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C l i n i c a l S t u d y

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I N D I A N J O U R N A L O F C L I N I C A L P R A C T I C E Vol. 15, No. 11

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Evaluation of the Efficacy and Safety of“PartySmart” in the Prevention of Alcohol-inducedHangover: A Prospective, Randomized, DoubleBlind, Comparative, Phase III Clinical Trial

Shalini*Ramakrishna**

MB Manu†

SA Kolhapure‡

Clinical

S t u d y

Alcohol-induced hangover is a poorly understoodphysiological manifestation of the biochemical effects

of alcoholic beverages on the body.

*Professor of Medicine,Sri Siddartha Medical College,Tumkur, India.**Executive, Biochemistry,†Executive, Clinical Pharmacology,‡Senior Medical Advisor,R&D Center,The Himalaya Drug Company,Bangalore, India.Address for correspondence:Dr SA Kolhapure,Senior Medical Advisor,R&D Center,The Himalaya Drug Company,Bangalore - 562 123, India.E-mail: [email protected]

AbstractAbstractAbstractAbstractAbstract“Alcohol-induced hangover”,

is a poorly understoodphysiological manifestation ofthe biochemical effects of alcoholon the body. There are variousformulations, which are beingpromoted as a cure foralcohol-induced hangover; butthese formulations have not beenevaluated for their efficacy and

safety, in controlled clinical trials.This study was planned to evaluatethe comparative efficacy and safetyof “PartySmart” in theprevention of thea l c o h o l - i n d u c e dhangover symptoms,with one of theformulations, which isbeing promoted as acure for alcohol-induced hangover.

The present studywas a prospective,randomized, doubleblind, comparative,phase III clinical trial.

A total of 10 healthy maleparticipants, who were occasionalsocial alcohol drinkers, and who

AbbreviationsADH : Alcohol dehydrogenaseALDH : Aldehyde dehydrogenaseBAC : Blood alcohol concentrationBMI : Body mass indexCRF : Case record formHCl : Hydrochloric acidHS : Highly significantNAD : Nicotinamide adenine dinucleotideNS : Not significantPOMS : Profile of mood states

questionnaire questionnaireS : Significant


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were willing to give informedconsent were included in the study.The “PartySmart” group receiveda capsule of “PartySmart” beforealcohol consumption, and thevolunteers from the compared druggroup consumed the other drug asper the recommended dose. Allthe volunteers were assessed atbaseline and at 2 and 10 hoursafter receiving the study drugs forphysical changes, and blood andurinary alcohol and acetaldehydelevels. All the participants hadtheir food from the same restaurant,where they had same type of food,on the study day after consumingalcohol. All the participantsconsumed same brand and type ofalcohol; and the details of numberof alcoholic drinks consumed byeach volunteer, the time of ‘goingto bed’ and ‘rising in the morning’were recorded in a structured caserecord form (CRF). The profileof mood states questionnaire(POMS questionnaire), predefinedsymptom score scale, and visualanalog score scale were used toassess the intensity of hangover,and the final hangover scores werederived after averaging thesescores. The predefined primaryeff icacy endpoints were thedifference in the final hangoverscores, physical parameters, andblood and urinary alcohol andacetaldehyde levels. Thepredefined secondary safetyendpoints were reduced incidenceof adverse effects and overallcompliance to the drugs underinvestigation. All the adverseevents reported by the subjects orobserved by the investigators wererecorded with information about

the severity, date of onset, durationand action taken regarding thestudy drugs. The data analysis wasperformed according to intent-to-treat principles.

This study observed asignificant difference in the meanfinal hangover score, which wassignif icantly lower in the“PartySmart” group than in thecompared drug group. There was asignificant difference in the meanblood alcohol levels after 10 hours,a highly significant difference inthe mean blood acetaldehydelevels after 2 hours and a significantdifference after 10 hours, in boththe groups. There was a significantdifference in the mean urinaryalcohol levels after 2 and 10 hours,in both the groups. There was alsoa significant difference in the meanurinary acetaldehyde levels after2 and 10 hours, in both the groups.There were no clinically significantadverse reactions, in both thegroups and the overall compliancewas good. These results suggestthat “PartySmart” prevents thebinding of acetaldehyde to cellproteins, causing a higher initialblood level and a subsequent rapidelimination, and the subsequentlower levels of alcohol andacetaldehyde in the bloodreflected in the decreased finalhangover score. Therefore, it maybe concluded that “PartySmart” iseffective and safe for usage in theprevention of alcohol-inducedhangover, as compared to the otherformulation.

