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niaaa Spectrum Volume 2, Issue 3 | September 2010 | http://www.spectrum.niaaa.nih.gov Many people who develop alcohol dependence do so fairly soon after their first drink: 50% in less than 5 years 24% in less than 2 years 14% in less than 1 year U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • National Institutes of Health • National Institute on Alcohol Abuse and Alcoholism FEATURE YOU ARE WHAT YOU EAT AND DRINK: NEW RESEARCH FOCUSES ON ALCOHOL AND NUTRITION More and more researchers are investigating how alcohol and nutrition interact to impact our biology, our behavior, and our health. In addition to dependence, alcohol can trigger a host of health problems, including certain cancers, cardiovascular disease, liver These images compare the synapse formation (appears in red) in the neurons from two mouse fetuses. The one on the left is from the fetus that had sufficient DHA during gestation while the one on the right is from the fetus that did not. The neurons derived from the DHA-deficient mouse fetus show 50 percent fewer synapses. The inhibited synapse formation due to DHA-deficiency may have significant implication in developing depression and alcohol dependence. Photo courtesy of Dr. Hee-Yong Kim, NIAAA intramural program of (Journal of Neurochemistry. 2009 Oct;111(2):510-21). disease, and fetal alcohol syndrome. Researchers are interested in what role nutrition can play in preventing and treating these alcohol-related health outcomes. “When you think about alcohol as part of your overall diet—a food like any other that you consume with other foods, it leads to lots of questions—like does alcohol consumption change food intake, does food intake change alcohol intake, and how do various patterns of alcohol and food consumption together influence the risk of chronic disease?” said Dr. Rosalind Breslow, an epidemiologist in NIAAA’s Division of Epidemiology and Prevention Research. Dr. Breslow recently collaborated with researchers at the National Cancer Institute (NCI) and the U.S. Department of Agriculture (USDA) to investigate some of the connections between alcohol and diet. She led a team that analyzed data collected from participants in the National Health and Nutrition Examination Survey (NHANES) and from scores on the Healthy Eating Index-2005 (HEI). NHANES is a survey of nationally representative samples of the U.S. population that the U.S. Department of Health and Human Services’ Centers for Disease Control and Prevention conducts on an ongoing basis. The USDA created HEI to measure how healthy our diets are based on how closely they conform to the 2005 U.S. dietary guidelines for Americans. IN THIS ISSUE FEATURES 1 You Are What You Eat and Drink: New Research Focuses on Alcohol and Nutrition 2 Alcohol’s Health Effects Go Beyond Hangovers CHARTICLE 3 How Long Does It Take Alcohol Dependence To Develop? PHOTO ESSAY 4 In the Line of Duty: How the Liver Becomes Damaged as It Degrades Alcohol NEWS FROM THE FIELD 5 Moderate Drinkers May Live Longer Than Non- Drinkers 5 More Adults Drinking… and in Ways That Increase Risk 6 New Compound Improves Obesity-Related Health Complications 7 Half-hour Interventions Can Help Reduce Peer Violence and Alcohol Consequences Among Teens 5 QUESTIONS WITH... 7 Sam Zakhari, Ph.D.
Transcript
Page 1: NIAAA Spectrum, Vol. 2, Issue 3, September 2010 · drinking can lead to accidents and dependence, and even liver disease. But that’s only part of the story. Unlike other drugs,

niaaa SpectrumVolume 2, Issue 3 | September 2010 | http://www.spectrum.niaaa.nih.gov

Many people who develop alcohol dependence

do so fairly soon after their first drink:

50% in less than 5 years

24% in lessthan 2 years

14% in lessthan

1 year

U.S.DEPARTMENTOFHEALTHANDHUMANSERVICES•NationalInstitutesofHealth•NationalInstituteonAlcoholAbuseandAlcoholism

FEATURE

YOUAREWHATYOUEATANDDRINK:NEWRESEARCHFOCUSESONALCOHOLANDNUTRITIONMoreandmoreresearchersareinvestigatinghowalcoholandnutritioninteracttoimpactourbiology,ourbehavior,andourhealth.Inadditiontodependence,alcoholcantriggerahostofhealthproblems,includingcertaincancers,cardiovasculardisease,liver

These images compare the synapse formation (appears in red) in the neurons from two mouse fetuses. The one on the left is from the fetus that had sufficient DHA during gestation while the one on the right is from the fetus that did not. The neurons derived from the DHA-deficient mouse fetus show 50 percent fewer synapses. The inhibited synapse formation due to DHA-deficiency may have significant implication in developing depression and alcohol dependence.

