Week11–DietandExerciseandCVDà2particularlyimportantcholesterols,LDLsarethe‘badcholesterols’àHighLDLinthebloodatrestandafterafastwouldbeindicativeofarelativelyhigherriskofanadversecardiovasculareventdownstreamàHDLaresaidtomovefattothegallbladderforexcretion,thesearethe‘goodcholesterols’Plasmacholesterolandheartdisease

• Cholesterolhasavitalroleinmanufacturingsomevitamins(vitaminD),somehormonesandcellmembranes.

• However,thebodymanufacturesallthecholesterolitneeds;additionalintakeinthedietwillpotentiallyleadtoaccumulationofcholesterolinthebody.Thatsaid,dietarycholesterolintakeisnotbelievedtoincreaseplasma[LDL]tothesameextentasdietaryintakeofsaturatedfat.

àWhilenotneededfromthediet(wecanproduceenoughforourselves)itisanimportantnutrient>hormones,cellmembranesetcàEggsareoneofthehighestsourcesofdietarycholesterol>somesayifyouhavehighbloodcholesterollevels,youshouldstopconsumingsomuch>thiswasthe‘80s>nowitisrealisedthatconsumingsaturatedfatisjustas,ifnotmoredangerous,fordrivinguptheLDLintheblood.TransfattyacidshaveanastyeffectonLDLconcentrationsintheblood

• Thereisarelationshipbetweenbloodcholesterolconcentrationsandatherosclerosis(CVD)thathasdrivenpublichealthpolicy–thatis,weshouldreduceourintakeofsaturatedfatinthediet.

àHaslongbeenthearelationshipbetween;Highsatfatintake<->highplasmaLDL<->CVD

• NootherbloodconstituentvariesacrosstheWorldasmuchascholesterol.InPNG,TC=2.6;inFinland,TC=7.0mmol.l-1.

• TotalcholesterolseemstobethestrongestdeterminantofCHDriskatapopulationlevel.(CoronaryHeartDisease)

• Itis‘dose-related’–thereisnodiscernible‘criticallevel’.• However,theratioofHDL:LDLismostinformativewithrespecttoCHDriskwithinahomogenous

population.àRelatingtothe3rdpoint;thereisnolevelthatonceyouhitityouareatgreaterriskofdiseaseàAnindividualmayhavehigherthanaverageofLDLconc.ThoughtheirratioofHDL:LDLmaybefine>thisseemstoberelatedtotheoverallhealthandrisk

StudyhereaboutcoronaryheartdiseaseandcaloriesoffatconsumedàThereisarelationshipbetweenprecentofcaloriesoffatinthedietandCHDper1000àSugar-refinedcarbohydratecanbeparticularlydamagingàAdvisingtokeeplevelsofsatfatandsugardowninthediet;thisisgenerallyinallprocessedfood,soitisgenerallyrecommendedtoavoidprocessedfoodsCholesterolàCHDisagreatcauseofmortality.Therelationshipbetweenallcausemortalityandplasmacholesterol

• Saturated fats (and trans fatty acids) consumed in the diet raise cholesterol levels in the blood - to a much greater extent than dietary cholesterol does.

• Saturated fats are not exclusively derived from animal products. (Palm and coconut oils)

• So,thereepidemiologicaldatahavelongrevealedarelationshipbetweenbloodcholesterolandmortality.

• Whatisthephysiologicalmechanism?

Low-densitylipoproteins(LDL’s)

• LDLmoleculesaretakenupintheendothelium,wheretheyareoxidized.Thisoxidationtriggersinfiltrationofothercellsanddebrisandatherosclerosisdevelops.

• Low-gradeinflammationandoxidativestressplayscentralroleintheseriesofeventsleadingtoLDLoxidationintheendothelium.

• HighcirculatingglucoseandLDLconcentrationscontributetotheincreasedinflammatoryresponseandgreateroxidativestress.

CouldantioxidantsupplementationreduceLDLoxidationandpreventorslowarthrosclerosis?

