itsimportanttoavoidinducingshortterminsulinresistanceonaregularbasis,too,ofcourse.Onthatnote,Ihavestrungtogetherthechaptersinthisbookinageneralorderofimportance,basedonmypersonalexperiencewithinsulinresistance.Ofcourse,individualneedswillvary,butformostpeopleIguessthattheywillneedtoprioritizeaccordingtothefollowinglist:

1. Losebodyfat(ifapplicable)2. Getridofexcessiron(ifapplicable)3. Exercise4. Taketherightsupplements5. Sleepwell6. Manipulateyourdiet7. Additionally,appendixAcontainsacompleteguidetoweightlossspecificallyfor

insulinresistantpeople,ifyoudontknowwhattodo.Inmyexperience,dietistrulytheleastimportantthingforimprovinginsulinsensitivity.Dietisstillimportant!Justnotasimportantasmanyotherauthorsthink.Dietsupportstheotherinterventions,andagooddietbyitselfcanimproveinsulinsensitivity.Yourdietwillhelporhinderalltheotherareas,butitdoesntmakesensetotrytoimproveyourinsulinsensitivitywiththeperfectdietwhenyoure45kg(100pounds)overweight,orhaveexcessiveironstores,orneverexercise.Itwouldbebettertofixthosethingsfirst.Noamountofdietarymaneuverswillgetridofyourinsulinresistanceinthefaceof15abovebeingscrewedup.Iwouldactuallyworkon16allatthesametime,butifIhadtoprioritizeIddoitintheorderabove.Withthatsaid,letsexaminehowtoimproveinsulinsensitivity.


17

Chapter 1 Body Fat and Insulin

Resistance

Fact:Notalloverweightorobesepeopleareinsulinresistant.Fact:Notallinsulinresistantpeopleareoverweight/obese.Ifaninsulinsensitive(notinsulinresistant)overweightindividuallosesfat,notmuchofanimprovementwillbeseeninhisorherinsulinsensitivity.[26]Butifaninsulinresistantoverweightindividuallosesfat,bigimprovementswilltypicallybeseen.[26]Moreover,alotofpeoplesufferfromhiddenobesity,whichisfarfromapparent.Theylooklean,buttheyareactuallyobese,asweshallsee.Formostofmyreaders,thiswillbethemostimportantchapterofthebook.Sopayattention,evenifyouthinkyouknowwhatImabouttosay.Eightyfivepercentoftype2diabeticsareoverweighti.e.haveaBMIof25ormore.[1]Overweight(BMI2530)andobesity(BMIgreaterthan30)areassociatedwithahigherriskofinsulinresistance,prediabetes,elevatedfastingbloodsugarandtype2diabetes[3]andhigherBMIstranslatetogreaterriskoftheaforementionedconditions.Insulinresistanceinturnincreasestheriskofheartdiseaseandstroke[15]etc.andIRisonelinkbetweenexcessweightandheartdiseaseandstroke.YoucancalculateyourownBMIhere:http://www.nhlbisupport.com/bmi/InsulinresistanceisnotrestrictedtopeoplewithBMIgreaterthan25;riskofIRandrelatedcomplicationsincreaseseveninthe2025rangeandbeyond[5].Notonlyisinsulinresistancemorecommonamongoverweightindividuals,overfeedingdirectlypromotesIR.


18

Ina2010study,36healthyindividualswereoverfedby1250caloriesperdayfor28days.Fastinginsulinandbloodsugarbothincreased,causingadecreaseofinsulinsensitivityby11%.Interestingly,fatmassincreasedonlyby1.1%,indicatingthatevenasmallfatgaincancauseadeteriorationofinsulinsensitivity.Theweaknessofthisstudywasthelackofaweightstabilizationperiodaftertheweightgain;suchaperiodmayhavediminishedthelossofinsulinsensitivitysomewhat.Nevertheless,thisstudyclearlyshowsthatoverfeedingleadstofatgainandlossofinsulinsensitivity.[21]

Beyond Body Mass Index BMIisnotthebestwaytomeasurethepresenceofexcessfatonaperson.ApersoncanhaveahighBMIthankstoplentyofmusclemass,yethavelittlebodyfat.Conversely,itispossibleforapersontobeintheBMI2025range,conceivablyevenlower,andstillcarryexcessfatthatcausesinsulinresistance.Sincethe1980sithasbeenincreasinglyrecognizedthatfatdistributionisamoreimportantdeterminantofinsulinresistancethantotalamountofbodyfat.Fatcanbestoredindifferentlocationsinthebody,forexample:

intheliver(intrahepaticfat) insidethemuscles subcutaneously(undertheskin,outsidethemuscles;thisisthefatrightunderneath

yourskinthatyoucanpinchwithyourfingers) intraabdominally(insidethecavityformedbytheabdominalmusclesinthefront

andthebackmusclesintheback,i.e.aroundtheinternalorgans.Youcannotseeorfeelthisfatdirectly.)

otherplacesEveryonehasabitoffatineachoftheseplaces,ofcourse.Dependingonwherethefatisstored,itwillhavedifferenteffects.Itisestablishedthatacentralfatdistributionismoredangerousthanaperipheralfatdistribution[2].Centralfatdistributionreferstofatbeingstoredpreferentiallyasintraabdominalfatandsubcutaneousfatonthebelly.Aperipheralfatdistributionreferstofatbeingstoredpreferentiallyassubcutaneousfatonthebuttocks,hips,legs,andotherplaces,whilelessisstoredintraabdominallyorassubcutaneousabdominalfat.Moreover,intraabdominalfatseemsmorecloselyassociatedwithinsulinresistancethandoessubcutaneousabdominal(belly)fat[6][7][8][9],althoughthisisnotundisputable.Nevertheless,acentralfatdistributionremainsabiggerriskfactorforinsulinresistancethantotalbodyfat,whetherthatfatisstoredintraabdominallyorsubcutaneouslyonthebelly.Visceralfatisasubtypeofintraabdominalfatandagedratswhosurgicallyhavetheirvisceralfatremoved,increasetheirinsulinsensitivitymarkedly.Thisistosomeextentalsoseeninagedratswhohavethesameamountofsubcutaneousfatremovedsurgically,butthepositiveeffectoninsulinsensitivityismuchgreaterwhenvisceralfatisremoved[25].Thisindicatesthatdeteriorationofinsulinsensitivityseeninagingmaynotbeduetoage


19

itself,butduetoaccumulationofvisceralfatfirstandforemost,whichluckilycanbecounteractedasweshallsee.Somedifferentmeasurementshavebeenproposedtodeterminewhetherapersonhastoomuchcentralfatornot.ThemostaccuratewaystodetermineamountsofintraabdominalfatisbyCTscan(computedtomography),MRI(MagneticResonanceImaging)orultrasound.Thesearehightechmeasurements,andaretheonlyonescapableofdistinguishingbetweeninternalandexternalfat,butbeforetheywereinventedresearchersreliedonothermeasures.Twosuchmeasuresarewaisthipratio(WHR)andwaistcircumference.However,noneofthemcancomparetotheaccuracyofCTscan,MRIorultrasound.

Waist-to-Hip-Ratio Thewaisttohipratioiscalculatedbyfirstmeasuringyourwaistcircumferenceanddividingthatnumberbyyourhipcircumference.E.g.ifyourwaistcircumferencewas30in(76.2cm)andyourhipcircumferencewas32in(81.3cm),yourWHRwouldbe:30/32=0.94Itdoesntmatterifyourmeasurementsareincentimetersorinches,becausethisisaratio.AhighWHRmeansthatthepersonhasalotoffatstoredcentrally(aroundthebelly)comparedtothehips,whichisconsidereddangerous.Proposedthresholdvalues,i.e.abovewhichanincreasedriskofIRisbelievedtoexist,are0.85forwomenand0.95formen[2],butothervalueshavealsobeenproposed.AlowerWHRratioisneverthelessbetter.InastudyamongwomenfromSweden,WHRaswellasbodyweight,BMI,waistcircumferenceandmorewasmeasured.Twelveyearslaterthewomenwerefollowedupon,anditwasconcludedthatahigherWHRatbaselinewasastrongpredictorofsufferingheartattack,chestpain,strokeordeathduringthefollowing12years[4].Inthesamestudy,itwasfoundthatWHRincreasedwithage.Also,amongthe10%ofwomen(140individuals)withthelowestWHRnotasinglesufferedaheartattackorstrokeduringthose12years!Inasimilarstudyitwasfoundthat,among54yearoldmenfromSweden,WHRratioprovedtobeabetterpredictorthanBMIorskinfoldmeasurementsforriskofheartdisease,strokeordeaththefollowing13years.Quotedfromthestudyamongthe10%withthelowestwaisttohipcircumferenceratiosnotasinglemandevelopedstroke.[22]YoucanreadmoreabouthowtoaccuratelymeasureWHRhere:http://en.wikipedia.org/wiki/Waisthip_ratioEventhoughWHRisbetterthanBMIforestimatingthepresenceofdangerouscentralbodyfat,itisstillfarfromperfect.Forinstance,inthestudyreferencedinthebeginningofthischapter[21],WHRdidnotincreaseinresponsetooverfeeding,eventhoughBMI,waistcircumferenceandpercentbodyfatallincreased,showingthatWHRdidntpickupthefatgainthatledto11%decreasedinsulinsensitivity.