Photo courtesy of Dr. Hee-Yong Kim, NIAAA intramural program of (Journal of Neurochemistry. 2009 Oct;111(2):510-21).

disease,andfetalalcoholsyndrome.Researchersareinterestedinwhatrolenutritioncanplayinpreventingandtreatingthesealcohol-relatedhealthoutcomes.

“Whenyouthinkaboutalcoholaspartofyouroveralldiet—afoodlikeanyotherthatyouconsumewithotherfoods,itleadstolotsofquestions—likedoesalcoholconsumptionchangefoodintake,doesfoodintakechangealcohol

intake,andhowdovariouspatternsofalcoholandfoodconsumptiontogetherinfluencetheriskofchronicdisease?”saidDr.RosalindBreslow,anepidemiologistinNIAAA’sDivisionofEpidemiologyandPreventionResearch.

Dr.BreslowrecentlycollaboratedwithresearchersattheNationalCancerInstitute(NCI)andtheU.S.DepartmentofAgriculture(USDA)toinvestigatesomeoftheconnectionsbetweenalcoholanddiet.SheledateamthatanalyzeddatacollectedfromparticipantsintheNationalHealthandNutritionExaminationSurvey(NHANES)andfromscoresontheHealthyEating

Index-2005(HEI).NHANESisasurveyofnationallyrepresentativesamplesoftheU.S.populationthattheU.S.DepartmentofHealthandHumanServices’CentersforDiseaseControlandPreventionconductsonanongoingbasis.TheUSDAcreatedHEItomeasurehowhealthyourdietsarebasedonhowcloselytheyconformtothe2005U.S.dietaryguidelinesforAmericans.

INTHISISSUEFEATURES

1YouAreWhatYouEatandDrink:NewResearchFocusesonAlcohol andNutrition

2Alcohol’sHealthEffectsGoBeyondHangovers

CHARTICLE3HowLongDoesItTakeAlcoholDependenceToDevelop?

PHOTOESSAY4IntheLineofDuty:HowtheLiverBecomesDamagedasItDegradesAlcohol

NEWSFROMTHEFIELD5ModerateDrinkersMayLiveLongerThanNon-Drinkers

5MoreAdultsDrinking…andinWaysThatIncreaseRisk

6NewCompoundImprovesObesity-RelatedHealthComplications

7Half-hourInterventionsCanHelpReducePeerViolenceandAlcoholConsequencesAmongTeens

5QUESTIONSWITH...7SamZakhari,Ph.D.

Page 2: NIAAA Spectrum, Vol. 2, Issue 3, September 2010 · drinking can lead to accidents and dependence, and even liver disease. But that’s only part of the story. Unlike other drugs,

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Dr.Breslowandherteamfoundthatheavierdrinkerstendtoeatlessfruitandconsumemorecaloriesfromacombinationofalcoholicbeveragesandfoodshighinunhealthyfatsandaddedsugars.Meninparticularwhoconsumedalotofcaloriesfromalcoholalsoatelesswholegrains,animportantsourceofdietaryfiber,andlesslow-fatdairyproducts,includingmilk,yogurt,cheese,andsoybeverages,importantsourcesofcalciumandothernutrients.WomenwhodranktoomuchalsohadlowerHEI-2005scores.

Overall,theresearchersfoundthatasastudyparticipant’saveragedailynumberofdrinkswentup,theirHEI-2005scorewentdown.Thismaybeonereasonwhyheavydrinkersaremoresusceptibletoalcohol’snegativehealtheffects,includingcertaincancers,livercirrhosis,andheartdisease.

Peoplewhodrinkmorealsoconsumelessomega-3fattyacids,whicharefatsthathelpcomposeourbrainandarecriticalforbrainfunction.Thesefatsarefoundinfishlikesalmon,sardines,andtuna.What’smore,alcoholactivelydepletesomega-3sfromthebrain.

“Wecanonlygetomega-3fattyacidsthroughourdiets.Alcoholicshaveverylittleomega-3sgoinginandalotofthemgoingout,”saidJosephHibbeln,M.D.,apsychiatristandactingchief,SectiononNutritionalNeurosciences

atNIAAAandcaptain,U.S.PublicHealthService.

Alcoholcandepleteoneparticulartypeofomega-3fattyacidinthebrain,docosahexaenoicacid,orDHA,byhalf.

Dr.Hibbeln’sresearchismovingtowardunderstandingtheconsequencesofthisDHAdeficiencyforeveryone,includingalcoholics.Forexample,lowDHAlevelscanresultindepression,aggression,andimpulsivity.AsHibbelnstated,“Mymorethan20yearsofresearchindicatesthatpeoplewhoeatlittlefishareatmuchgreaterriskofdepression.”

