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The Hangover: Pathophysiology and Treatment of an Alcohol-Induced Hangover

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FromTheArchives–TheHangover:
PathophysiologyandTreatmentofan
AlcoholInducedHangover
January16,2014
Pleaseenjoythispostfromthearchives,datedMay27,2011
ByAnthonyTolisano
FacultyPeerReviewed
Thesunlightforcesitswayintoyoureyes,stabbingatyourcortex.
Suddenly,awaveofnauseaanddiarrheagripsyourstomach,
threateningtoevacuateitscontents.Yourushtothebathroom,
trippingovertheclothesthatspeckleyourapartment.Yourheart
poundsinsideyourchestandyourhandsshakeeversosubtly.
Yourmindisinafogandthedetailsoflastnight’spartyareablur.
Soundfamiliar?
Ifyou’reanythinglikethemillionsofpeoplewhohaveeverdrunk
toomuchalcohol,you’llimmediatelyrecognizethesordidsignsofahangover.It’saconditionthat
iswellrecognizedyetpoorlyunderstood.Descriptionsaboundinpopcultureandliterature,
saturatingthepublicconsciousness.Yet,agreatdealofscientificresearchhashadonlylimited
successinexplainingitspathophysiology.
Thebasicconceptissimple.Ahangoverissecondarytobingedrinking,theconsumptionofan
excessiveamountofalcoholinarelativelyshorttimeperiod.TheNationalInstituteofAlcohol
AbuseandAlcoholismdefinesbingedrinkingasariseinbloodalcoholcontent(BAC)togreater
thanorequalto0.08%withintwohours,ormoresimply,theconsumptionofatleastfour(for
women)orfive(formen)alcoholicbeveragesinasingledrinkingsession.[1]Ofnote,mostpeople
whobingedrinkconsumefarmorethan45drinks,imbibinganaverageofeightpernight.[2]
Bingedrinkingisextremelycommon,especiallyamongyoungadults,andremainstheleading
causeofdeatheachyearamongcollegeagedstudentsintheUS,[3]withsimilarworldwiderates
ofproblematicalcoholuseacrossEurope,SouthAmerica,andAustralia.[4]Thedangersof
consumingtoomuchalcoholareobvious.Amongotherthings,motorvehicleaccidents,sexual
assaults,andviolencearemorecommonamongtheacutelyintoxicated.[5]Ahangover,however,
islargelyregardedasanannoyance.Itisdefinedasthatwhichoccursaftertheacuteintoxication
hassubsided,reachingitsgreatestintensityastheBACapproacheszero.Itlastsforupto24hours
andconsistsofamyriadofsignsandsymptoms,fromconstitutional(fatigueandmalaise)and
gastrointestinal(lossofappetite,diarrhea,andnausea),tonociceptive(headacheandmyalgias)and
autonomic(tachycardiaandtremor).Sleepdisturbances,includingincreasedslowwaveand
decreasedREMsleep,andneurocognitivesymptoms,suchasdecreasedattentionandmemory
problems,arealsocommon.[6]Furthermore,theimpairmentofone’spsychomotorperformance
canbesubstantial.Infact,ifyouthinksoberingupissufficientforsafelydrivinghome,youmay
bewrong.Studieshaveshownthatindividualswhosufferfromhangoversymptomshavea
decreasedabilitytooperateamotorvehicle.[7],[8]Combinedwiththelossofworkdaysand
decreasedproductivityfromhangovers,perhapsthisannoyingdayafteraffairisn’tsobenignafter
all.
Sowhatisthepathophysiologicalexplanationforahangover?Ifahangoverissecondarytothe
clearanceofethanolfromthebody(whenBACisequaltozero),isn’titthesamephenomenonas
acutealcoholwithdrawal?Theanswer,quitesimply,isno.Alcoholwithdrawalissecondarytothe
developmentofphysiologicalalcoholdependenceoverthecourseofmanydrinkingepisodes,
whereasthehangoveroccursafteronenightofdrinkinganddoesnotrequirealcoholdependence.