• Ameta-analysisbyVivekananthanetal(2003;TheLancet)showedthatthereisnobenefitofvitaminEsupplementationoncvdiseaserisk.Moreover,betacarotenesupplementationappearedtoincreaseall-causemortalityrisk.

• Amorerecentmeta-analysiswith22RCTconfirmedthatantioxidantsupplementationhasnoinfluenceonatheroscleroticevents(KatsikiandManes;2009;ClinicalNutrition).

àTherewasthethoughtoftakingantioxidantstopreventorslowatherosclerosisandheartdiseaseàTheoriginalstudieswerepromisinginrats,thoughtinhumans,itseemedtofail.Itdoesn’tseemtohaveanyeffectonthedevelopmentofatherosclerosisHigh-densitylipoproteins(HDLs)

• HDLremovescholesterolfromtheperipheriestotheliverfordisposal.ExercisecanincreaseHDL’sbuthaslittleinfluenceonLDL’s.

• [HDL]increaseswithexercise(8-10milesperweekrunning;Woodetal.,1994)àHdlconcentrationdoesn’tseemtobeinfluencedbydietàItseemsthatexerciseisthebestwaytopushupHDLconcentration

• KelleyandKelley(2009)havepublishedtheresultsofameta-analysis(n=29)examiningtheinfluenceofresistancetrainingonbloodlipids.

• Resistancetrainingcan:o Reduce[TC]by2.7%,reduce[LDL]by4.6%,reduce[TG]by6.4%andincrease[HDL]by1.4%.o Ofthe29studiesanalysed,thefrequencyofRTwaseither2or3xpw,therepswerebetween7-

30,exercisesrangedbetween3-16andthedurationofthetrainingperiodslasted8-78weeks.àDon’tneedtoknowthenumbers,justunderstandingtheconceptsandsupportthenotionthatresistancetrainingcanbegoodforhealth

GraphonriskofcardiovasculareventsandHDLcholesterollevels

àThelowertheHDLconcentrationinthebloodthehighertheriskàThisissimilartotheexercisegraphwherethoseintheextremecategoryofexercise,andthisgraphhere,haveagreaterrisk

• [HDL]shouldbe1.60mmol.l-1.A0.026mmol.l-1increasein[HDL]reducesCHDriskby2-3%.• Smokingdecreases[HDL].• HDLlevelsincreasewithoestrogenbutdietgenerallyhaslittleeffectonplasma[HDL].

àAsmallincreaseinHDLpromotesasignificantreductionoftheriskofCHD

AstudyonsmokinginEuropeanmen,Americanmen,andSouthernEuropeanmen(Mediterranean)

àTheNorthernEuropeanmen,andAmericanmenhaveamuchgreaterriskthanthoseontheMediterraneandietàThesteepnessrepresentstherateofdeathtodyingfromCHDàEventhoughthereishugeamountofsmokers,theMediterraneandiethasaprotectiveaffectàThefrequencyandmagnitudeofinsulinspikesinisthoughttoberelatedtovasculardysfunction

• ThereisaschoolofthoughtthatchallengesthecauseandeffectrelationshipbetweensaturatedfatintakeandCVD.

• Anumberofscientistsbelievethatitissugarinthedietthatistheprimarycauseofvasculardysfunction.

• Aswewilldiscussinthediabeteslecture,thereisaverycloserelationshipbetweendiabetesandCVD.• Thereasonisthatglucoseinthebloodisassociatedwithoxidativestress,insulinisrelatedtosub-

clinicalinflammationandcombined,theseresultinendothelialdysfunctionandmicro-damagethatincreasestherisksofCVD.

Thrombogenesis

• Plateletaggregationisdeterminedbyacomplexseriesoffactors.• Forexample,stearicacid(18:0)hasnoeffecton[LDL]butincreasesclotting.Oleicacid(18:1)isanti-

thrombogenic.àClottingintheblood>thrombogenesisàThebloodcanclottoomuch,aclotinabloodvesselcanlatertraveltothebrain(stroke)orheart,etc.

• Greenland’sIndigenouspeoplehavetraditionallyconsumedahighfat,highcholesteroldietyettheyhavelowCVD.