AlackofDHAinthebraincanalsorundowndopaminelevels.“Itiswellknownthatchronicaddictedstatesarecharacterizedbydopaminedepletion,”explainedHibbeln.Dietsdeficientinomega-3scanlowerdopaminelevelsbyhalf.Arecentstudyintroducedmicewithadietlowinomega-3stolowlevelsofamphetamines.Themicereleaseddopamineatlevelssimilartoachronicallyaddictedanimal.Hibbelnattributesthisdopaminedeficiencytotheir“baddiet.”

Insufficientomega-3scanalsolinkdirectlytoacycleofaddiction.Toolittleomega-3s,coupledwithtoomanyomega-6fattyacids,whicharefatsinabundanceinthetypicalAmericandiet,canleadtoexcessfoodintake,excess

alcoholintake,andaninabilitytofeelsatiated.Thisimbalanceincreasesthecravingforalcohol,andcausesthosewhoaresusceptibletodrinktoomuch.

Onerecentstudyillustratesthepotentialforpositivelyimpactingalcoholdependencebyincreasingomega-3sinthediet.

Dr.Hibbelnoffered2gramsofomega-3sto96alcoholicsinearlyrecovery.Heverifiedthatparticipantsweretakingtheomega-3sbymeasuringthelevelsoffattyacidsintheirspinalfluid.Overthe90daysofthestudy,alcoholicswhotookomega-3shadanaverageofabout3.2drinkingdayscomparedtothe17.5drinkingdaysintheplacebogroup.

“Thisstudyof96alcoholicsprovidespromisingpilotdataforpotentialbenefitsofensuringadequatebrainnutritionamongalcoholicsinrecovery,”Hibbelnsaid.

Hibbelnplanstofocusfuturestudiesonevaluatingwhethertheseresultscanbereplicated.

Hibbeln’sandBreslow’sworkarejusttwoexamplesoftheresearchinvestigatingtheconnectionsbetweenalcoholandnutrition.

AsBreslowsaid,“It’saveryexcitingarea,withimplicationsforbothpublichealthandbasicresearch.”

Continued from page 1

FEATURE

ALCOHOL’SHEALTHEFFECTSGOBEYONDHANGOVERSAlcoholispartofourculture—weuseittocelebrateandsocialize,anditispartofmanyofourreligiousceremonies.

Butdrinkingtoomuch—onasingleoccasionorovertime—canhaveseriousconsequencesforourhealth.Theseconsequencesgofarbeyondhavingaheadacheandahangoverthat

makeusuncomfortable,butgoawayrelativelyquickly.

Mostpeoplerecognizethatexcessivedrinkingcanleadtoaccidentsanddependence,andevenliverdisease.Butthat’sonlypartofthestory.Unlikeotherdrugs,alcoholdispersesinallbodytissuesandthereforehasthepotentialtoharmmanyorgansystems.

Alcoholabusecandamageorgans,weakentheimmunesystem,andcontributetocancers.

Plus,muchlikesmoking,alcoholaffectsdifferentpeopledifferently.Genes,environment,andevendietcanplayaroleinwhetheryoudevelopanalcohol-relateddisease.

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Continued from page 2

Ontheflipside,somepeoplemayactuallybenefitfromdrinkingalcoholinsmallquantities.

Alcohol’seffectonyourheartisthebestexampleofalcohol’sdualeffects.

Drinkingalotoveralongtimeortoomuchonasingleoccasioncancauseheartproblemsincludinghighbloodpressure,strokes,arrhythmia,andcardiomyopathy,aconditionthatcausesyourheartmuscletoweakenanddroop.Butresearchalsoshowsthat

healthypeoplewhodrinkmoderateamountsofalcoholmayhavealowerriskofdevelopingcoronaryartery

diseasethanpeoplewhoneverdrinkatall.

Whiledrinkinginmoderationmaynotaffectthehealthofyourliver,heavydrinkingcandefinitelytakeitstoll.Yourliverhelpsridyourbodyofsubstancesthatcanbedangerous—includingalcohol.Bybreakingdownalcohol,yourliverproducestoxicbyproductsthatdamagelivercells,promoteinflammation,andweakenthebody’snaturaldefenses.Thiscanmakeconditionsripefordisorderslikesteatosis,fibrosis,andcirrhosis,anddangerousinflammationslikehepatitistodevelop.

Pancreaticinflammationscanalsodevelopinresponsetodrinkingtoomuch.Alcoholcausesthepancreastoproducetoxicsubstancesthatcaneventuallycauseinflammationandswellingintissuesinbloodvessels.Thisinflammation,calledpancreatitis,preventsthepancreasfromdigestingfoodandconvertingitintofueltopoweryourbody.

Asidefromdamagingyourorgans,drinkingtoomuchalcoholcanalsoincreaseyourriskofdevelopingcertaincancers,includingthoseofthemouth,esophagus,pharynx,larynx,liver, andbreast.