Anotherpossibilityisthatthatahangovermaybetheresultofthedirecteffectsoflastnight’s
extracurricularactivities.Thatis,ahangovermaybethelastingeffectsofelectrolyteimbalances,
hypoglycemia,anddehydration,whichpersistlongerthantheethanolitself.Unfortunately,studies
haveshownlittlecorrelationbetweenhangoversymptomsandserumelectrolytes,bloodglucose,
ormarkersofdehydrationsuchasantidiuretichormoneandrenin.Asimilarargumenthasbeen
madeforacetaldehyde,ametabolicbreakdownproductofethanolthathasvasodilatoryand
gastrointestinaleffectsonthebody.Again,limitedevidencehasbeenfoundlinkingacetaldehyde
levelswithhangoverseverity.[9]Perhapsunderstandingtheeffectofalcoholconsumptiononthe
immunesystemwillelucidatetheunderlyingcauseofthehangover.Anumberofstudieshave
shownthatfollowinganightofheavydrinkingthereisanupregulationofcytokinesand
prostaglandins.Specifically,increasedplasmalevelsofinterleukin10,interleukin12,and
interferongammaweremeasuredinindividualssufferingfromhangoversymptomslongaftertheir
lastdrink.ProstaglandinE2,thromboxaneB2,andCreactiveproteinweresimilarlyincreased.
Mostimportantly,theserumlevelsoftheseinflammatorymarkersweredirectlyrelatedtothe
degreeofhangoversymptoms.[10]Thisassociationhasbeensupportedbyevidencethattreatment
withcyclooxygenaseinhibitorsleadstoadecreaseintheseinflammatoryfactorsandasubsequent
decreaseinhangoversymptoms.[11]Unfortunately,thisfindinghasnotbeenregularlyrepeatedin
welldesignedstudies.
Whiletheexactbiologicalbasisofahangovermayremainsomewhatofamystery,thereisgood
evidencethatcertainfactorsexacerbatehangoversymptoms.Certainly,sleepdeprivationandthe
simultaneousconsumptionofotherpsychoactivesubstancesworsenhangoversymptoms.Perhaps
lessintuitively,sodoesthetypeofalcohol,eveniftwodrinkscontainthesamealcoholcontentby
volume.Simplyput,darkerliquorsgenerallycauseworsehangoversymptoms.Itisthoughtthat
thisisduetosocalledcongeners,byproductsofthefermentationprocessrelatedtothedifferent
casksandgrainsused.Forexample,ambercoloredbourbonhasacongenerlevelof37times
thatofvodka,causingworsehangoversymptomsthanitsclearercousin.[12]Attheendoftheday,
hangoversareunpleasant,tosaytheleast.WhileaGooglesearchforhangoverremediesreveals
thousandsofhitsforreportedly“clinicallyproven”cures,therearereallynogoodoptions.No
evidencesupportsBvitamins,tomatojuice,orfattyfoods.[13]Other,morecolorfuloptions,such
astheuseofartichokeextract,revealnodifferencebetweenthestudygroupandthecontrolgroup.
[14]Theonebrightspot?Pricklypear(Opuntiaficusindica)extracthasbeenshowntodecrease
theinflammationassociatedwithhangoversandthesubsequentincidenceofnausea,drymouth,
andanorexia.[15]Asyoumayhavesuspected,however,themostimportantfactorinpreventinga
hangoverremainsabstinenceormoderation.Inotherwords,avoidbingedrinkingentirely.
Alternatealcoholicandnonalcoholicbeveragesorspreadyouralcoholconsumptionoveralonger
periodoftime.
AnthonyTolisanoisa3rdyearmedicalstudentatNYULangoneMedicalCenter
PeerreviewedbyBarbaraPorter,sectioneditor,ClinicalCorrelations
ImagecourtesyofGoogleImages
References:
1.NationalInstituteofAlcoholAbuseandAlcoholism.NIAAAcouncilapprovesdefinitionof
bingedrinking.NIAAANewsletter2004;No.3,p.3.Available
athttp://pubs.niaaa.nih.gov//Newsletter/winter2004/Newsletter_Number3.htm#council.Accessed
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8.StephensR,LingJ,HeffernanTM,HeatherN,JonesK.Areviewoftheliteratureonthe
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subjects.Alcohol.2003;31(3):167170.