• Thereasonforthisparadoxisthattheyconsumehighlevelsofthepolyunsaturatedfattyacids,particularlythen-3fattyacidsEPA(C20:5)andDHA(22:6)fromcoldwaterfish.

• Highbloodlevelsoflong-chainn-3fattyacidsareassociatedwithalowerriskofsuddendeathamongmenwithoutevidenceofpriorCVD(Albertetal.,2002).

àomega6promoteclotting(wegenerallygetquitealotofthesethroughvegetables)àomega3balancethisastheyareanti-clottingàthereneedstobeabalancebetweenomega3and6fattyacids!!!!àthebenefitsofEPAandDHAseemtonotjustresidewithheartdiseasebutalsoawiderangeofhealthbenefits

• DespitestrongepidemiologicaldataandasoundbiologicalexplanationforareducedriskofCVDwithincreasedintakeoffishoil,interventionstudieshavefailedtoshowarelationship.However,thereisevidencethatitmayreducetheriskofCVeventswiththoseatparticularlyhighriskofCVD.

• WhiletrialsinvestigatingtherelationshipbetweenDHAandEPAintakeandmaintenanceofcognitivefunctionandpsychologicalhealthhavebeeinconsistent,thereisemergingevidencethattheymaybebeneficial.

àTheweightofevidenceisgrowing,thereseemstobesufficientevidencethatitplaysanimportantroleàHighfibredietsdon’thavethatgreatofaneffect

FibreintakeandreducedriskofCVD• Pectins(fruits)andsolublefibres(oatsandbarley)reducecholesterol,butnotbymuch.• Averyhighintakeofsolublefibreisnecessarytoelicitasmalleffecton[LDL].Insolublefibrehasno

effecton[LDL].• Theeffectiscertainlylessthanthatwhichoccursinresponsetochangingintakesofsaturatedfat.

àFibreisveryeffectiveofblunteningtheBlGluspike

• Mechanismsincludesterolexcretion;removalofbilesalts(whicharemadefromcholesterol).• Highfibredietsmakethepersonfeel‘fuller’andcaninturnreducesaturatedfatintake.• Fibreintakeshouldaverageatleast30-40gaday.• Giaccoetal.(2009)haverecentlyshownthatconsumptionof23.1g/dayofcerealfibrereduced[LDL]by

4.3%andTCby4.9%-injust3weeks.Alcohol

• Alcoholintakemobilizestriglycerides(TGs).• TheMediterraneandietthatisassociatedwitharelativelylowriskofCVDincludesredwine.Research

hasconsideredwhetherredwineconfersprotectionagainstCVD.The‘FrenchParadox’also.....• àTheFrenchsmokeanddrinkredwine,andtheirhealthisgenerallygood• Redwineprovidesachemicalcalledresveratrol(apolyphenol).Resveratrollevelsarehigherinred

winesproducedinharshclimates(fromredgrapesthathavehadastressedlife).àItisimportantnottooveremphasistheeffectofdrinkingredwineandresveratrol

• Berrouguietal.(2009;Atherosclerosis)haveattemptedtoelucidatethemechanismsthroughwhichresveratrolreducestheriskofCVD.

• In‘test-tube’studies,researchershaveshownthatresveratrolhasthepotentialtoreduceLDLoxidation.Whetherthistranslatesintomeaningfulbenefitsforhumansisnotclear,thoughevidencesuggeststhatitmayconferbenefits.

• SomestudieshaveshownthatitreducesLDL,improvesendothelialfunctionandimprovesventricularfunction.

àWineandbeerdrinkersseemtobedifferentpeopleàMustfactorinpeopleslifestyle,youcan’tcherrypicksomethingsfromadiettogetthebenefitàItiseverythingincombination

• NB:resveratrolisbelievedtobeanticarcinogenicandit’sinfluenceoncoloncancerriskisbeinginvestigated.

• Therelationshipbetweendrinkingwine(vsbeer)andtheriskofincurringdiseasessuchasCVDanddiabeteshasbeeninvestigatedbyBarefootetal.(2002).