Alcoholalsocanweakenyourimmunesystem,makingyourbodyamucheasiertargetfordisease.Drinkingalotonasingleoccasionslowsyourbody’sabilitytowardoffinfections—evenupto24hoursaftergettingdrunk.Chronicdrinkersaremorelikelytocontractdiseaseslikepneumoniaandtuberculosisthanpeoplewhodonotdrinktoomuch.

Tolearnmoreaboutthehealtheffectsofalcohol,pleasedownloadNIAAA’snewestpublication,Beyond Hangovers: Understanding Alcohol’s Impact on Your Health. http://pubs.niaaa.nih.gov/publications/Hangovers/beyondHangovers.htm

CHARTICLE

HOWLONGDOESITTAKEALCOHOLDEPENDENCETODEVELOP?About1in7adultswhohavehadalcoholdependence,commonlyknownasalcoholism,developeditlessthanayearafterhavingtheirfirstdrink,accordingtoanationwidesurveyofU.S.adultsaged18orolder.1Aboutaquarterofpeoplewhohavehadalcoholdependencedevelopeditlessthan2yearsaftertheirfirstdrink,aboutathirdinlessthan3years,andabouthalfinlessthan5years.1

IntheUnitedStates,mostpeoplehavehadtheirfirstdrinkbythetimetheyleavehighschool.2Thisfact,combinedwiththerelativelyrapidonsetofdependenceinmanydrinkers,helpstoexplainwhyalcoholdependenceisfoundmostcommonlyinyoungadults.About1in9peopleaged18–24havealcoholdependence,morethantwicetheproportionofanyotheragegroup.3

Many people who develop alcohol dependence

do so fairly soon after their first drink:

50% in less than 5 years

24% in lessthan 2 years

14% in lessthan

1 year

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Thesurveyalsoshowsthatalcoholdependenceoccursonlyrarelyamongdrinkerswhoalwaysstaywithintheselimits:formen,nomorethan4drinksonanysingledayand14perweek;forwomen,nomorethan3drinksonanydayand7perweek.4

(1)UnpublisheddatafromtheNationalEpidemiologicSurveyonAlcoholandRelatedConditions(NESARC).

(2)FadenVF.TrendsininitiationofalcoholuseintheUnitedStates1975-2003.Alcoholism: Clinical and Experimental Research.2006June;30(6):1011-22.

(3)UnpublisheddatafromtheNESARC.

(4)DawsonDA,etal.Quantifyingtherisksassociatedwithexceedingrecommendeddrinkinglimits.Alcoholism: Clinical and Experimental Research.2005May;29(5):902-8.

Continued from page 2

INTHELINEOFDUTY:HOWTHELIVERBECOMESDAMAGEDASITDEGRADESALCOHOL

Thereprobablyisn’tamorevital—yetunderappreciated—organinthehumanbodythantheliver.Whilewemayrecognize,inthemostgeneralterms,therolethattheliverplays,manyofusdon’tfullyunderstanditsmanyfunctionsorvulnerabilities,particularlywithregardtoalcohol.Andyetthealcohol-liverconnectioniscritical,asmorethan2millionAmericanssufferfromliverdiseasecausedbyalcohol.

Byperformingmorethan500differentfunctions,theliverisessentialtoourhealth.Itsprimaryroleistofilterallthebloodinourbodiesbybreakingdownandeliminatingtoxinsandstoringexcessbloodsugar.Italsoproducesenzymesthatbreakdownfats,manufacturesproteinsthatregulatebloodclotting,andstoresanumberofessentialvitaminsandminerals.Alltold,theliverkeepsusalivebyenablingustodigestfood,absorbnutrients,controlinfections,andgetridoftoxicsubstancesinourbodies.

Whileliverproblemscanbeinherited,ordevelopedinresponsetocertainvirusesorchemicals,excessivealcoholuseplaysamajorrole.Tothehumanbody,alcoholisatoxinthatisbrokendownby

theliverasthebodybeginstheprocessofgettingridoftheseforeigncomponents.However,chronicheavydrinkingcausesthelivertobecomefatty.Thisconditionmakesthelivermorevulnerabletodangerousinflammation,suchasalcoholichepatitis,anditsassociatedcomplications.Withcontinueddrinking,persistentinflammationcausesthelivertobefibrotic,whichpreventsthenecessarybloodsupplyfromreachingthelivercells.Withouttheoxygenandothernutrientssuppliedbythisblood,thelivercellseventuallydieandarereplacedwithscartissue,creatingaconditionknownascirrhosis.Inmildcases,thelivercanactuallymakerepairsandcontinuetofunction.However,advancedcirrhosiscausescontinueddeteriorationandliverfailure.