20

Another,better[2],waytoestimateyourlevelsofdangerouscentralfatissimplybymeasuringyourwaistcircumference.

Waist circumference Thehigherthewaistcircumference,themorecentralfatapersontendstohave,andtheworsetheinsulinsensitivity.Thus,aswithWHR,alowerwaistcircumferenceisbetter.Youcanreadmoreabouthowtomeasurewaistcircumferencehere:http://en.wikipedia.org/wiki/Waisthip_ratioOutofthesetwoestimatesofintraabdominalfat,waistcircumferenceissuperiortoWHR[2].However,neitherWHRnorwaistcircumferencecandistinguishbetweenintraabdominalfatandsubcutaneousabdominalfat,i.e.ifthepersonsfatisinternalorsubcutaneous;theyjustshowthatapersonhasalotofcentralfat.AmongKoreanmenandwomen,onlywaistcircumference(notBMI)inmenwasariskfactorfortype2diabetes,whileforwomenbothwaistcircumferenceandBMIwereriskfactorsbutWCwasmoreaccurate[24],showingthesuperiorityofwaistcircumferenceoverBMI.AswithWHR,therehavebeenattemptstodevelopcutoffpointsforadangerouslyhighwaistcircumference.However,thiseffortiscomplicated,reportedly[2],byvaryingeffectsofwaistcircumferenceonIRindifferentpopulationsandgenders.Inotherwords,whatmaybeadangerouslyhighwaistcircumferenceforoneperson,maynotbeaproblemforanotherperson,andthismayvarybygenderorethnicity.Somecutoffpointsforwaistcircumferencehaveneverthelessbeenproposed,forexamplemorethan100centimeters(39.4inches)[2]inmenandwomen.However,increasedriskofobesityassociatedcomplicationshavebeenfoundalreadyatwaistcircumferencesof94cm(37inches)and80cm(31inches)inmenandwomen,respectively[2].Anotherpointworthmentioningaboutwaistcircumferenceandinsulinresistanceisthatsomepeoplehavealargewaistcircumference,yetretaingoodinsulinsensitivity.Thisisprobablybecausewaistcircumferencecannottakeintoaccountwhetherfatisstoredsubcutaneouslyorintraabdominally.Thiswasillustratedina2010studycarriedoutinGermany[8].Theresearchersexamined30morbidlyobesemenandwomenwithaBMIaround45(extremelyfat).Theyhad50percentbodyfatandtheiraveragewaistcircumferencewas132cm(52inches),sotheyshouldhavebeenprofoundlyinsulinresistant,right?Interestingly,theyhadgoodinsulinsensitivity,althoughnotsuperb.Whencomparedto30equallymorbidlyobesemenandwomenofthesameage,percentbodyfatandgender,butsufferingfromIR,itwasfoundthattheIRgroupofmorbidlyobesepeoplehadonlya6cm(2.4inches)greaterwaistcircumference,whichwasstatisticallysignificant.However,thisisquiteasmalldifferenceanyhow.


21

Torecap,theinsulinsensitiveobesepeoplehadanaveragewaistcircumferenceof132cmwhiletheaveragewaistcircumferenceoftheinsulinresistantobesepeoplewas138cm.Bothgroupsweremixed,consistingoftwothirdsmen.Aswecansee,everyoneswaistcircumferencewasfar,farabovethecutoffpointsmentionedearlier,yetsomeofthesemorbidlyobesepeopledidnothaveIR.Whatgives?UponexaminationbyCTscan,itwasrevealedthatthemaindifferencebetweentheinsulinsensitiveandinsulinresistantpeoplewastheamountofvisceralfat.Whiletheinsulinresistantobesehadonlya6%greaterwaistcircumference,theyhad129%morevisceralfatasrevealedbyCTorMRIscan.Thus,wewitnessagainhowintraabdominalfatseemstohaveamoreprominentroleincausingIRthandoessubcutaneousfat.Avisualexampleofindividualsfromthe2differentgroupscanbeseenhereandisquiterevealing:http://ajpendo.physiology.org/content/299/3/E506/F3.large.jpgHowreliablearewaistcircumferencecutoffpointsreallywhensomepeoplearefaraboveandstillretainnormalinsulinsensitivity?Theoppositecanbetrueaswell.Apersoncanbequiteleanbyallregularmeasures,suchasBMI,WHRandwaistcircumference,yetstillbeeffectivelyobese.Thatswheretheconceptofmetabolicobesitycomesin.

Redefining obesity Understanding metabolic obesity Listenup,becausethisisacriticallyimportantconcepttograsp.Asreportedmorethan30yearsagoandsummarizedneatlybyRudermanandcolleaguesin1998[5],theoccurrenceisquitecommoninthegeneralpopulationofthesocalledmetabolicallyobese,normalweightindividual,whoisinsulinresistantandalsodisplayotherfeaturesoftheinsulinresistancesyndrome,yethasaBMIaslowas20andconceivablyevenlower.Inessence,metabolicallyobesepeopleareeffectivelyinsulinresistantyethavealowornormalBMI.Whatcausesmetabolicobesity?Theansweryoumayhaveguesseditbynowseemstobealargeproportionofcentralabdominalfat.Inotherwords,intraabdominalfatandsubcutaneousfatonthebelly.[5]Howdoyouknowifyousufferfrommetabolicobesity?Itcanbequitedifficulttorecognize,butaquestionnaireformenandwomenaged2055yearswithaBMIof2027hasbeensuggestedandcanbeviewedonpage6ofthefollowingPDF:http://diabetes.diabetesjournals.org/content/47/5/699.full.pdf(LetmeknowifthelinkstopsworkingandIwillfixit.)Isuggestyoufamiliarizeyourselfwiththisquestionnaireandtakeittoyourdoctorifnecessary.So,firstofall,metabolicobesityofnormalweightindividualsonlyappliestopeoplewhoareNOTtraditionallyconsideredobeseoroverweight.IthasbeenfoundthatevenintheBMI