• Winedrinkershavebeenfoundtohavemoreservingsoffruitandvegetableseachday,consumelesscholesterolandsaturatedfat,consumemorefibreandarelesslikelytosmokewhencomparedtobeerdrinkers.

• TheresearchfindingsrelatedtoaprotectiveeffectofalcoholonCVDaremixed(andtherearebiases

thatoftengounreported).• Cancercouncilsrecommendabstinencefromalcohol(asdothemajorityofdoctors)anditisimportant

thatthismessagedoesnotgetcloudedbytheinconsistentresearchfindingsrelatingprotectionfromCVDbyalcohol.

• Itisalsoworthnotingthatflavonoidsinteahavebeenassociatedwithareducedriskofheartdisease

(Geleijnseetal.,2002).• Teaintake(likeredwine)isassociatedwithahealthylifestyle(relativelyleanpeople,lowincidenceof

smoking,healthydiet).• FlavonoidsprotectagainstLDLoxidation,reduceplateletaggregrationandimprovevascularfunction.

Hypertension(HT)

• HypertensionisassociatedwithanincreasedriskofCVDandstroke.• ObesityandalcoholintakearesignificantlyrelatedtoHT.• Alcoholintakemayincreasesympatheticoutflow,thusincreasingperipheralresistance.

àAsweagethebloodvesselslosetheirelasticityandhardenàHearthastopumpharderagainstthisperipheralresistance

• WithregardtosaltandHT,themechanismislessclear.Saltintakeisdifficulttomeasureandisgenerallyhighinprocessedfoods.

• 80%ofthesaltconsumedis‘hidden’inprocessedfood.• Weconsume9-12g/day–thisneedstobe5-6g/day.

àDon’tneedtoknownumbersfortheexam

• Hypertensivesmayhaveadefectintheirkidneys’abilitytoclearsodiumandwater.• Sodiummaycausevascularreactivityandincreasevasoconstriction.Itmayalsoraiseresting

catecholaminelevelsandrenalsympatheticnerveactivity.• Abouta10mmHgfallinsystolicBPisthemosthypertensivescanexpectfromalowsodiumdiet.Also,

only20-40%ofhypertensivesrespondtoareductionindietarysodium.However,thiswillreducetheriskofstrokeandCHDinthepopulation.

àThisisn’tmuchanddoesn’thappentoeverybodyàWhilethisdoesn’tseemtobethatmuch,atapopulationlevelthisisactuallyveryeffective

• Fungetal.(2009)examinedtheinfluenceoftheMediterraneandietonriskofstroke.• 74886women(agedbetween38and63years)intheNurses’StudycohortwithoutahistoryofCVDand

diabeteswerefollowedbetween1984and2004.• RelativeriskofCVD,strokeandcombinedfatalcardiovasculardiseasewasassessed.

àpointoftheaboveisthat;noprocessedfood>lowerriskofdiseasesàThisiswhatwasthought10-15yearsago???

• ParticipantswerealsoassignedaMediterraneanDietScore(MDS)fromdietaryrecordscollectedsixtimesduringthe20-yearperiod.

• Accountingforconfoundingvariables,thoseinthetopquintileoftheMDShadthelowestriskofCVDmortalityandstroke.

Exerciseandhypertension

• Exercisetraining(includingenduranceandresistancetraining)forthosewithcontrolledhypertensioncanreduceSBPby~10mmHg.

• Themechanismsinclude:• Reducedsympatheticresponse–thatinturnreducesperipheralvasoconstriction.• Increasednitricoxide(NO)production–thatinturn,increasesperipheralvasodilation.

• Inadditiontoageneralimprovementinvascularfunction(peripherally),plasmareninlevelsmayalso

fallwithtrainingandthiswillimprovekidneyfunction.MetabolicRate

• Restingmetabolicrate(RMR)istheminimumamountofenergyrequiredforthemaintenanceofbodyfunctions.Itaccountsfor60-70%ofthetotaldailyenergyexpenditure.