Insomecases,lifestylechangescanhelptreatalcohol-liverproblems.Abstinencefromalcohol,alongwithbetternutritionandquittingsmoking,canhelppreventfurtherinjuryandkeepliverdiseasesincheck.Inextremecases,however,alivertransplantmaybetheprimarytreatmentoption.

PHOTOESSAY

Insert shows a portion of a liver scarred by cirrhosis, in comparison with a healthy liver.

Formoreinformationabouttheeffectsofalcoholontheliverandotherorgans,pleaseseethenewNIAAAbooklet,Beyond Hangovers: Understanding Alcohol’s Impact on Your Health. http://pubs.niaaa.nih.gov/publications/Hangovers/beyondHangovers.htm

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NEWSFROMTHEFIELD

MODERATEDRINKERSMAYLIVELONGERTHANNON-DRINKERS

When compared to abstainers or heavy drinkers, moderate drinkers have the lowest mortality risk.

AnewstudypublishedonlineinAlcoholism: Clinical and Experimental Researchhasshownthatmoderatedrinkingamongolderadultsis

associatedwithlowermortalityratesthanthoseobservedinadultswhodidnotdrinkatall.Whatmakesthisstudydifferentfrompreviousstudieswithsimilarfindingswasthatthe

researcherscontrolledforadditionalfactors,mostnotablynon-drinkerswhopreviouslydrankproblematically.Insimilarstudiesthatdonotcontrolforthehealthproblemscausedbypreviousheavydrinking,theinterpretationoffindingsregardingthepotentialbenefitofmoderatedrinkingismoredifficult.

Thestudy,ledbyCharlesJ.Holahan,Ph.D.,oftheUniversityofTexasatAustin,included1,824adultsbetweentheagesof55and65,andcontrolledforformerproblemdrinkingstatus,existinghealthproblems,andimportantsociodemographicandsocial-behavioralfactors.Whencontrolledforthesefactors,thedatashowedthatnon-drinkershada45percentincreasedmortalityriskovermoderatedrinkers.Additionally,heavy

drinkersshoweda51percentgreatermortalityriskthanmoderatedrinkers.

Theauthorsnotethat,“Theapparenthealth-protectiveeffectsofmoderatealcoholconsumptioncomparedtoabstentionmayberelatedtoreductionsincardiovascularillness.”Theauthorscaution,however,thatthesehealth-protectiveeffects“appeartobelimitedtoregularmoderatedrinking.Heavyepisodicdrinking—evenwhenaverageconsumptionremainsmoderate—isassociatedwithincreasedcardiovascularrisk.”Thearticleabstractcanbefoundhere:

Late-Life Alcohol Consumption and 20-Year Mortality. http://www.ncbi.nlm.nih.gov/pubmed/20735372

NEWSFROMTHEFIELD MOREADULTSDRINKING…ANDINWAYSTHATINCREASERISK

Studies reveal a significant increase in the proportion of men and women who drink.

ArecentanalysisofchangesfromtheNIAAA’s1992NationalLongitudinalAlcoholEpidemiologicSurvey(NLAES)tothe2002NationalEpidemiologicSurveyofAlcoholandRelatedConditions(NESARC)showsthatalargerproportionofU.S.adultsofallethnicities(White,Black,andHispanic)andbothsexeswerecurrentdrinkersin2002,withlittlechangeintheaveragenumberofdrinkspermonth.Notingincreasesinadultmaleswhodrinkfiveormoredrinksadayatleastonceamonth(Whites,Blacks,andHispanics)ordrinktointoxication(WhitesandBlacks),thestudysuggestsa“liberalization”ofattitudes

towardalcoholanddrinkingpracticeslinkedtoriskforalcoholusedisorderandotherconsequences.

Inadditiontoexaminingthe1992to2002trends,RaulCaetanoandco-authorsattheUniversityofTexasSchoolofPublicHealthandtheUniversityofNorthTexasHealthScienceCenteralsolookedatsociodemographicfactorsthatmightinfluencethem.TheiranalysiswaspostedonlineinthejournalAlcoholism: Clinical and Experimental ResearchandwillappearinitsOctober2010issue.

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NEWSFROMTHEFIELD:More Adults Drinking. . . Continued from page 5

Amongthefindings:

Adultmenwhowerecurrentdrinkersincreasedfromabout 53percentin1992to59percent(64percentofWhitemen, 60percentofHispanicmen,and53percentofBlackmen)in2002.

About36percentofadultwomen(47percentofWhitewomen,32percentofHispanicwomen,and30percentofBlackwomen)werecurrentdrinkersin2002,anincreasefrom28percentin1992.