IntroductionIntroductionIntroductionIntroductionIntroductionHangover, over?

Doesn’t matter hard or soft,

They will both leave you lost!

You could be coming,going or staying;

You’ll never know, just keepon praying.

All those brain cells had to die,the question is,

Was it worth the high1?

Alcohol-induced hangover,also referred as “veisalgia” (fromthe Norwegian kveis for “uneasinessfollowing debauchery” and Greek“algia” for “pain”), is a poorlyunderstood physiologicalmanifestation of the biochemicaleffects of alcoholic beverages onthe body. Researchers suspectthat both the breakdown productsof alcohol metabolism (esp.acetylaldehyde), and otherchemicals commonly found inalcoholic beverages ( i .e. ,congeners) are in part responsiblefor the hangover. Secondary causesinclude the altered sleep patternsinduced by drinking, and otherrecreational drugs used inconjunction with alcohol. Whilethe causes of the hangover mayvary from person to person,hangovers can occur in light,moderate and heavy drinkers,and have major repercussionsnot only for individuals, butalso for the society at large.Alcohol hangover is commonlycharacterized by headache,nausea, polyuria, polydipsia,and fatigue2.

There are various formulations,which are being promoted as acure for alcohol-induced hangover,but these formulations have notbeen evaluated for the efficacyand safety, in controlled clinicaltrials, however, neither the changesin various biochemical parameters


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and cognitive impairments ontreatment with these drugs havebeen monitored.

“PartySmart” is a polyherbalformulation containing the extractsof Phoenix dactylifera, Cichoriumintybus, Andrographis paniculata,Vitis vinifera, Phyllanthus amarusand Emblica officinalis. Somestudies have shown that“PartySmart” is useful inpreventing alcohol-inducedhangover; and previous studieshave demonstrated that pre-treatment with “PartySmart” beforealcohol ingestion was associatedwith rapid elimination of alcoholand acetaldehyde3-5.

This study was planned toevaluate the comparative efficacyand safety of “PartySmart” in theprevention of the alcohol-inducedhangover, with one of theformulations, which is promotedas a cure for alcohol-inducedhangover. This formulation withwhich the activity of “PartySmart”was compared is recommended ina serving size of one capsule, andeach capsule contains Thiamin(3 mg), Riboflavin (3.4 mg), Niacin(940 mg), Vitamin B6 (4 mg),Pantothenic acid (20 mg) andOpuntia ficus indica fruit extract(800 IU). The recommended doseis one-capsule/130 lbs. of bodyweight, with water, at least 2 hoursbefore consuming alcohol.

Aim of the studyAim of the studyAim of the studyAim of the studyAim of the studyThis study was planned to

evaluate the effect of “PartySmart”on blood and urinary levels ofalcohol and acetaldehyde, afteralcohol ingestion, and to assessthe comparative efficacy and safetyof “PartySmart” over the compared

drug in the prevention ofthe alcohol-induced hangoversymptoms.

Study designStudy designStudy designStudy designStudy designThe present study was a

prospective, randomized, doubleblind, comparative, phase IIIclinical trial. The duration of thestudy was 12 hours on a night, andthe ‘Institutional Ethics Committee’approved the study.

Materials andMaterials andMaterials andMaterials andMaterials andmethodsmethodsmethodsmethodsmethods

Inclusion criteriaInclusion criteriaInclusion criteriaInclusion criteriaInclusion criteriaA total of 10 healthy male

participants (from the pool ofvolunteers of the R&D Center,The Himalaya Drug Company,Bangalore, India), who wereoccasional social alcoholdrinkers, aged between25-45 years, in the body weightrange of 50-70 kg, and werewilling to give informed consentwere included in the study.