• Thus,anyinterventionthatraisesRMRhasimportantimplicationsforweightcontrol.• Astrongrelationshipexistsbetweenleanbodymass(LBM)andrestingmetabolicrate(RMR);trained

individualsarecharacterizedbyhighRMR’s.(Thisiswhatwasthough10-15yearsago)

• ThishigherRMRintrainedindividualshasbeenattributedtoalterationsinthyroidfunction,increasesinlipolysis,proteinsynthesis,glycogensynthesisandhigherLBM.

• Thatsaid,thereislittleagreementintheresearchliteraturethatexercisetrainingcanincreaseRMR.àVeryfewpeoplehaveconsistentlyshownthatmusclecanincreaseRMR

• Leeetal.(2009;MSSE)recruited20healthymales,dividedthemintotwogroupsandtrainedoneofthegroupsfor12weeks.

• Theyjoggedat60-80%VO2maxfor25-40minutes,3-4xpw.• TherewasnoincreaseinRMRinthetraininggroupbutthecontrolgroupdecreasedtheirRMR.

• Theauthorsspeculatedthatthisdecreasewasseasonalandthattheexerciseinterventionmaintained

RMRwhichwouldhaveotherwisedecreasedintheexperimentalgroup.

• Jenningsetal.(2009;MSSE)examinedwhether6monthsofexercisetrainingwithpreviouslyinactivemen(aged>50years)whohadtypeIIdiabetescouldincreasetheirRMR.

• NeitherresistancetrainingnorendurancetrainingincreasedRMRdespiteincreasesinstrengthandVO2max.However,thereweretrends.

• Kirketal.(2009;MSSE)alsoexaminedwhether6monthsofresistancetrainingwithyoungadults(21years,BMI=27)couldincreaseRMR.

• RT=onesetofnineexercises(3-61RM),3xpw.Eachsessiontook11minutestocomplete.• Whole-roomindirectcalorimetryrevealedasignificantincreaseinRMR.

àExaminingallthestudiesontrainingandRMR,thereareinconsistencies

• Thompsonetal.(1996)foundthatRMRfallswithdietarymanipulationalone(5MJ/day,lowfat)andwithdietarymanipulationplusexercise.However,thefallindietalonewasgreaterthandietplusexercise.So,additionofexercisepreventstheextentofthefallinRMR.

AndroidvsGynoid

• ThetwoindividualsinthepreviouspictureshavethesameBMI.Android(apple)Pear(gynoid)

• However,themale(withtheandroidshape)hasamuchhigherriskofCVD,diabetesanddyslipidemia.

• Visceralfatishigher(e.g.intheliver,heart,pancreas).Thisleadstometabolicdysfunctionoftheseorgans.

• AndroidshapeshavelowerHDLconcentrationsandhighercirculatingtotaltriglycerides.

àThevisceralfatispackedaroundtheorgansandseemstobemorereadilyreleasedintothebloodstreamàThisiswhereproblemsarise(subcutaneousfatseemsalotlessharmful)

• Increasesinvisceralfatprecedethedevelopmentofinsulinresistance.• Itmaybethatdeepabdominal(visceral)fatisreleasedmoreeasilyintotheportalcirculation.• Visceralfatdoesappeartobemetabolicallydifferenttosub-cutaneousfat.• Exercisetrainingseemstoresultinpreferentiallossofvisceral(ratherthansubcutaneous)fat

• TheInternationalDiabetesFederationhasproposedthatformales,waistcircumferenceneedstobe

keptbelow94cm;forfemales,thecut-offis80cm(Albertietal.,2009;Circulation).• ThesewaistcircumferencesequatetoaBMIofaround25.• Waistcircumferencecut-offswilldifferwithethnicgroup.

àDon’tneedtoknownumbers

Metabolicsyndrome

• Themetabolicsyndromeisaclusterofthefollowingconditions:o Abdominalobesityo Impairedglucosecontrolo Hypertensiono Hyperlipidemia(hyperlipidemia>highbloodfatconcentration)

• Thecombinedeffectsoftheseconditionsisgreaterthanthesumoftheriskofeachindividualcondition

• 34%ofadultsindevelopedcountrieshavethemetabolicsyndrome.àInactivityanddietarethemaincontributorstothisTheMediterraneandiet

• In1980,KeysandcolleaguesconcludedthatfarmersonCreteconsumedveryhighamountsofdietaryfat,yethadthelowestlevelsofCVD.