Twoindicatorsofat-riskdrinkingroseamongmenwhoreportedthosepatternsatleastonceamonth:

drinkingfiveormoredrinks/dayincreasedamongWhite,Black,andHispanicmen,anddrinkingtointoxicationincreasedamongWhiteandBlackmen.

•Asinearlierstudies,malegender,singlestatusorlivingalone,U.S.birth,lowereducationallevel,andunemploymentwereassociatedwithhigherdrinkinglevels.

Althoughthestudycontrolledforage,maritalstatus,education,andincome,unknownsociodemographicfactorsmayhavecontributedtotheresults.“Understandingthecomplexreasonsforethnicandgenderdifferenceswill

requirecontinuousmonitoringandfurtheranalyses,”saysDr.Caetano.“Suchmonitoringisessentialfortargetedpreventionandmeaningfulpublicpolicy.”

Thearticleabstractcanbefoundhere:

Sociodemographic Predictors of Pattern and Volume of Alcohol Consumption Across Hispanics, Blacks, and Whites: 10-Year Trend (1992–2002). http://www.ncbi.nlm.nih.gov/pubmed/20645935

NEWCOMPOUNDIMPROVESOBESITY-RELATEDHEALTHCOMPLICATIONSNEWSFROMTHEFIELD

A compound developed by a trans-NIH team and others may block endocannabinoid activity without causing mental health problems.

resultfromblockingendocannabinoidreceptorsinthebrain.Theydevelopedsuchacompound,testeditinobesemice,andfoundthatsuchmiceshowedimprovementsinglucoseregulation,fattyliver,andplasmalipidprofiles.Theyalsofoundthatthecompounddidnotaffectbehavioralresponsesthataremediatedbyendocannabinoidreceptorsinthebrain.

“Thesepreliminaryfindingsareveryencouragingandwarrantfurthertestingofthiscompoundasapotentialpharmacotherapyforthemetabolicsyndromeassociatedwithobesity,”saidDr.Tam.

Thearticleabstractcanbefoundhere:

Peripheral CB1 Cannabinoid Receptor Blockade Improves Cardiometabolic Risk in Mouse Models of Obesity. http://www.ncbi.nlm.nih.gov/pubmed/20664173 Freefulltextofthearticleisavailableat: http://www.jci.org/articles/view/42551

Anexperimentalcompoundappearstoimprovemetabolicabnormalitiesassociatedwithobesity,accordingtoa

preliminarystudyledbyresearchersatNIAAA.AreportofthestudyappearedintheAugust2010issueoftheJournal of Clinical Investigation.

Previousstudieshaveshownthat

compoundsthatblocktheactivityofendocannabinoids—chemicalmessengersinthebodythathelpregulatemanybiologicalfunctions—canleadtoweightlossandimprovemetaboliccomplicationsofobesitysuchasdiabetesandinsulinresistance,changesinbloodlipidcomposition,andfattyliver.However,theclinicaladvancementofsuchcompoundshasbeenstymiedbybehavioralsideeffectsassociatedwiththeiruse,suchasanxiety,depression,andsuicidalthoughts.

GeorgeKunos,M.D.,Ph.D.,NIAAAscientificdirectorandthestudy’sseniorauthor,andfirstauthorJosephTam,D.D.S.,Ph.D.,oftheNIAAALaboratoryofPhysiologicStudies,collaboratedwithateamofscientistswithinandoutsideNIHtoinvestigateacompounddesignedtoavoidthosesideeffectswhilepreservingthebeneficialeffectsofblockingendocannabinoidactivity.

Dr.Kunosexplainedthatendocannabinoidreceptorsarepresentinthebrainaswellasinperipheraltissues,includingtheliver,skeletalmuscles,pancreas,andfattytissues.Activationofperipheralendocannabinoidreceptorscontributestoobesity-relatedmetabolicandhormonalabnormalities.

Theresearchersreasonedthatacompoundthatisunabletogetintothebrainwouldselectivelyblocktheactivityofendocannabinoidreceptorsinperipheraltissues,andthereforemightalleviatemetabolicandhormonalproblemsrelatedtoobesitywhileavoidingthebehavioralproblemsthat

5QUESTIONSWITH...

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NEWSFROMTHEFIELD HALF-HOURINTERVENTIONSCANHELPREDUCEPEERVIOLENCEANDALCOHOLCONSEQUENCESAMONGTEENS

Six months after receiving a brief intervention in the emergency department, participants maintain reduction in alcohol consequences.

ResearchersaffiliatedwiththeUniversityofMichiganhavefoundthatabriefinterventioninanemergencydepartment(ED)settingcanhelpreducepeerviolenceandtheconsequencesofalcoholuseinadolescents.Theresearchersscreenedpatientsbetweenages14and18todeterminetheiruseofalcoholandexperiencewithpeeraggressionbothasperpetratorandvictim.Thosewhohadexperienced

5QUESTIONSWITH...