22

rangeof2027theriskofmetabolicobesityincreaseswithhigherBMI.TheloweryourBMI,theloweryourriskofmetabolicobesity.[5]Personally,metabolicor,asIliketocallit,hiddenobesitywasmymainsourceofinsulinresistance,andacauseofmuchpersonalfrustration.IalwaysusedtobequiteleanwithaBMIcloserto20than25,yetdisplayedinsulinresistanceeveninadolescence.WhereverIwouldpinchmyselfonthebodyIwouldgetquiteasmallskinfoldmeasure,i.e.therewasnotmuchsubcutaneousfat.However,Ialwayslookedpregnant(IremindyouthatImmale),andIcouldneverunderstandwhy.Evenonphotosfrommyearlyyears(4yearsoldetc.)Iwouldhaveanexcessivelylargebellythatprotrudedunnaturallyfrommybody.IlookedlikeIhadswallowedabasketball.ButIneverunderstoodwhatcausedthisIputitdowntolargeorgans,orbigmeals,becauseIhadneverheardofanddidnotunderstandtheconceptofmetabolicobesity.Thefactthatnooneelsenotdoctors,notparentstooknoticemademethinkitwasnormal.Specifically,Ididnotunderstandthat1)apersoncanstorefatintraabdominally2)apersoncanotherwisebeveryleanyethaveaverylargeproportionandmassoffatstoredintraabdominally.Thiswaswhatcausedmybellytoprotrude.LaterwhenIstartedstrengthtrainingatage23IgottothepointwhereIevenhadvisiblesixpackabs,indicatingalowsubcutaneousbodyfatpercentage.However,mybellystillprotruded,becauseIhadapropensitytostorefatintraabdominally.Ithinkalotofpeopleareinthissituation,thatswhyImstressingthispoint.Ifyourevisiblyoverweightorobese,atleastitsapparent.Butinthecaseofleanindividuals,itmustbeclarifiedthattheytoocaneffectivelybeobese,duetoexcessabdominalfat,andthisisrarelyapparent.Furthermore,metabolicobesityofnormalweightindividualsseemstobequiteadangerousstate.Forinstance,onestudyamong54yearoldmenfoundthatthegreatestriskofdeathwasfoundinmenwhohadthelowestBMIcombinedwiththehighestWHR;inotherwords,thesemenwereoverallquiteleanbuthadahighproportionofcentralfat[22],andwouldprobablybeclassifiedasmetabolicallyobese,normalweightindividuals.Forsuchametabolicallyobeseperson,waistcircumferencecutoffpointsof71.1cm(28in)and86.4cm(34in)forwomenandmen,respectively,havebeenproposed[5].Thiswouldindicatethatanywaistcircumferencebelowthosevaluesisfine,butIdisagree.Idothinkthequestionnairereferredtoaboveisagoodstartingpoint,though.Oneadditionalcommentmustbeinterjectedhere.NoteveryleanindividualwhohasIRhasexcessintraabdominalfat.ThereAREothercausesofIRnotrelatedtobodyfat.Butifyouareleanandinsulinresistant,beveryobservantofanyexcessintraabdominalfatyoumayhave.Ifwegobacktowaistcircumferenceforamoment,wecanseethatthereareinsulinsensitivemorbidlyobesepeoplewith50%bodyfat,BMI45andwaistcircumferencearound132cmormore,aswellasinsulinresistant,normalweightpeoplewithaBMIinthelow20sandawaistcircumferencefarbelow100andevenfarbelow90.


23

Thisshowsthatwaistcircumferenceisnotaperfectmeasuretogoby,either.

What causes a central fat distribution? Everyonehasabitofcentralfat,itisonlynatural.Thequestionis,whydosomeindividualsstorealargeproportionoftheirfatcentrallymorespecifically,asintraabdominalfatandcanthisbechanged?Itisnotfullyknownwhythishappens,butthereasonitatleastpartiallygenetic,perhaps3055%isexplainedbygenetics[2].Also,vanLentheandcolleaguesfailedtofindmuchsupportfortheroleofenvironmentalfactorsinthedevelopmentofcentralfatingirlsandboysfollowedfrom13to27yearsofage,andconcludedthatacentraldistributionofbodyfatwasmainlydeterminedbygeneticandhormonalfactors[23],i.e.notsomethingthatiseasytoinfluence.Anothercommonfindingisthatmenhaveamorecentralbodyfatdistributionthanwomen[19][20],whichlikelycontributestothefactthatmenhaveworseinsulinsensitivitythanwomenwiththesameBMI[19][20],eventhoughwomenhavemoretotalbodyfat.Overconsumptionofcaloriesalongwithahighproportionofcaloriesfromfructose(fruitsugar)cancausepreferentialstorageofintraabdominalfat,accordingtoarecentstudyonhumans(reportedin[16]).However,goingsofarastoavoidfruitsbasedonthisispremature,inmyopinion.Rather,basedontheresearchersresults,itseemsamuchwiserchoicetoavoid1)sugarsweetenedbeverages2)tablesugar(alsoknownsimplyaswhitesugar;itcontains50%fructose)andhighfructosecornsyrup.Anothercauseofpreferentialstorageoffatintraabdominally,maybeinactivityandalowleveloffitness[5].Ifyouperformaerobicexercisewhilelosingweightitmayenhancelossesofintraabdominalfat,asreportedbyRudermanandcolleagues[5].Whileshortsleepmayleadtoweightgain,itdoesnotseemtopreferentiallyleadtointraabdominalfatgain[17].Chronicstressmayhavesomethingtodowithintraabdominalfatstorage[18]andarecentstudyinmenfoundthatthestresshormonecortisolcorrelatedwithincreasedamountsofvisceralfat(asubtypeofintraabdominalfat)[11]but,asfarasIknow,theconnectionisnotconclusivelyprovenanditisnotcertainwhatcouldbedoneaboutit.Smokingalsoseemstocauseacentralpatternofbodyfat,asdiscussedin[23].

Determining if you have excess fat Iwillstatethissimplywithoutovercomplicating:


24

Ifyouareapparentlyfat,byallmeansyoushouldlosefat.Thisisselfevident,andithasbeenshownthatfatlossleadstoimprovedinsulinsensitivity.

Ifyouarenotapparentlyfat,i.e.yourBMIis2025orevenless,youneedtodeterminewhetherornotyoustillsufferfrommetabolicobesity,whichischaracterizedbyexcessabdominalfatandinsulinresistanceevenwhenthetotalamountofbodyfatislow.Itcanbedifficulttorecognizemetabolicobesity,butaquestionnaireformenandwomenaged2055yearswithaBMIof2027hasbeensuggestedandcanbeviewedonpage6ofthefollowingPDF:http://diabetes.diabetesjournals.org/content/47/5/699.full.pdf(LetmeknowifthelinkstopsworkingandIwillfixit.)Isuggestyoufamiliarizeyourselfwiththisquestionnaireandtakeittoyourdoctorifnecessary.Metabolicallyobese,normalweightindividualsaretypicallyyounger,butifyouareolderthan55andunsurewhetherornotyouhaveexcessfat,youcanstilltrythequestionnaire.SinceWHRandwaistcircumferencecutoffpointsarentreliable,andBMIdefinitelyisntreliable,Isuggestyoudontpaytoomuchattentiontothese,otherthanformeasuringyourprogress.Ifyourwaistcircumferencedrops,youreontherighttrack,evenifyourbodyweightdoesnotdecline.Thiscanbethecase,forinstance,ifyoustartatrainingprogramtobuildmusclemassandlosefatyoumaygainmuscleweightwhilelosingabdominalfat.CTscan,MRIandultrasoundmayofcoursebeusedtodeterminethedegreeofintraabdominalfatyouhave,buttheyarenotalwaysreadilyavailable.Thepointatwhichvisceralfatarea(ameasurementofdangerousintraabdominalfat)asindicatedbyCTorMRIbecomesdangerousisnothigherthan133cm2(butcouldbeless),justtogiveyouanidea.Soifyouhavemorethan133cm2ofvisceralfatmeasuredbyCTscanorMRI,youredefinitelyinthedangerzone,buttheproblemsmaymanifestatevenlowerlevels.Anothermethod,perhapsthebest,fordeterminingifyouhaveexcessfatissimplybylookingandfeelingatyourself.Ifyourbellyprotrudesfromyourbodywhenyouarestandingup,relaxedandexhaled,givingyouapregnantlookorswallowedabasketballlook,thisisusuallyasignofcentralobesity.Inmyopinion,aftervoiding,whenstandinguprelaxedandexhaledyourbellyshouldnotprotrudeoutsidethefrontmostpartoftheribcage.Also,ifyouhavelargeskinfoldsonyourbellythatyoucanpinchwithyourfingers,thisisalsoasignofcentralobesity.IfyouhaveIR,youshouldactuallyexpecttofindthatyouhavetoomuchfat,becausethisisusuallythecase,althoughnotalways.Soyoucanalmostassumethatyouhaveexcessfat,unlessyouhavespecificreasontodoubtit.