Exclusion criteriaExclusion criteriaExclusion criteriaExclusion criteriaExclusion criteriaExclusion cri teria were

volunteers with acid pepticdisorder, diabetes melli tus,neurological and psychiatricdisorders, chronic alcoholism,history of drug abuse, history ofalcohol abuse, and a score of morethan 2 points on the validated briefMichigan Alcoholism ScreeningTest (MAST)6. Similarly, volunteersconsuming certain concomitantmedications l ike antibiotics(furazolidone, griseofulvin,imidazoles), anticoagulants(warfarin), antidepressants( tr icyclic antidepressants) ,antihistamines, anticonvulsants(phenytoin), cardiovascular

medications (nitroglycerin,reserpine, methyldopa,hydralazine and guanethidine),sedatives and hypnotics(benzodiazepines), and thosevolunteers, who had knownhypersensitivity to alcohol andwere unwilling to give informedconsent were excluded from thestudy.

Randomization andRandomization andRandomization andRandomization andRandomization andblindingblindingblindingblindingblinding

A person unconnected with thestudy did the randomization inblocks of 4, by using a computergenerated random numberallocation. Double blinding wasdone, and neither the volunteers,nor the investigators were awareof the block size, and thereforewere unable to predict thetreatment allocation. The codeswere kept in sealed envelopesat a secure location to ensure thedouble blinding of the treatmentallocation.

Study drugsStudy drugsStudy drugsStudy drugsStudy drugsRandomly allocated volunteers

were divided into 2 groups:“PartySmart” group and the“Compared drug group”. The“PartySmart” group received onecapsule of “PartySmart” beforealcohol consumption (Batch No.41/2/R&D/HDC/2004) (Daily doseof a capsule of “PartySmart” hasbeen shown to be safe andeffective, therefore was consideredadequate for this study). Thecompared drug group was giventhe other formulation. Thevolunteers from the compared druggroup consumed the otherformulation as per therecommended dose.


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Study procedureStudy procedureStudy procedureStudy procedureStudy procedureAll the volunteers were

instructed to refrain fromconsuming any alcoholic beverageat least 48 hours before the study.To induce hangover symptoms, butprevent excessive drinking, all thevolunteers were asked to quantifytheir usual alcohol consumptionthat will reliably result in hangoversymptoms the next day, based ontheir previous personal experience.

All the volunteers wereassessed at baseline (before takingthe study drugs) and at 2 and 10hours after receiving the studydrugs for the physical changes,and for blood and urinary alcoholand acetaldehyde levels. Thealcohol and acetaldehyde levelswere measured by gaschromatography (Michro-9100,NETEL Chromatograph), which isa reliable and sensitive method forestimating blood and urinary levelsof alcohol and acetaldehyde. Allthe investigations were performedat the R&D Center, The HimalayaDrug Company, Bangalore, India.

The investigators supervisedthe intake of the “PartySmart”capsules and the other comparedformulation (caplets) by thevolunteers. All the participants hadtheir food from the same restaurant,where they had the same type offood, on the study day afterconsuming alcohol. To preventexcessive drinking, all theparticipants were reminded to limittheir alcohol consumption to thepredefined quantity. All theparticipants consumed same brandand type of alcohol (48w/v, 75%proof whisky), and the details ofnumber of alcoholic drinks

consumed by each volunteer, thetime of ‘going to bed’ and ‘risingin the morning’ were recordedin a structured CRF. Localaccommodation and taxi transportwere provided to all theparticipants.

Various studies have beenconducted on psychoactive drugsand also on alcohol-inducedhangover by using the POMS7.POMS questionnaire is a self-administered questionnaire and theobjective of POMS is to measurethe effects on mood of varioustherapeutic approaches. Onelimitation of the POMSquestionnaire is that the completePOMS has 65 different questions,perhaps a few too many to evaluateand therefore an abbreviatedversion, which included 12questions was used for this study.The volunteers were asked these12 questions in the local language(Kannada) by the investigators thenext morning, after the blood waswithdrawn (before breakfast). Thevolunteers were asked to tick-markon a paper, on which checkingboxes of 10 cm length were drawn,which was calibrated every 2 cm.One end of the row was marked asone and the other end was markedas 5. The volunteer’s were asked totick-mark on that predefined scalein the particular box, rating eachquestion in the following manner:1 = strongly disagree; 2 = disagree;3 = neutral; 4 = agree; 5 = stronglyagree.