11..KaivolaS,ParantainenJ,OstermanT,TimonenH.Hangoverheadacheandprostaglandins:
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hangover,sleep,andnextdayneurocognitiveperformanceinyoungadults.AlcoholClinExpRes.
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assn.org/cgi/content/full/164/12/1334
ResearchGate has not been able to resolve any citations for this publication.
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The Pathology of Alcohol Hangover
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  • Jun 2010
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Alcohol hangover: A critical review of explanatory factors
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Alcohol has had a long and complicated role in human society and health. Excessive use of alcohol causes enormous morbidity and mortality worldwide, but the health effects of alcohol use within recommended guidelines are diverse and complex. Established effects include increased high-density lipoprotein cholesterol and antithrombotic activity, providing plausible mechanisms for the observed association of moderate drinking with lower risk of coronary heart disease but higher risk of hemorrhagic stroke. However, moderate drinking increases sex steroid hormone levels and may interfere with folate metabolism, both of which are potential mechanisms for the observed associations of moderate drinking with several forms of cancer, particularly breast and colorectal. Genetic susceptibility to the effects of alcohol on cancer and coronary heart disease also differs across the population. Recommendations regarding moderate drinking must be individualized to reflect the potentially competing effects of alcohol on several chronic diseases.
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Hangover Headache and Prostaglandins: Prophylactic Treatment with Tolfenamic Acid
Article
  • Apr 1983
Tolfenamic acid (TA), a potent inhibitor of prostaglandin (PG) biosynthesis and action, was tested prophylactically against hangover symptoms in 30 healthy volunteers in a double-blind cross-over study. One capsule of TA (200 mg) or placebo was taken before starting to drink alcohol and another before going to bed. The hangover symptoms were evaluated in the morning. TA was found significantly better than placebo in the subjective evaluation of drug efficacy (p less than 0.001) and in reducing the reported hangover symptoms in general (p less than 0.01). In the TA group, significantly lower symptom scores were obtained for headache (p less than 0.01), and for nausea, vomiting, irritation, tremor, thirst and dryness of mouth (all p less than 0.05). In a separate study with eight participants, plasma levels of PGs were followed during ingestion of alcohol with or without TA. The plasma concentrations of PGE2 and TXB2 (a metabolite of thromboxane A2) were lower in the TA group during alcohol ingestion, while PGF2 alpha and 6-keto-PGF1 alpha (a metabolite of prostacyclin) were unaffected. TXB2 correlated with blood alcohol levels in a U-shaped manner.
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Effectiveness of artichoke extract in preventing alcohol-induced hangovers: A randomized controlled trial
Article
  • Jan 2004
Extract of globe artichoke (Cynara scolymus) is promoted as a possible preventive or cure for alcohol-induced hangover symptoms. However, few rigorous clinical trials have assessed the effects of artichoke extract, and none has examined the effects in relation to hangovers. We undertook this study to test whether artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover. We recruited healthy adult volunteers between 18 and 65 years of age to participate in a randomized double-blind crossover trial. Participants received either 3 capsules of commercially available standardized artichoke extract or indistinguishable, inert placebo capsules immediately before and after alcohol exposure. After a 1-week washout period the volunteers received the opposite treatment. Participants predefined the type and amount of alcoholic beverage that would give them a hangover and ate the same meal before commencing alcohol consumption on the 2 study days. The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions. Secondary outcome measures were differences between the interventions in scores using a mood profile questionnaire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure. Fifteen volunteers participated in the study. The mean number (and standard deviation) of alcohol units (each unit being 7.9 g, or 10 mL, of ethanol) consumed during treatment with artichoke extract and placebo was 10.7 (3.1) and 10.5 (2.4) respectively, equivalent to 1.2 (0.3) and 1.2 (0.2) g of alcohol per kilogram body weight. The volume of nonalcoholic drink consumed and the duration of sleep were similar during the artichoke extract and placebo interventions. None of the outcome measures differed significantly between interventions. Adverse events were rare and were mild and transient. Our results suggest that artichoke extract is not effective in preventing the signs and symptoms of alcohol-induced hangover. Larger studies are required to confirm these findings.