What to do if you have excess fat (LOSE IT) Ifyouvecometotheconclusionthatyouhaveexcessfat,payingspecialattentiontothepresenceofanyhiddenormetabolicobesityifyouarenormalweight,itistimetodo


25

somethingaboutit.Canyouguesswhatyoushoulddoaboutit?Thatsright,youshouldlosethefat.Infact,itshouldformostpeoplebetheir#1priorityforimprovinginsulinsensitivity.Ifyoureunsurewhetherornotyouhaveexcessfat,youcangoonafatlossprogramtoseeifyourinsulinsensitivityimproves.Ifitdoes,youreontherighttrack.Everythingpointstofatlossbeingbeneficialforinsulinresistantindividuals.Forinstance,when15womenaged5873yearswithBMIsinthe29.643.8rangeunderwentjusta5%fatloss(4.7kgor10.4pounds),byeating500calorieslessthantheirexpenditureandwithoutexercise,theirinsulinresistancefellbyalmost17%.Thiswasaccompaniedbyareductionofwaistcircumferenceaswell[10].Inanotherstudy,8obesemenwithanaverageBMIof38andage2854yearswereassignedtoa3monthfatlossprogramconsistingofdietonly(noaddedexercise).Theyweregivenaliquiddietwhichsuppliedonly1000caloriesperday,whichisverylittleforobesemen.Theylostsignificantamountsoffat(32%comparedtobaseline),andlostmoreintraabdominalfat(51%)thansubcutaneousfat(34%)inpercentageterms.Afterthe3monthdiet,theyhada3monthweightstabilizationperiodduringwhichsolidfoodwasconsumedandweightmaintained.Thankstothisintervention,insulinsensitivitydoubledcomparedtobaseline.[11]Inanotherstudy,9obesemen(BMIover30)underwenta1yearweightlossprogramandlostmorethan4kg(8.8pounds)ofbodyweight;meanweightlosswas10.8%.Fastinginsulinlevelsfellby59%,andmeasuresofinsulinsensitivityincreasedsignificantly.[12]Thesameresearchersconductedasimilarstudywithobesewomen.ThirtyfiveobesewomenwithBMIgreaterthan30underwenta1yearweightlossprogramandlostmorethan4kg(8.8pounds)ofbodyweight,withameanweightlossof9.6%.Measuresofinsulinresistanceweremarkedlyimproved[13].Fourmajorexperimentalstudieshavetestedtheassertionthatdiabetescanbepreventedordelayedbylifestylechanges,asreviewedbyDeborahL.Burnetandcolleaguesin[14].Theyconcludedthatstrongevidenceexistsforthepreventionordelayoftype2diabetesthroughlifestylechangesandthatlifestylechangesweremoreeffectivethanmedicationforpreventingtype2diabetesandshouldbeusedasafirstlinestrategy.Eventhoughthesetrialswerenotpurelyweightlossbasedtheyalsoincludedincreasedexerciseandchangeindietcompositionoverweightindividualswereencouragedtoloseweight.The4studieswerecarriedoutinindividualsathighriskfordevelopingdiabetes,andriskreductionsfordevelopingtype2diabetesrangedfrom3163%over36years,eventhoughweightlosswasquitemodest.Althoughwedontknowforsurehowmuchoftheresultswerethankstofatloss,ascomparedtoexerciseorimproveddietquality,itishighlylikelythatlossoffatwasanimportantcontributingfactor.Asstatedbytheauthorsin[14]Theoverallgoalfordiabetespreventionistoreachandmaintainanactive,healthyweightwithatendencytowardahypocaloricdiet[adietthatsupplieslesscaloriesthanyouuse].


26

Fatlossshouldalsohelpthosemetabolicallyobese,normalweightindividuals,whoalreadyhavealowBMI(2025),butmorethanlikelyhaveahighproportionofabdominalfat.Indeed,IwasoneofthemandthemostimportantinterventionIusedpersonallyagainstmyinsulinresistancewasfatloss.Itmaybehelpfulifyoucantestyourinsulinsensitivity(byoralglucosetolerancetestorHOMAIR)beforeandafter5%ormorefatlosstoseeifyouaremakingprogress.Butifyouhaveinsulinresistance,youwillalmostcertainlybemakingprogressbylosingfat,sotrackinginsulinsensitivitymayberedundant.

Can central fat be specifically targeted for fat loss? Asyoulosetotalfat,youwilllosecentralfataswell.Losingtotalfatandcentralfatarebothbeneficial.Onethingthatmayhelpinlosingalargerproportionofcentralfatisaerobicexercise[5][23],addressedinthechapteronexerciseandinsulinresistance.

Can you have too little body fat? Generallyspeaking,aslongasyourfatlossesareaccompaniedbyimprovementsininsulinsensitivity,youcancontinuelosingfat.However,bodyfatisnotcompletelywithoutvalue,anditISpossibletogotoolow.Menshouldprobablynotbeleanerthan5%bodyfatinthelongterm,whilethefigureforwomenmaybe12%orso.Buttheseareverylowlevels,thatmostpeopleneverachieve.

Fat loss tips AcompleteguidetoweightlossisavailableinappendixA.Herearesomeshorttipstogetyoustarted:

Createacaloriedeficit.Regardlesswhichdietcompositionyouchoose(highcarb,lowcarb,mixed,vegetarian,Mediterraneanetc.)youabsolutelymustcreateacaloriedeficitifyouaregoingtolosefat.Yousimplymustconsumelesscaloriesthanyouburn.

Countingcaloriesisnotabadidea,althoughnotarequirementtofatloss.Learnhowtodothisifyouresoinclined.Itsagoodskilltoknow,anyhow.

Dontlosemorethanaround2pounds(1.0kg)perweek.Losingfasterthanthatincreasestheriskofdevelopinggallstones,rampantmuscleloss,bonedensityloss,reactivebingeeating,slowedmetabolism(reducedcalorieburn)andnutrientdeficienciesbecauseyoueatsolittlefood.

Aimforadailycaloriedeficitinthe3001000calorierange.Thehigherendoftherangeisreservedformoreoverweight/obesepeople.Theleaneryouget,orthesmallerpersonyouare,thesloweryouwanttogotopreservemusclemassandmetabolism.


27

Eatalotofprotein.Notonlyisitmoresatiating,itisalsomusclesparing.Oneofyourgoalswhilelosingweightshouldbetopreservemusclemassandlosefatspecifically.Musclemassisnotonlypleasingtotheeye,itisusefulforeverydaytasksandthemoremusclemassyouhavethemorecaloriesyouwillburnperdaybecausemuscleburnsmorecaloriesthanfat,evenwhenyoudontusethemuscles.Losingalotofmusclemasswillslaughteryourcalorieexpenditure,makingithardertomaintainalowamountofbodyfat.Somusclepreservationiskey.

Eataround2gramsofproteinperdayperkgofbodyweight,or1gramofproteinperdayperpoundofbodyweight.Ifyouareoverweightorobese,youcanadjustthesefiguresdownwardabit,i.e.eatabitlessprotein.

Strengthtrainingwillhelpyoupreservemusclemasswhilelosingweight,increaseyourcalorieburn,andwillimproveyourinsulinsensitivity.Thisiscoveredfurtherinthechapteronexercise.

Aerobictraining.Thisreferstoendurancetraining,i.e.activitiesthatgetyourheartrateupandmaintainedforagoodwhile.Examplesincludebriskwalking,running,cycling,swimming,dancingetc.Intervaltrainingisnotabadthingtothrowintothemix,either.Thisiscoveredmoreinthechapteronexercise.Thereareindicationsthatexercisemayhelpwithlossofintraabdominalfatspecifically[5].Inanycase,thebenefitsofaerobicexercise,especiallyforinsulinresistantindividuals,aretoonumeroustomention.Youshoulddothisregularly,period.

Eatmorefiberandfat.Thesenutrientswilltypicallymakeyoufeelmoresatiatedcomparedtocarbohydrates,althoughIdonotthinkthatcarbsareevil.Thiswillbecoveredmoreinthechapterondiet.

Avoidsimplecarbohydratesandjunkfood.Simplysaynoto(orgreatlyreduce)sugarladenpseudofoodsandindustriallyprocessedjunk.YouknowwhatImtalkingabout:sodas,pizza,Frenchfries,snacks,chocolate(exceptdarkchocolate),sweets,icecreametc.etc.etc.adinfinitum,aswellaspremadefrozendinnersetc.

Cookhealthymealswithrealingredientsfromscratch.Moreinfointhechapterondiet.

Avoidrestaurants.Peoplewhoeatalotatrestaurantsaretypicallyfatterthanthosewhodont.Cookfoodinadvanceandbringtoworkifyouhaveto.