The POMS questionnaire,which was used to evaluate thealcohol-induced hangover state inthis study included the following12 questions to evaluate the

concerned parameter, which wereas follows: (a) “Tension” - Do youfeel emotionally stretched out oras being under some kind ofunusual nervous strain or pressure?(b) “Anxiety” - Do you have afeeling of being generalized andvague, uneasy or apprehensive?(c) “Depression” - Do you have afeeling of sadness or helplessness?(d) “Dejection” - Are you feelingsomewhat hopeless with lowspirits? (e) “Anger” - Do you havea feeling of generalizeddispleasure or irritation or hostilityabout things happening aroundyou? (f) “Hostility” - Do you havea feeling of non-specif ic orgeneralized aggressiveness?(g) “Activity” - Are you feelingenergetic and lively enough, asyou feel usually? (h) “Vigor” - Doyou have enough strength of thebody and mind for your routineactivities? (i) “Fatigue” - Do youfeel physically and mentally tireddue to exertion? (j) “Inertia” - Doyou feel like lacking enoughinclination and willingness, foryour routine daily activities?(k) “Confusion” - Do you feelstrange or impaired regarding time,place or people around you?(i) “Bewilderment” - Are you feelingtoo disturbed due to inability tounderstand or comprehend thesequestions8?

Each volunteer also indicatedthe severity of each symptomexperienced during the alcohol-induced hangover, on a predefinedsymptom score scale, and anothervisual analog score scale9. Thephysical parameters for theevaluation of hangover included(1) headache, (2) facial and dermal


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flushing, (3) nausea, (4) burningsensation in the stomach,(5) tachycardia, (6) body ache,(7) burning sensation in the eyes,(8) drowsiness and (9) overallfeelings (euphoric/dysphoric andfresh/lousy). The volunteers wereasked to tick-mark on thesepredefined score scales their ratingof each symptom in the followingmanner: 1 = nil; 2 = negligible;3 = mild; 4 = moderate; 5 = severe.The final hangover scores wasderived after averaging the scoresof POMS, symptom score scale,and visual analog score scale.

Primary and secondaryPrimary and secondaryPrimary and secondaryPrimary and secondaryPrimary and secondaryendpointsendpointsendpointsendpointsendpoints

The predefined primaryendpoints were the difference inhangover scores, physicalparameters and blood and urinaryalcohol and acetaldehyde levels.The primary outcome measureswere assessed at baseline and after2 and 10 hours after alcoholexposure, on the next day. Thepredefined secondary endpointswere reduced incidence of adverseeffects and overall complianceto the formulations underinvestigation.

Intercurrent illness andIntercurrent illness andIntercurrent illness andIntercurrent illness andIntercurrent illness andconcomitant medicationconcomitant medicationconcomitant medicationconcomitant medicationconcomitant medication

The investigators recorded anyinformation about intercurrentillness, therapeutic interventionsand concomitant medication.Antacid or any other drug given forsymptomatic relief from acutealcohol-induced gastritis wasallowed concomitantly with thestudy medication.

Adverse eventsAdverse eventsAdverse eventsAdverse eventsAdverse eventsAll the adverse events reported

by the subjects or observed by theinvestigators were recorded withinformation about severity, date ofonset, duration and action takenregarding study drugs. Relation ofadverse events to study medicationwas predefined as “Unrelated”,“Possible”, and “Probable”.

Analysis of dataAnalysis of dataAnalysis of dataAnalysis of dataAnalysis of dataThe data analysis was

performed according to intent-to-treat principles. The “IndependentSample’s Unpaired ‘t’ Test” wasused to compare both the groupsfor baseline parameters, predefinedamount of alcohol to inducehangover, actual alcoholconsumption and changes invarious biochemical parameters.A two-sided “p” value of <0.05was considered significant, and apower of 80% was considered forthis trial.