• KeycomponentsoftheMediterraneandietinclude:o Fish(andverylittleredmeat)o Monounsaturatedfatsfromoliveoilo Fruitandvegetableso Wholegrains,legumesandnutso Moderatealcoholconsumption

àItistheinteractionbetweenallthesethings,youcan’ttakeonethingfromthisdiet,putitinapill.

• ItisnotclearwhetherthebenefitsoftheMediterraneandietareduetosomeoftheindividualcomponentsoracombinedeffect.

• Omega3polyunsaturatedfatsimprovebloodlipidprofiles,reduceinflammationandbloodcoagulation.• Unsaturatedfats(oliveoil)havephenolsthatareassociatedwithreducedinflammationandimproved

endothelialfunction.Bothleadtolowerbloodpressure.• Fruitandvegetableshaveawiderangeofphytochemicalsthatleadtolowerbloodpressure.• Wholegrainfoodhighinfibre,nutsandlegumesimprovethebloodlipidprofileandreducemarkersof

inflammation.àBloodvesselfunctionisvimportantinavoidingcardiacdiseaseInflammation

• Inflammationoccursinthebodyinresponsetoanydisturbanceinhomeostasis.Uncontrolled-excessiveinflammationcanresultintissueinjury–and,forexample,tothedevelopmentofatherosclerosis.

• Smoking,hypertension,highfatdiets,highglucoseconcentrationscauseendothelialcellstobindleukocytes–thatthensecretechemokinesthatattractmonocytestoentertheintimawheretheymatureintomacrophages.

àInflammationinthecontextofCVD,isconsideredlowgrade(notlikehightemperature),theseeffectthebloodvessels,occurringoveralifetimewithpoordiet,puttingthemthroughlowgradeinflammationeveryday

• Analternativeviewisthathighpost-prandialconcentrationsofglucoseandtriglyceridesgenerateexcessfreeradicalsandthesethentriggerinflammationandendothelialdysfunction.

• Eitherway,highcirculatingconcentrationsofglucoseand/orfatleadtolow-levelinflammationandanincreasedriskofatherosclerosis.

ThisoxidativestressinthebodyandthemarkersthatgowithitTheinflammatoryresponsecancausedamagetothebloodvesselsTheprincipleismostimportanthereProcessedfood>graphshowsthehighertheBlGluLevelsthegreatertheoxidativestressinthebody(triangle)CRP>creactiveproteinsystemicmarkerofinflammation(redbox)Nitrotyrosine>measureofoxidativestress(green)FMD>flowmediateddilation>howthebloodvesselbehave,youdontwantthistodecrease.Thissuggestsimpairmentpostmeal.Ifitisfailingtodilatesomethingiswrong>thisissuggestingthatthereisproblemsbeingcausedhere>eventhoughthisisinanextremecase>itgoestoshowthatthisaddsupoveralifetimeThisaffectlastsforatleast4hours

• Reducingtheintakeofprocessedfoodwillreducetheinflammatoryresponse.• However,exercisewillalsoreduceit–viatwomechanisms.• 1.Exerciselowerspostprandialglucoseconcentrations;asingle90inboutofmoderate-intensityexercise

within2hrbeforeorafteramealwillreducebloodglucoselevelsandtriglyceridelevelsbyupto50%.• 2.Contractingskeletalmuscleproducesandreleasesmyokines(knownalsoascytokines).

• Duringexercise,interluken-6(IL-6)isproducedbymuscles.• IL-6stimulatestheappearanceoftheanti-inflammatorycytokinessuchasIL-1raandIL-10andinhibits

theproductionofthepro-inflammatorycytokine:tumournecrosisfactor-alpha(TNF-).• TNF-hasbeenimplicatedinavarietyofdiseases,includingautoimmunediseases,insulinresistance,

andcancer.• Thus,IL-6producesananti-inflammatoryenvironmentasaresultofexercisethroughreducingTNF-

production.