Dietresponsibly.Makesureyougetenoughvitaminsandminerals,proteinandomega3fatsetc.Thelessyoueatthebetteryourdietaryqualityshouldbe,soyourecertaintogetenoughmicronutrients.Avoidcrazyfaddiets,fasting,dietsbasedonmealreplacementpowdersetc.

Summary Most,butnotall,insulinresistantpeopleareoverweight/obese.Beingoverweight/obeseincreasestheriskthatapersonisinsulinresistant.Ifyoureoverweight/obeseandinsulinresistant,losingfatwillprobablybethesinglemostimportantthingyoucandotoincreaseyourinsulinsensitivity.


28

Themostdangerouskindoffatdistributionisabdominalfat,specificallyintraabdominalfat.Menhavemoreintraabdominalfatthanwomen,andsomelifestylefactorscanaffectbodyfatdistribution,althoughalotseemstobedeterminedbyhormonesandgenes.Thereexistsinthegeneralpopulationquitealotofpeoplewhoaremetabolicallyobese,normalweight,characterizedbyaBMIinthe2027range,i.e.normalorclosetonormalweightbystandardmeasures,butsufferingfrominsulinresistance,probablycausedbyalargeproportionofabdominalfat.Suggestionsforidentifyingwhetheryouaresuchapersonhavebeenpresentedinthischapter.Thisisrarelyanapparentconditionandmustbescreenedforcarefully.Infact,Iliketocallithiddenobesity.Payspecialattentiontotheexistenceofexcessintraabdominalfatthatyoumayhave.Waisttohipratioandwaistcircumferencehavebeendiscussedandthese,togetherwithBMI,arentreallythebestmeasuresofabdominalobesity,andcantrickapersonintobelievingthatheorshedoesnothaveexcessfat,whiletheoppositemaybetrue.Ontheotherhand,CTscan,MRIorultrasoundcanidentifythepresenceofanunusuallyhighamountofintraabdominalfat.Alloverweightandmetabolicallyobese,normalweightpeopleshouldgoonafatlossprogramconsistingofacaloriedeficitcreatedbylimitingcalorieconsumptiontogetherwithstrengthtrainingandaerobicexercise.Fatlossshouldcontinueaslongasneededtorestoregoodinsulinsensitivity,butifbodyfatlevelsof5%and12%formenandwomen,respectively,areachievedandIRpersists,theproblemmaybesomethingelse.Fatloss,whiletypicallythemainstrategyforimprovinginsulinsensitivity,isnottheonlystrategyandtheothermethodsinthisbookshouldalsobeimplementedorconsidered.ItsworthrepeatingthattheretrulyareothercausesofIRexceptexcessfat,aswillbeexploredfurtherinthisbook.Noteveryinsulinresistantindividualneedstodiet.Iwaspersonallyoneofthosemetabolicallyobesenormalweightindividuals,andwentonafatlossprogramuntilIwasveryleanwhichgreatlyenhancedmyinsulinsensitivityandreversedmyinsulinresistance(withhelpfromtheotherstrategiesinthisbookaswell).


29

Chapter 2 Iron and Insulin

Resistance

Thereisalotofevidencethatbodyironstores,inotherwordshowmuchironyouhavestoredinyourbody,areassociatedwithinsulinresistanceandtype2diabetes[7].Statedanotherway,thehighertheironlevels,thegreaterapersonsriskofdevelopingdiabetesandinsulinresistance.Theproblemsseemtostartevenatironlevelsconsideredbymostdoctorstobenormal.InthewordsofresearcherJosManuelFernndezRealandcolleagues:Itisincreasinglyrecognizedthatironinfluencesglucose[bloodsugar]metabolism,evenintheabsenceofsignificantironoverload.[emphasisadded][13]Oneproblemwhenstudyingthepotentiallinkbetweenironandinsulinresistanceisthedifferentwaysofmeasuringbodyironstores.Bodyironstoresareusuallymeasuredbythebloodtestserumferritin(SF)whichmeasurestheamountofferritinintheserum.Ferritinisastorageproteinforironatoms.Itisagoodindicatorofbodyironstoresundermostcircumstancesbutnotall.Forexample,ifchronicdiseaseorinflammationispresent,serumferritincanbeelevatedevenwhentotalironlevelsarenot.Dependingonwhichagencyyouask,irondeficiencyasmeasuredbySF(irondeficiencycanalsobemeasuredbyotherbloodtests)isbelowthe1530ng/mlrange.Normallevelsareusuallyconsideredbetween30and300but,aswewillsee,itseemsthatironcancauseinsulinresistanceevenatanySFlevelabove40,eventhoughmostdoctorswouldconsiderthatinthecompletelynormalrange.InalargesampleofGermanmenandwomen,peoplewithhigherserumferritinlevelshadagreaternumberofinsulinresistanceelements.Inthisstudy,insulinresistanceelementsweredefinedas:BMIover25,diagnoseddiabetes,hightotalcholesterol,lowHDLcholesterol[goodcholesterol],highbloodpressure.[4]Prediabeticshavealsobeenshowntohavehigherserumferritinthanthosewithnormalbloodsugarcontrol.Higherserumferritinhasbeenfoundtocorrespondwithhigherfastingbloodsugar,higherbloodpressure,highercholesterolandhighertriglycerides.Inonestudy,thosewithhighferritinhad3timestheriskofhavingprediabetes.[6]


30

Vegetarians have lower insulin resistance Ithasalsobeenshownthatvegetarianshaveincreasedinsulinsensitivityandlowerironstorescomparedtomeateaters[14].Thirtyleanlactoovovegetarians,definedasthosewhohadconsumednomeatfortheprevious5years,werecomparedto30leanmeateaters,definedasthosewhohadreportedeatingmeatatleastoncedailyfortheprevious5years.Itwasfoundthatmeateatershadtwicethebodyironstoresoflactoovovegetarians(asindicatedbyserumferritinlevels),andhadamuchhigher(68%)steadystateplasmaglucoselevel,averygoodindicatorofinsulinresistance.Inotherwords,themeateatershadalothigherironstoresandalotmoreinsulinresistance.Totestwhetherornotitwasthelowerironstatusthatgrantedincreasedinsulinsensitivitytothevegetarians,sixofthemalemeateaterswereselectedforironreductionbyphlebotomy(bloodletting).Thesixmeateatershadaninitialaverageserumferritinlevelof85andthiswasreducedto27afterphlebotomy.Steadystateplasmaglucosewas41%lowerafterphlebotomy,i.e.theyweremuchlessinsulinresistantafterironreduction.

Blood donors have lower insulin resistance Frequentblooddonationshavebeenshowntobeaprotectivefactoragainstthedevelopmentoftype2diabetes[16].Menwhodonatebloodfrequentlyhavelowerbodyironstores(asmeasuredbyserumferritin)andenhancedinsulinsensitivitycomparedtononblooddonors[5].Inonestudy,theseresultswereprimarilyfoundinthosewhodonatedbloodatleast2timestheprevious5years,andhighernumberofblooddonationscorrespondedtohigherinsulinsensitivity,indicatingacauseandeffectrelationship.However,itmustalsobeconsideredthatonlyhealthypeopleareallowedtodonateblood,whichcouldmeanthatblooddonorsareonaveragehealthierthantherestofthepopulationandthushavebetterinsulinsensitivity.However,itstilldoesntexplainwhythosewhodonatedfrequentlyhadbetterinsulinsensitivitythannonfrequentdonors.Theblooddonorsinthisstudy[5]hadaverageserumferritinlevelsof101vs.162amongnonblooddonors.BothofthoselevelsareunnecessarilyhighandassociatedwithincreasedriskofIR.Inanotherrecentstudy[15],21highfrequencyblooddonors(morethaneightdonationsinthepast2years)werecomparedto21lowfrequencyblooddonors(12donationsinthepast2years)andtheirserumferritinwas23vs.36respectively.Nodifferencewasfoundininsulinsensitivityasmeasuredbyoralglucosetolerancetest(OGTT)betweenthetwogroups.Norelationshipwasfoundbetweeninsulinsensitivityandnumberofblooddonationsorserumferritin,either.ApproximatelyonethirdoftheparticipantshadbloodsugarproblemsasevidencedbyabnormalOGTTresults,despiteverylowserumferritinlevels.[15]


31

Inmyview,thismeansthat:

bodyironisnottheonlydeterminantofbloodsugarregulation;itispossibletohavebloodsugarproblemsandinsulinresistancedespitelownormalironlevels

Nofurthereffectofironreductiononinsulinsensitivityisseenbelowserumferritinlevelsof36(inthisstudy),soitmaybeunnecessarytolowerserumferritinmuchbelow40.