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Effects of alcohol hangover on cytokine production in healthy subjects
Article
  • Dec 2003
  • ALCOHOL
A hangover is the syndrome of physical and mental symptoms that occurs 8 to 16 h after alcohol consumption with a zero level of alcohol. The aim of the current study was to investigate the effects of the alcohol hangover on cytokine production in healthy subjects. The hangover state was defined as 13 h after drinking 1.5 g/kg of alcohol (blood alcohol level=0). A venous blood sample was taken from 20 healthy adult men before consumption of alcohol and during the hangover state. Peripheral blood mononuclear cells were separated and stimulated with phytohemagglutinin. An enzyme-linked immunosorbent assay was used to measure the production of the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We found that the concentrations of IL-10, IL-12, and IFN-gamma were significantly increased during the hangover state compared with the concentrations in normal conditions. These results support the suggestion that the dysregulated cytokine pathway (IL-10, IL-12, and IFN-gamma) is associated with the symptoms of hangovers.
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Effect of Opuntia ficus indica on Symptoms of the Alcohol Hangover
Article
  • Jun 2004
  • ARCH INTERN MED
The severity of the alcohol hangover may be related to inflammation induced by impurities in the alcohol beverage and byproducts of alcohol metabolism. An extract of the Opuntia ficus indica (OFI) plant diminishes the inflammatory response to stressful stimuli. In this double-blind, placebo-controlled, crossover trial, 64 healthy, young adult volunteers were randomly assigned to receive OFI (1600 IU) and identical placebo, given 5 hours before alcohol consumption. During 4 hours, subjects consumed up to 1.75 g of alcohol per kilogram of body weight. Hangover severity (9 symptoms) and overall well-being were assessed on a scale (0-6), and blood and urine samples were obtained the following morning. Two weeks later, the study protocol was repeated with OFI and placebo reversed. Fifty-five subjects completed both the OFI and placebo arms of the study. Three of the 9 symptoms-nausea, dry mouth, and anorexia-were significantly reduced by OFI (all P<.05). Overall, the symptom index was reduced by 2.7 points on average (95% confidence interval, -0.2 to 5.5; P =.07), and the risk of a severe hangover (>/=18 points) was reduced by half (odds ratio, 0.38; 95% confidence interval, 0.16-0.88; P =.02). C-reactive protein levels were strongly associated with hangover severity; the mean symptom index was 4.1 (95% confidence interval, 1.2-7.1; P =.007) higher in subjects with morning C-reactive protein levels greater than 1.0 mg/L. In addition, C-reactive protein levels were 40% higher after subjects consumed placebo compared with OFI. The symptoms of the alcohol hangover are largely due to the activation of inflammation. An extract of the OFI plant has a moderate effect on reducing hangover symptoms, apparently by inhibiting the production of inflammatory mediators.
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College Students’ Alcohol Use: A Critical Review
Article
  • Feb 2005
This integrative review of college students' alcohol use covers research papers as well as review and theoretical papers published between 1990 and 2004. To conduct this review, abstracts were identified by searching Medline (PubMed), Ingenta, ERIC, PsycInfo, and Health Reference Center Academic using the following words: alcohol and college drinking, binge drinking, college students and undergraduates and the years 1990 to 2004. From an initial list of over 400 abstracts, 203 papers were identified and considered for this review. A developmental perspective of college drinking was assumed, and the chapter is organized within five domains: biology, identity, cognition, affiliation, and achievement. In addition, research pertaining to the harmful consequences of college drinking and the assessment of risky drinking is reviewed and discussed. The chapter concludes with the identification of gaps in knowledge and implications for future research.
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