1. Ingeneral,doyoubelievethatAmericanstrulyappreciateallofthewaysthatalcoholcanimpacttheirhealth?

Generally,no.Weseemtounderstand,atleastin

generalterms,thedangersofdrinkinganddriving,andtheeffectsofchronicdrinkingontheliverandtheriskofdependence.Butthoseareonlypartofthefullpicture;ourresearchshowsthatalcohol’seffectsarewideranging,affectingeveryorganfromthebrain(cognitiveandbehavioraldeficits)

totheheart(cardiomyopathyandhypertension),andfrompancreatitistosuppressionoftheimmunesystem,andeventocancerrisk.Forexample,itmightsurprisepeopletoknowthatpeoplewhodrinkheavilyonholidaysdevelopwhatiscalled“holidayheartsyndrome”wheretheheartbeatsirregularly(knownasarrhythmias)—thisconditioncanbefatal.Drinkingtoomuchonanemptystomachafterfastingchangesthechemistryoftheblood,causingwhatiscalledlactacidosisandketoacidosis(especiallyindiabetics)andcanearnyouatriptotheemergencyroom.

Inaddition,it’simportanttoknowthatalcoholaffectsdifferentpeopledifferently,dependingongenes,environment,andevendiet.Forexample,halfofthepopulationofAsiandescenthasadefectiveenzymethatmetabolizesacetaldehyde,thefirstproductofalcoholbreakdown,leadingtotheaccumulationofacetaldehyde,whichcausesthemtoflush,havenauseaandfastheartrate,sweat,andsimplyfeelmiserable.Thisisnotabadthingbecause,inmostcases,thisisaprotectivemechanismfromdevelopingalcoholism.

SAMZAKHARI,PH.D.Dr. Zakhari is the director of the NIAAA Division of Metabolism and Health Effects

bothaggressionandalcoholusewererandomizedtoreceivea35-minuteinterventiondeliveredeitherbyacomputeroratherapist.Acontrolgroupreceivedabrochure.Thebriefinterventionincludedreviewofgoals,tailoredfeedback,decisionalbalanceexercise,roleplays,andreferrals.TheirfindingswerepublishedintheAugust4,2010,issueoftheJournal of the American Medical Association.

Theresearchersfollowedupwithparticipants3monthsand6monthslater.Atthe3-monthfollowup,theyfoundthatparticipantswhoreceivedthebriefinterventionfromatherapistwerelesslikelytoreportseverepeeraggression,experienceofpeerviolence,andviolenceconsequenceswhencomparedwiththecontrolgroup.Atthe6-monthfollowup,thoseinboththetherapistandcomputerinterventiongroupsshowedreductionsinalcohol

consequencescomparedwiththoseinthecontrolgroup.

ManyadolescentsseekcareintheED,particularlyun-orunder-insuredindividualsandthosewhobelievetheyaretoooldforpediatriccarebutwhohavenotsoughtoutregularadultmedicalcare.Becauseviolenceisaleadingcauseofmorbidityandmortalityinthisagegroup,theauthorsbelievethat,“adolescentsseekingcareintheEDareanimportantpopulationforinjurypreventionbasedonincreasedriskofproblemsrelatedtoalcoholandviolence.”

Thearticleabstractcanbefoundhere:

Effects of a Brief Intervention for Reducing Violence and Alcohol Misuse Among Adolescents: A Randomized Controlled Trial. http://www.ncbi.nlm.nih.gov/pubmed/20682932

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Volume2, Issue3 | September2010

Alcoholcanevendamageinnocentfetuses,whodonotdrinkvoluntarily.Whenapregnantmotherdrinks,alcoholcouldcausemorphological,structural,andfunctionaldamagetothebrainandotherorgansoftheunborn.Themostseverecaseiscalledfetalalcoholsyndrome,wherethechildhassmallphysicalandbrainsizeandamultitudeofcognitiveandbehavioraldeficitsthatmayputhimorherinconflictwiththelaw.

Overall,Ithinkweknowquitealotaboutalcoholandhealth,butweneedtogobeyondthecurrentunderstandingsowecanmakeinformeddecisionsaboutourdrinking.

2.Whataresomethingsweneedtoconsideraboutalcoholasweage?