ResultsResultsResultsResultsResultsThere were 5 volunteers in

each group (“PartySmart group”and “the “compared drug” group”).There was no significant differencein the age and body mass index(BMI) of the volunteers in both thegroups (t = 1.146, R2 = 0.1411,p = 0.2848; NS) (Table 1 andFig. 1). Similarly, there was nosignificant different in the meanpredefined amount of alcoholconsumption to experience thehangover (t = 0.00, R2 = 0.00, p =1; NS) (Table 1 and Fig. 2), andalso in the mean amount of alcoholactually consumed by thevolunteers ( t = 0.6325, R2 =0.04762, p = 0.5447; NS) (Table 1)from the both groups.

There was a signif icantdifference in the mean final

hangover score, which wassignif icantly higher in thecompared drug group, as comparedto the PartySmart group (t = 3.578,R2 = 0.6154, p = 0.0072; S) (Table1 and Fig. 3).

There was no significantdifference in both the groups, inthe mean blood alcohol levels after2 hours (t = 0.9253, R2 = 0.09668,p = 0.3819; NS) (Table 1 andFig. 4); but there was a significantdifference in the mean bloodalcohol levels after 10 hours (t =4.817, R2 = 0.7436, p = 0.0013; S)(Table 1 and Fig. 5). There was ahighly significant difference inboth the groups, in the mean bloodacetaldehyde levels after 2 hours(t = 5.754, R2 = 0.8054, p = 0.0004;HS) (Table 1 and Fig. 6) and asignificant difference after 10 hours(t = 3.679, R2 = 0.6285, p = 0.0062;S) (Table 1 and Fig. 7).

There was a signif icantdifference in both the groups,in the mean urinary alcohol levelsafter 2 hours (t = 2.425, R2 = 0.4236,p = 0.0415; S) (Table 1 and Fig. 8)and 10 hours (t = 4.463,R2 = 0.7134, p = 0.0021; S)(Table 1 and Fig. 9). There was asignificant difference in both thegroups, in the mean urinaryacetaldehyde levels after 2 hours(t = 3.034, R2 = 0.535, p = 0.0162;S) (Table 1 and Fig. 10) andafter 10 hours ( t = 4.337,R2 = 0.7016, p = 0.0025) (Table 1and Fig. 11).

There were no clinicallysignificant adverse reactions,either observed by the investigatorsor reported by the volunteers, inthe both groups and the overallcompliance was good.


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DiscussionDiscussionDiscussionDiscussionDiscussionAlcohols are organic

compounds consisting of a carbonskeleton with a hydroxyl group,and ethanol (grain alcohol),methanol (wood alcohol), andisopropanol (rubbing alcohol) arecommon examples. Ethanol isproduced by yeast maintained inanaerobic conditions by“fermentation”, and the reactionis catalyzed by the yeast enzymezymase, which is analogous to thehuman production of lactic acid(C

6H

12O

6→2CH

3CH

2OH + 2CO

2)10.

Researchers estimate that 20%of alcohol ingested passes through

the stomach to the blood, and thisabsorption is relatively slow and isalso unique in that few substancesare absorbed in the stomach. Theremaining 80% of alcohol ingestedis absorbed quickly into the bloodfrom the small intestine, and thepresence of food in the stomachincreases the t ime it takesfor alcohol to be absorbed intothe blood10.

Between 2% (at low BAC) and10% (at high BAC) of ethanol isexcreted directly through the lungs,urine or sweat, but the greater partis metabolized to acetaldehyde inthe liver. At least 2 metabolic

routes (each with dif ferentoptimal concentrations of ethanol),result in the metabolism ofapproximately one drink per hour.The most important pathway occursin the cell cytosol where alcoholdehydrogenase (ADH) producesacetaldehyde, which is thenrapidly destroyed by aldehydedehydrogenase (ALDH) in thecytosol and mitochondria. Each ofthese steps requires nicotinamideadenine dinucleotide (NAD) as acofactor, and it is the increasedratio of the reduced cofactor(NADH) to NAD (NADH:NAD) thatis responsible for many of the

Table 1

Analysis of various parameters of “PartySmart” and“Compared drug” groupsPartySmart Compared drug