Lookingatmorestudies,inanationallyrepresentativesampleofmenandpostmenopausalwomen,amodestassociationbetweenserumferritinlevelsandperipheralarterialdiseasewasfound.PADisakindofbloodvesselailment.Theassociationwasgreaterinthosewithhighcholesterollevels.[2]Onerecentstudyfoundthatpeoplewiththehighestserumferritinlevelshada74%higherriskofdevelopingdiabetestype2,butthisfindingwasexplainedbyotherfactors[10].Theresearchershypothesizedthat,inthisstudy,thehigherserumferritinlevelsseeninthosewhowentontodevelopdiabetesmayhavebeenaresultofthecondition,sincediseasestatescancauseanelevationofserumferritinevenwhennoironoverloadexists.Insuchcases,serumferritindoesnotaccuratelyreflectbodyironstores.Inanotherstudyonmales,thosewiththehighestSFconcentrationshada70%greaterriskofdevelopingdiabetescomparedtothosewiththelowestSFconcentrations[27].HigherSFwasassociatedwithhigherbloodsugarandinsulinlevels,i.e.insulinresistance,inastudyof1013Finnishmen[24].Inhealthypeople(freeofdisease),serumferritinwenthandinhandwithinsulinresistance[26]andinthesamestudy,italsowenthandinhandwithdiabetesseverity(indicatedbyHbA1c)intype2diabetics.Finnishmenwithhighstoresofironhavebeenfoundtobe2.4timesmorelikelytodevelopdiabetesthanmenwithlowerstoresofiron[25].Elevatedserumferritinhasbeenfoundtobeassociatedwithinsulinresistanceandfattyliverinpatientswithnoothersignofironoverload[1].

Iron and IR are associated, but does iron reduction actually help? Theideathatreducingbodyironstoresfromhighornormaltoneardeficientwouldimproveinsulinsensitivityorothermarkersofbloodsugarcontrolhasbeentested.Inaspecialstrainofmice,thesocalledobeseob/oblep/mouse,whichisverypronetodevelopingdiabetes,anironrestricteddietwasfoundtoprotectagainstthedevelopmentofdiabetesandinsulinresistance[20].Lowertriglycerideswerealsoseeninthemiceontheironrestricteddiet.Thisdietwashighenoughinirontonotleadtoanemia.Theresultsseemedtobethankstoimprovedpancreaticbetacellfunction(i.e.insulinsecretion)andinsulinsensitivity.Whenmiceinitiallyfedtheironrestricteddietwereswitchedtothehigherirondiet,thepositiveresultsweregraduallylost.Luckily,wealsohaveexperimentaldataonironreductionsinhumans.


32

Asmallstudy[17]performedon10healthyblooddonors,testedtheeffectonbloodsugarandinsulinconcentrationsfourweeksafterasinglebloodwithdrawalof500ml.Serumferritinlevelswerecutinhalf,from75to38andconcentrationsofinsulinandbloodsugar2hoursafteranOGTTwerereducedby37%and19%respectively.Thisfindingshowsthatevenblooddonorscanstillhaveexcessiveironstores,that75serumferritinmaystillbeexcessivelyhigh,andthatreductionofironstoresimprovesbloodsugarandinsulin.Themostlikelyexplanationoftheseresultsisthatreducedironlevelsledtoreducedinsulinresistanceandperhapsimprovedbetacellfunction.In2002,astudy[8]wascarriedouton31carbohydrateintolerantpatientswithnormalironstoresnotclosetodeficiency.Afterironreductionbybloodlettingtoironlevelsclosetodeficiency,tolevelscommonlyseeninpremenopausalwomen,thefollowingimprovementswerenotedinthepatients:

IncreasedHDLcholesterol(thegoodcholesterol) Reducedbloodpressure ReducedtotalandLDL(bad)cholesterol Reducedtriglycerides,reducedfibrinogen ReducedglucoseandinsulinresponsestoOGTT(mostlikelythankstoreducedinsulin

resistance)Thesearegreatresultsanditdoesntgetmuchbetterthanthat.Aftera6monthperiodofironrepletion,duringwhichironstoreswereincreasedagain,theseimprovementswerelargelylost.Asalreadynoted,bigimprovementsininsulinsensitivitywereseenwhenbodyironstoresoflean,healthymeateaterswerereducedtothoseofvegetarians[5].Bloodlettingshouldalsohelpthosealreadysufferingfromtype2diabetes,butresponseshavebeensomewhatmixed.In1994,22type2diabeticsdonatedseveralunitsofblood(oneunitis450ml)resultinginasignificantdecreaseofserumglucose[bloodsugar],cholesterol,triglyceride,andapoproteinBconcentration.Theseresultswerenotseeninthenondonatingcontrolgroup,exceptadecreaseofbloodsugar.[12]Allthesechangesarebeneficialfromahealthperspective.Ina2002study,ironreductionbyphlebotomyof28maletype2diabeticsresultedinreducedHbA1c(amarkerofdiabetesseverity)from6.27%to5.66%wherelowerisbetter.Theseresultswereachievedbyextracting500ml(quart)ofblood3timesat2weekintervals.However,inthisstudyserumferritinwasonlyreducedfrom460initiallyto232aftertreatment.232isstillmuch,muchhigherthanthelevelsseeninpremenopausalwomenorvegetarians,soevengreaterresultsmaypossiblyhavebeenachievedbyfurtherironreduction.[9]In1989,PaulCutler,M.D.,[18]hadgoodresultswhenusingdeferoxaminetotreattype2diabeticswithhighironstores.Deferoxamineisanironchelatorusedintravenously;itbindstoironinsidethebodyandtransportsitoutofthebodythusloweringironstores.Nine


33

diabeticpatientswithserumferritinlevelsbetween343and824weretreatedtwiceweeklywithdeferoxamineuntilnormalferritinlevelswereseen,i.e.below330.MeanSFlevelsbeforetreatmentwere595whichdroppedto295aftertreatment.Fastingbloodsugar,HbA1candfastingtriglyceridesdroppedsignificantlyaftertreatmentandeightofninepatientsstoppedtakingdiabetesmedications.Inacontrolgroupconsistingof8normalirontype2diabetics,serumferritinwasalsoreducedwithdeferoxaminefrom196to140,butthisproducednochangeincholesterol,HbA1cortriglycerides,buttherewasatrendtowardsreducedbloodsugar.Thelackoflargetreatmenteffectsinthecontrolgroupwasprobablybecausetheirdiabeteswasntassevere(asmeasuredbycholesterol,triglyceridesandHbA1canddiabetesmedications),andthetreatmentonlyreducedironlevelsmodestly.Probably,inmyopinion,agreaterreductioninserumferritinwouldhaveproducedbetterresults.Anothergroupofresearcherstriedin1993toreplicateCutlersfindings,usingthesameprocedure[19].However,theyfoundnoevidencethatironreductionhadanyrelevantbeneficialeffectsintype2diabeticsexceptasmallreductionofHbA1c,amarkerofdiabetesseverity.Thestudieswerealmostidentical.Howeverinthe1993studytheserumferritinwasntquiteashighinitiallyandwasntreducedasmuchinpercentageterms.Whetherthisexplainswhyironreductiondidntworkinthesepatientsisuncertain.Inpatientswithnonalcoholicfattyliverdisease,anailmentcloselyassociatedwithinsulinresistanceandconsideredbysomeexpertstobeapartofthemetabolicsyndrome,bloodlettinghasalsoprovenbeneficial.SixtyfourpatientswithNAFLDwhohadundergone4monthsofnutritionalcounseling,i.e.dietaryrecommendations,andstillhadsignsofNAFLDorelevatediron(asmeasuredbyserumferritin)wentthroughirondepletionbybloodletting,whilestillfollowingdietaryrecommendationsforNAFLD.Whencomparedto64NAFLDpatientswhoreceivedonlydietarycounselingforthesametimeperiod,theirondepletedpatientshadsignificantlylowerinsulinresistance.Moreover,ironreductionwasmorebeneficialinpatientswiththehighestinitialironlevels(indicatedbyserumferritin)indicatinggreaterbenefitofloweringironamongthosewiththehighestironlevels.Interestingly,inthedietonlygroupserumferritinlevelsdeclinedaswell.PerhapstheironreducingeffectofthedietiswhatmakesiteffectiveagainstNAFLD.Nevertheless,ironreduction+dietwasmoreeffectivethandietalone.[11]

How does iron cause insulin resistance? Ironcausesinsulinresistanceviaanumberofmechanisms,thatmaynotbefullyunderstood.Intheirreviewofthesubject,FernndezRealandcolleagues[13]explainedthat:

Normally,insulinsignalsthelivertoslowdownorturnofftheliversproductionofnewbloodsugar(gluconeogenesis).However,ironinterfereswiththissignallingwhichleadstohighbloodsugar.