That’sanimportantquestion,becausedifferentalcoholissuesseemtotakeprecedenceatdifferentstagesacrossthelifespan.Foryouthandyoungadults,theconsequencesofbingedrinkingareprominent.Itisnottrueatallthattheyoungareinvincibletoalcohol’seffects—justlookatthealmost2,000liveslostannuallyoncollegecampusesacrosstheNationduetounbridleddrinking.Thosewhoareluckyenoughnottosuccumbmaycausedamagetotheirendocrinesystem,resultinginirregularorabsentmenstrualcycleinwomenandadecreaseinspermcountinmen.It’salsothetimethatmanypeoplebegintodevelopdependence;thosewhostartdrinkingattheyoungageof18toearlytwentieshaveahighriskofdevelopingalcoholdependence.

Asweage,otherissuesbegintoemerge.Forexample,afteralong,harddayofwork,peopletendtodrinktounwindandrelaxandtorelievestress.Interestingly,alcohol’sphysiologicaleffectsonthestressaxis(hypothalamic-pituitary-adrenalaxis)mimicstress.So,notonlydoesalcoholnotrelievestress,butconsumedinhighamounts,alcoholcanrobthebodyofimportantvitaminsandmineralsthatareessentialforenzymaticactivities.Inaddition,peoplewhotendtotreatahangoverwithacetaminophencancauseirreparabledamagetotheirliver.

Seniorsnotonlymetabolizealcoholataslowerratethanyoungadultsbutinvariablyaremorelikelytotakeoneormoremedicationsthatinteractwithalcohol.Excessivealcoholconsumptionmayincreasethetoxicityofsomemedications(e.g.,antihistamines,antidepressants,anxiolytics)ordecreasetheefficacyofothers(e.g.,antidiabetics,antihypertensives).Furthermore,drinkingtoomuchcanimpairgaitandmayresultinfallsandbreakingofbrittlebones.

3.We’relearningmoreaboutgenderdifferencesaswell.Arethere

anyspecificissuesthatwomenshouldconsider?

Yes.Ingeneral,womenaremoresusceptibletoalcohol-inducedtissuedamagethanmen.Imaginea120-poundwomansittingnexttoa350-poundlinebackeratabar,andbothhaveadrink.Thealcohollevelinherbloodwillbehigherbecauseofhersizeandlowerwatercontentofherbody.Asaresult,womenaremoresusceptibletoalcohol-induceddamagetothebrain,heart,andliver.Moderatedrinking,therefore,isdefinedasnomorethanonedrinkadayforawomanandnomorethantwodrinksadayforaman.

Inaddition,womenwhoarepregnantortryingtoconceiveshouldabstainfromdrinkingsincethatcouldharmthefetus.Itcouldresultinfetalalcoholsyndromeoramilderformofbehavioralandcognitivedysfunction.Alcoholalso

increasestheriskofbreastcancer,especiallyinsusceptiblewomen.

4. Therehasalwaysbeenmuchdebateaboutthepotentialhealthbenefitsofmoderatedrinking.Canyoushedanylightonthisissue?

Numerousepidemiologicalstudieshaveshownthatmoderatedrinkingdecreasestheriskofcoronaryarterydiseaseandischemicstroke,protectsagainstcongestiveheartfailureandtype-2diabetes,reducesmortalityaftermyocardialinfarction,andenhancescognition.However,theseeffectsaremanifestedonanindividualbasis,andnoteveryonemayhavethesamebenefits.Iwouldurgeindividualstoconsultwiththeirphysicianbeforedrinking,sincepeoplewithafamilyhistoryofalcoholismmaybeathigherriskfordevelopingalcoholism.

5. Yourbackgroundisinpharmacology.Ifyouweren’tinthisresearchfield,whatothercareerpathmightyouhavechosen?

WhenIwasinhighschoolmypassionwasinmathandphysics.However,duetocircumstancesoutofmycontrol,Iendedupinthemedicalfield.Thatwasgreatbecauseithelpedmedealwithvariousmedicalsituationsinthefamily,andheightenedmyawarenessofhealthyfood.Iverymuchenjoygourmetcookingand,afterretirement,Iamlookingforwardtousingthistalenttohavefamilyandfriendsenjoymoderatedrinkingwithspecialmeals!

ABOUT USNIAAA SpectrumisNIAAA’sfirst-everwebzine.Withengagingfeaturearticles,shortnewsupdates,andcolorfulgraphics,NIAAA SpectrumoffersaccessibleandrelevantinformationonNIAAAandthealcoholresearchfieldforawiderangeofaudiences.Eachissueincludesfeature-lengthstories,newsupdatesfromthefield,charticlesandphotoessays,andaninterviewwithanNIAAAstaffmemberoralcoholresearcher.NIAAA Spectrum ispublishedthreetimesayear.

CONTACT USNational Institute on Alcohol Abuse and Alcoholism (NIAAA)5635FishersLane,MSC9304Bethesda,MD20892-9304Communications/PublicInfo:301–443–3860 http://www.spectrum.niaaa.nih.gov


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