Parameters group group Unpaired ‘t’ test summary

BMI 24.06 ± 0.63 26.24 ± 1.79 t = 1.146, R2 = 0.1411,p = 0.2848; NS

Predefined amount of 198.00 ± 7.34 198.00 ± 12.00 t = 0.00, R2 = 0.00, p = 1; NSalcohol (ml) consumed

Amount of alcohol 186.00 ± 11.22 198.00 ± 15.30 t = 0.6325, R2 = 0.04762,consumed (ml) p = 0.5447; NS

Severity of mean hangover 0.80 ± 0.20 2.40 ± 0.40 t = 3.578, R2 = 0.6154,p = 0.0072; S

Blood alcohol levels (mg/dl) 35.08 ± 4.86 29.32 ± 3.88 t = 0.9253, R2 = 0.09668,after 2 hours p = 0.3819; NS

Blood alcohol levels (mg/dl) 1.14 ± 0.63 7.68 ± 2.97 t = 4.817, R2 = 0.7436,after 10 hours p = 0.0013; S

Blood acetaldehyde levels 214.90 ± 23.81 74.34 ± 5.44 t = 5.754, R2 = 0.8054,(µg/dl) after 2 hours p = 0.0004; HS

Blood acetaldehyde levels 10.30 ± 1.59 37.69 ± 7.27 t = 3.679, R2 = 0.6285,(µg/dl) after 10 hours p = 0.0062; S

Urine alcohol levels (mg/dl) 17.42 ± 1.39 35.49 ± 7.32 t = 2.425, R2 = 0.4236,after 2 hours p = 0.0415; S

Urine alcohol levels (mg/dl) 8.59 ± 0.99 34.80 ± 5.79 t = 4.463, R2 = 0.7134,after 10 hours p = 0.0021; S

Urine acetaldehyde levels 37.68 ± 6.35 17.05 ± 2.43 t = 3.034, R2 = 0.535,(µg/ml) after 2 hours p = 0.0162; S

Urine acetaldehyde levels 59.78 ± 4.58 27.61 ± 5.84 t = 4.337, R2 = 0.7016,(µg/ml) after 10 hours p = 0.0025; S


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metabolic derangements observedafter drinking. A second pathwayoccurs in the microsomes of thesmooth endoplasmic reticulum (themicrosomal ethanol-oxidizingsystem, or MEOS), which isresponsible for 10% of ethanoloxidation at high blood alcoholconcentrations. Acetate combineswith a proton to form acetic acid,which can be further broken downto carbon dioxide and water orused to form fatty acids in theliver10.

Ethanol is a weakly chargedmolecule that moves easily throughcell membranes, rapidlyequilibrating between blood andtissues. The effects of drinkingdepend in part on the amount ofethanol consumed per unit of bodyweight. A level of 0.02-0.03 resultsfrom the ingestion of one to twotypical drinks10.

Ethanol is a central nervoussystem (CNS) depressant thatdecreases the activity of neurons,although some behavioralstimulation is observed at low blood

alcohol concentration (BAC).Ethanol has cross-tolerance,and shares a similar patternof behavioral problems withother brain depressants(benzodiazepines andbarbiturates). The intoxicatingeffects of alcohol appear to bedue to its actions at specificneurotransmitter receptors andtransporters. Alcohol enhancesγ-aminobutyric acid A (GABAA)receptors, and inhibits N-methyl-D-asparate (NMDA) receptors.In vitro studies suggest that theadditional effects involve theinhibition of adenosine uptake, anda translocation of the cyclic AMP-dependent protein kinase catalyticsubunit from the cytoplasm to thenucleus. Neurons adapt quickly tothese actions, and thus differenteffects may be present duringchronic administration andwithdrawal10.

Approximately 35% of drinkersmay experience a “blackout” (anepisode of temporary anterogradeamnesia), in which the person

forgets all or part of what occurredduring a drinking evening. Anothercommon problem, one seen afteras few as one or two drinks, is thatwhile alcohol can help someoneto fall asleep, it also “fragments”the sleep pattern causingalterations between sleep stagesand a deficiency in deep sleep. Atthe same time, alcohol diminishesrapid eye movement sleep early inthe night, resulting in prominentand sometimes disturbing dreamslater in the night. Finally, alcoholrelaxes the muscles in the pharynx,which can cause snoring andexacerbate sleep apnea10.