34

Normally,theliverworksonreducingexcessiveinsulinlevels.However,ironinterfereswiththisprocessalso,leadingtohighinsulinlevels.

Highinsulinlevels,inturn,increaseabsorptionofironfromthediet,causingaviciouscircle.

Excessiveironlevelscancausetheproductionofsocalledreactiveoxygenspeciesthatcancausecelltissuedamageand,byextension,contributetocomplicationsoftype2diabetes.

ItalsoseemsthatironcontributestoelevationsofHbA1cduetoincreasedreactiveoxygenspecies.

ResearcherFernndezRealandcolleaguesstate[5]that:Reactiveoxygenspeciesinterferewithinsulinsignalingatvariouslevels,impairinginsulinuptakethroughadirecteffectoninsulinreceptorfunction.Thiswouldessentiallycauseinsulinresistance.TheabovestatementsareechoedbySwaminathanandcolleagues[3]who,intheir2007reviewentitledTheRoleofIroninDiabetesandItsComplications,statethatironmaycausetype2diabetesthrough3keymechanisms,namely:

Insulindeficiency(i.e.impairedinsulinsecretionbythepancreas) Insulinresistance Liverdysfunction

Insulindeficiency,theyreport,maymaterializeduetoironsproductionofreactiveoxygenspeciesthatinturnattackspancreaticbetacellsleadingtotheirdysfunctionanddeath,asfoundinamousestudy.Impairedbetacellfunctionwouldleadtoreducedproductionandsecretionofinsulin,causinghighbloodsugaranddiabetes.

Who should lower their iron and how low? Theideallevelofbodyironstoresis:justenough,butnomore.Aswehaveseen,evenbodyironstoresconsiderednormalbymostdoctorscanbeacauseofinsulinresistance.Sinceirondeficiencyasmeasuredbyserumferritinisusuallydefinedaslevelsbelow30,asafelevelwouldbearound40,i.e.nearirondeficiency(NID).Thiswouldputanindividualclosetothoselevelsseeninvegetariansandfrequentblooddonors,groupsthathavelowerratesoninsulinresistance.Asmentioned[15],SFbelow36doesnotseemtobeassociatedwithfurtherimprovementsininsulinsensitivity.Thisisalowriskstrategy;iftheresearchlinkingironstorestoinsulinresistanceultimatelyprovestobewrong,youhavelostnothingbecauseyoustillhavemorethanenoughiron.If,ontheotherhand,irondoesindeedcauseinsulinresistanceandyouhaveexcessiveironlevels,youwillpayahighpricefordoingnothing.EvenaclosetodeficientSFlevelof40shouldbesufficientforathletes.Forsedentaryfolks,serumferritinmayevenbereducedto25,asrecommendedbyE.D.WeinbergoftheIronDisordersInstituteinhisbookExposingTheHiddenDangersofIron.


35

Oneconfoundingfactor,though,isthatserumferritinissometimeselevateddespitelowbodyironstores.Thiseffectcanbeseeninsomeinflammatorystates.Therefore,youshouldalwaysconsultwithyourdoctortodeterminewhetheryouareagoodcandidateforironreduction,i.e.verifythatyoutrulyhavehighornormalasopposedtoneardeficientironstores.Agoodindicationthatyourironlevelstrulyareexcessiveandthatyoureagoodcandidateforironreductiontothe2540SFlevelisthecoexistenceofserumferritinabove40,normalorelevatedtransferrinsaturationandanyofthefollowing:

Highbloodpressure LowHDLcholesterol Hightriglycerides Highfastingbloodsugar Highfastinginsulinlevels InsulinresistanceasmeasuredbyHOMAIRorsimilar Elevatedpostmealbloodsugarlevels(asmeasuredbyOGTT) Elevatedpostmealinsulinlevels(asmeasuredbyOGTT) Fattyliverdisease Type2diabetesorprediabetes OthersignsofIR

Whenhighironstorescoexistwithinsulinresistance,asindicatedbythelistabove,ironreductionshouldprovemostbeneficial,andwouldlikelyimprovemanyoftheaboveconditions,too[8].Thehigheryourironlevelsare,themoreimportantitistolowerthem.Therefore,ifyoutakemedicationsfortheaboveconditions,youandyourdoctorshouldmonitorthemandadjust(reduce)medicationsaccordingly.Dontbesurprisedifotherailmentsthatyoumayhavearereducedorvanishasyoureduceyourironstores.Theminimumlevelforsedentarypeople(SF)shouldbearound25,whileifyourehighlyphysicallyactive,SFlevelsupto50areprobablyallrightandshouldprobablynotgomuchbelow35.Anythingabove50ng/mlSFisexcessiveandshouldbelowered,exceptinsomerarecircumstanceswhereSFmaybeelevatedeventhoughbodyironstoresarenotexcessive.Alwaysdiscussironreductionwithaknowledgeabledoctortomakesureitsnotharmfultoyou.

Iron reduction and other markers of health/disease AsexplainedinhisbookTheIronFactorofAgingWhyDoAmericansAgeFaster?,FrancescoS.FacchiniM.D.,Ph.D.describeshowoxidationifoneofthemaincausesofagerelateddiseases(diabetes,heartdisease,canceretc.),andhowoxidationisacceleratedbythepresenceofexcessbodyiron.


36

Onthesamenote,DouglasB.Kellinhisextremelycomprehensive2008article[23]onironandinflammatoryanddegenerativediseasesmakesthecaseforironexcessbeingimplicatedinthefollowingconditions:

preeclampsia Diabetes Metabolicsyndrome Obesity Heartfailure Atherosclerosis Alzheimers Parkinsons Multiplesclerosis Friedrichsataxia ALS/LouGehrigdisease Rheumatoidarthritis Asthma Chronicobstructivepulmonarydisease(COPD) Psoriasis Gout Renal[kidneyproblems] Alcoholicandotherliverdiseases Cancer Malaria Antimicrobials SepsisandSIRS Aging Longevity Frailty Lupus/SLE Inflammatoryboweldisease

Thatsnottosaythatallthoseailmentswillbecuredorevenimprovedbyironreduction.Butironreductionmayhelppreventthedevelopmentofthem,andinmanycasesimprovesymptomsoncetheyhavemanifested.

How to reduce iron levels Principally,thereare3waystoreduceironstores:

1. Reduceyourintakeofiron2. Increaseyourlossesofiron3. Both


37

Adultsloseabitofiron(11.5milligrams)perdaythroughurine,feces,perspirationbloodlossfrommenstruationetc.,soanytimeyouabsorblessironthanthat(fromdiet,beverages,inhalationandthroughyourskin),yourironlevelswilldecline.Hence,itisoftenpossibletoreduceyourironlevelsjustbyreducingyourironintake.Thefastestwaytoreduceiron,though,isbyreducingironintakeandincreasingironlosses.Thereareseveralstrategiesyoucanemploytoreduceironlevels.Briefly,theyinclude:

Vegetariandietordietlowinavailableiron Blooddonation Phlebotomy(bloodletting) Exercise Medicalironchelators(drugsthatreduceiron) IP6(nonprescription,naturalsupplementthatreducesironlevels)

Letsfirstlookathowtoreduceyourintakeofiron.

LowironavailabledietIgenerallydonotrecommendavegetariandiet.Norisitnecessarytoreduceironlevels.Adheringtoadietlowinavailableironisthemainwaytoreduceironabsorption.Heresasummaryofstrategiesthatwouldbehelpful:

Replaceredmeatwithpoultryorfishoreggs.Thisisthemostimportantstep. Donteattoomuchwildmeat,sincetheycontainmuchmoreironthandofarm

raisedanimals.Buyhighquality,pasturefedmeatwheneverpossible,eventhoughthisisnotnecessaryfromanironreductionpointofview.