The symptoms characteristicof the hangover usually commenceseveral hours after the last ingestionof alcohol and peak at the time theBAC reaches zero. Epidemiologicaldata suggests that approximately75% of those who drink tointoxication will experiencehangover symptoms. Alcoholdirectly irritates the stomach lining.It also causes increased productionof HCl, most likely by causingincreased blood flow to the oxynticcells that secrete HCl. The afferentnerves of the vagus, andsympathetic innervation of thestomach relay this information tothe vomiting center of themedulla, which then sends downmotor stimulation to start theantiperistaltic waves necessary forpropulsion of the stomach contentsout of the mouth. Nausea is the“conscious recognition ofsubconscious excitation in an areaof the medulla closely associatedwith the vomiting center”,commonly seen in hangover11. Theetiology of hangover headaches is

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PartySmart Compared drug

Figure 1. BMI of the “PartySmart” and “Compared drug”groups.

*t = 1.146, R2 = 0.1411, p = 0.2848; NS

*


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uncertain, but it is thought that thevasodilation effect of alcohol leadsto increased pressure in the cranialcavity. Alcohol may also induceincreased histamine and serotoninlevels, which are correlated withheadaches in some people. Alcoholdecreases blood sugar level inmany people, and this temporaryhypoglycemia is thought to be aminor cause of the fatigueexperienced during a hangover.Both insulin and glucagon levelsare increased by acute alcoholingestion, the exact mechanismby which these two antagonistsreduce the availability of glucoseafter alcohol ingestion is unknown.This is more likely the major causeof hangover fatigue. Besides, theobvious fact that most recreationaldrinking occurs at night, prolongsthe time until a person begins sleep,and hence alcohol-induced sleepmay be of poorer quality due to the“rebound effect”12.

Alcohol depresseshypothalamic synthesis of

vasopressin (antidiuretic hormone,or ADH) as well as secretion of thishormone by the posterior pituitary.Anti-diuretic hormone combineswith membrane receptors on thesurfaces of kidney tubular cells toinduce a cyclic adenosinemonophosphate (cAMP) pathway.This ultimately results in therecruitment of special aquaporin

proteins to the surface of thetubular cells. Water can then bereabsorbed from the lumen of thetubule and preserved. This isespecially important in thecollecting duct, which is normallyimpermeable to water. Whenalcohol depresses the amount ofantidiuretic hormone in thecirculation, the kidneys fail toretain water and the personexcretes large volumes of urine(polyuria). This can lead to drynessof the mouth and mucousmembranes throughout the body.This can elicit an extreme thirstresponse (polydypsea) in order tostimulate the person to intakeliquids to compensate for the lossof f luid through the urine.Aldosterone and renin levels riseduring the hangover period to helpcombat the dehydration broughton by the inhibition of antidiuretichormone13.

Congener refers to any otherbiologically active compoundfound in alcoholic beverages, and

220200180160140120100

806040200

Alc

ohol

(ml)


Figure 2. Predefined amount of alcohol consumed to inducehangover in the “PartySmart” and “Compared drug” groups.

3.0

2.5

2.0

1.5

1.0

0.5

0PartySmart Compared drug

Figure 3. Severity of mean hangover score in the“PartySmart” and “Compared drug” groups.

Mea

n ha

ngov

er s

core

*t = 0.00, R2 = 0.00, p = 1; NS

*t = 3.578, R2 = 0.6154, p = 0.0072; S

*

*


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congeners contribute to bodydamage brought about by heavydrinking. Congeners include low-molecular-weight alcohols (e.g.,methanol and butanol), aldehydes,esters, histamine, phenols, tannins,iron, lead and cobalt. Thesechemicals contribute to hangovers.Beverages that have few congeners(gin and vodka) produce less severehangovers than those that containmany (whiskey, brandy and wine).Methanol is present in whiskey,brandy and red wine and ismetabolized by the same enzymesas ethanol, only slower because itis competitively inhibited by thepresence of ethanol, which has ahigher affinity for the enzymes. Itis thought that this lingeringmethanol may induce even greaterincreases in histamine, resultingin more severe headaches than inother hangovers14.