Discontinueanyironsupplementsyoutake,includinganyironinyourmultivitamin/multimineraltablets.

DonttakevitaminCsupplementswithmeals.Takethembetweenmealsifyouneedthem.VitaminCincreasesabsorptionofironwhenconsumedwithmeals.

Drinkredwineortea(withoutsugar)withmealswheneverpossible.Thesedrinkscontaincompounds(polyphenols,tannins,respectively)thatreduceabsorptionofironfromthatmeal.

Ifyouaddfattoyourmeal,useextravirginoliveoil.Itcontainscompoundsknownaspolyphenolsthatreduceabsorptionofironfromthatmeal.

Anythingcontainingcalcium,suchasmilkandcheese,reducesabsorptionofironfromotherfoodstuffseatenatthesametime.

Eggs(seeabovepoint) Dontdrinksodasoranythingelsethatisacidicwithmeals.Allsodasareacidicand

acidfoodsanddrinkswillincreaseabsorptionofironwhentakenwithameal.Infact,itsbetternottodrinksodasatall(surprise,surprise).

Dontdrinkfruitjuiceswithmeals.TheirvitaminCandsugarcontentwillincreaseironabsorption.Infact,itsbetternottodrinkfruitjuiceatall.

Dontdrinkalcoholwithmeals(exceptredwine).Itwillincreaseabsorptionofironfrommeals,undermostcircumstances.


38

Whatkindofresultscanyouexpectfromsuchadietaryintervention?In2003,alowironavailabledietwasgivento191type2diabetics[21]inthehopesthatitwouldslowtheprogressionofdiabeticnephropathy,i.e.kidneydiseasecommonlyseenindiabetics,comparedtoanormalproteinrestricteddiet.Theexperimentaldiethad3specificcharacteristics1)lowinavailableiron2)carbohydraterestricted3)polyphenolenriched.Onthisdiet,serumferritinlevelsfellfrom301to36over2years.After1year,SFlevelshaddeclinedtoabout125.Specificcharacteristicsofthisdietincluded:

50%reductionofcarbohydratesfrompreviouslevelsofintake Redmeatwasreplacedwithfish,eggs,poultry,dairyandsoy[note:Idont

recommendsoy] Eliminationofallbeveragesexcepttea,waterandredwine.Milkwasrecommended

forbreakfast.Teawashighlyrecommended.Nomorethan150mlofredwinewithlunchandnomorethan150mlofredwinewithdinner.Onlywaterallowedoutsideofmealtimes.

ExclusiveuseofpolyphenolenrichedextravirginoliveoilforbothdressingandfryingWithregardstoiron,thecarbohydraterestrictionwasprobablyunimportant.Itwasincludedinthedietforotherreasons.Wecanseethatsuchadiettendedtostabilizeironstoresaroundoptimallevels(SF:36),nearirondeficiency,whilenotincreasingratesofanemiainthetreatmentgroup[21].Alsoofinterest,thedietdescribedabovedidimprovekidneyandtotalsurvivalratesby4050%comparedtoastandardproteinrestricteddiet.NotethatImnotrecommendingalowironavailabledietperse;Iammerelymentioningitasonetoolthatcanhelpyouloweryourironlevels.Byaddingotherstrategies,youcancontinueeatingredmeatifthatswhatyouwant.

ExerciseExerciseincreaseslossesofiron.Maleenduranceathleteslosearound1.75mgofirondaily,comparedto1mgcitedforaveragemales,whilefemaleenduranceathletesloseabout2.3mgofirondailycomparedto1.4mg/dayforotherfemales[22].Thegreaterironlossesinfemalesareduetomenstruation.Lowironismorecommoninthosewithhigherleveloffitness,andhighironislesscommoninthesamegroup[27].Themoreyouexercise,themoreironyoulose.Thisisonestrategythatcanbeusedtohelpreduceironlevels.


39

Phlebotomy(bloodletting)Onewaytoloweryourironlevelsistodiscussphlebotomywithyourmedicaldoctor.Awithdrawalof500mltypicallyresultsinadropofserumferritinofaround30points.Thesecantypicallybedoneevery34weeks,sometimesmoreoften.

BlooddonationIfyourmedicaldoctorwonthelpyouwithphlebotomy,youmaylookintoblooddonationasanalternativestrategy.Malesareusuallyallowedtodonateblood4timesperyear,whilefemalesmaydonateblood3timesperyear.Thismayormaynotbeenoughasastandalonetreatmenttoreduceyourirontoappropriatelevels.Itcancertainlybeanaid,sincedonating1unitofblood(450ml)wouldreduceSFanaverageofalmost30points.Blooddonationfacilitiestypicallydonottestyourserumferritin,soyoustillhavetogetseparatebloodteststokeepaneyeonyourserumferritinlevels.

IP6IP6isaninterestingsupplement.Alsoknownasphyticacid,phytate,inositol6phosphateandinositolhexaphosphate,itisanantinutrientratherthananutrient.Itisderivedfromnaturalplantsources.Indeed,itisfoundinmanyofthemostcommonfoodstuffsweeat,suchaswholegrainsandunrefinedrice.Forourpurposes,itisusedtoreducebodyironstores.IP6,whenconsumedorally,bindstocertainsubstancesinsidethebodyandescortsthemout(throughtheurine).Theusefulnessofthissupplementliesinitsabilitytobindtoironandformacompoundwhichisthenlostthroughtheurine.Inotherwords,IP6canbeusedtoreduceironstores.ThedownsidetousingIP6isthatiscanalsobindtoothermineralssuchasmagnesium,zincandselenium.Itcanalsointerferewithabsorptionofnutrientsfromfoodandbeverages,aswellasmedications.Thereforeitisbesttakenin1singledoseperday,firstthinginthemorningonanemptystomachswallowedonlywithtapwater.Thereafter,itsbesttowaitonetothreehours(closerto23hoursisbetter)beforeeatingordrinkinganything,whiletheIP6doesitswork.IP6,asstated,actuallyexistsnaturallyinunrefinedgrains,beansandnuts,buttolowerironstoresyouneedtousepurifiedIP6asasupplement.IhavetestedJarrowFormulasIP6anditworks.ThereareotherIP6productsonthemarketthatalsowork.WhiletakingIP6,itisrecommendedtoalsotakeextrazinc,magnesiumandseleniumbutdoNOTtakethoseatthesametimeofdayasIP6.OnlytakeIP6IFyouneedtobringyourserumferritinlevelsdown.IhavepersonallyusedIP6tobringdownmyserumferritinfromover100to40,inthemannerdescribedabove.IfyouchoosetoloweryourironstoreswithIP6,youneedtokeepacloseeyeonyourserumferritinlevels(thesamethingholdstrueforanyironreductionprocedure).Suggesteddose:30005000mgperdayuntiloptimalSFisachieved.


40

PuttingittogetherForalloftheaboveironreducingstrategies,youllneedtokeepaneyeonyourserumferritinlevels.Ifyourferritinisveryhigh,youcouldimplementanaggressiveprogramofblooddonation/phlebotomy,IP6and,exerciseandlowavailableirondietforawhile.Butthecloseroptimalironlevelsyouare,themorecarefulyouhavetobesoyoudontlowerthemtoofar,althoughthisisusuallynotaproblembecauseironabsorptionfromdietautomaticallyincreasesatlowbodyironlevels.Nevertheless,aggressiveironreductioncanofcourseleadtoirondeficiency.Thereisnobeststrategy,butalowironavailabledietseemstostabilizeironintherightrange.However,ifyouexercisealot,alowironavailabledietmayleadtoirondeficiency.Sowithlargevolumesofexercise,youmayhavetoeatmoreironrichanimalfoods.Acombinationoftheabovestrategiescoupledwithregularserumferritinbloodtestswillgetyourironlevelsintotherightrangeandkeepthemthere.Ifyouwanttolearnmoreaboutironlowering,orneedevidencetoconvinceyourmedicaldoctororyourself,readExposingtheHiddenDangersofIro

insulin resistance solution

Documents

inwh of contents foreword