The only true preventativemeasure for a hangover is not toconsume alcohol in the first place.However, if this is not an option,

one may be able to reduce theseverity of the hangover by payingattention to the amount and typeof alcohol they consume. After ahangover has happened, however,researchers suggest that time is thebest remedy. Consumption offructose-containing foods andliquids will restore blood sugar andfluid levels and may help

overcome the fatigue anddehydration of the hangover.Antacids can relieve the irritationof the stomach lining and alleviatenausea. Nonsteroidal anti-inflammatory drugs may reduceheadache, but should be usedcautiously. Consuming “the hairoff the dog that bit you” i.e., morealcohol, will depress brain functionand may help with the irritabilitydue to rebound, but will ultimatelyonly prolong the hangover15.

This study used the POMSquestionnaire, which wasdeveloped in 1971, for peopleundergoing counseling orpsychotherapy, and it quicklygained popularity. The objectiveof POMS is to measure the effectsof various therapeutic approacheson mood. The POMS questionnaireis used extensively in athletics toevaluate the impact of trainingand to control overtraining.Increases in training load areassociated with a decrease in vigorand increase in fatigue, and these

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Blo

od a

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(mg/

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Figure 4. Blood alcohol levels after 2 hours in the“PartySmart” and “Compared drug” groups.

9876543210


Figure 5. Blood alcohol levels after 10 hours in the“PartySmart” and “Compared drug” groups.

Blo

od a

lcoh

ol le

vels

(mg/

dl)

*t = 0.9253, R2 = 0.09668, p = 0.3819; NS

*t = 4.817, R2 = 0.7436, p = 0.0013; S

*

*


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two states exhibit the largest andfastest change in response tostaleness. Additionally, mooddisturbance increases withdecreased performance andincreased muscle soreness7.

In an experimental study,“PartySmart” was evaluated for itseffects on hepatic alcoholicmetabolizing enzyme parameters,in rats. The first group receivedwater as vehicle, for 3 days, whilethe second group receivedPartySmart, for the same duration.One hour after the respectiveassigned treatments the animalswere euthanised, l iverhomogenized samples wereprepared and centrifuged. Theresultant supernatants were usedfor the estimation of hepaticalcohol, and ALDH usingspectrophotometric method. Theresults showed that pretreatmentwith “PartySmart” showed a highlysignificant increase in ADH, andALDH as compared to control16.

In another study, theadministration of “PartySmart”caused higher blood alcohol levels

at 2 hours, (possibly by inhibitingthe presystemic metabolism ofalcohol), and the bloodacetaldehyde levels were alsofound to be higher. The rapidlowering of acetaldehydeconcentration in the blood isreflected in significantly higherexcretion of acetaldehyde in theurine over a 10-hour period17.

In previous studies withPartySmart, lower alcoholand higher acetaldehyde

concentrations were reported inchronic alcohol users, and onestudy confirmed that regular usersof alcohol had lower blood alcoholconcentrations. This wasinterpreted to signify the inhibitionof the presystemic metabolism ofalcohol, as chronic ingestion ofalcohol causes induction ofenzymes involved in alcoholmetabolism. The same studyevaluated the cognitive functionsafter a standard drinking sessionbefore and after treatment for2 weeks with a similar herbalformulation, and cognitivefunctions showed less impairmentafter drug pretreatment. Thesefindings suggest that the rapidelimination of acetaldehyde mightbe responsible for this effect18,19.

These results also suggest that“PartySmart” prevents the bindingof acetaldehyde to cell proteins,causing a higher initial blood leveland a subsequent rapid elimination.Lower levels of alcohol andacetaldehyde in the blood at 10hours were reflected in the

250225200175150125100

7550250


Figure 6. Blood acetaldehyde levels after 2 hours in the“PartySmart” and “Compared drug” groups.

Blo

od a

ceta

ldeh

yde

leve

ls (µ

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)

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Figure 7. Blood acetaldehyde levels after 10 hours in the“PartySmart” and “Compared drug” groups.

Blo

od a

ceta

ldeh

yde

leve

ls (µ

g/dl

)

*t = 5.754, R2 = 0.8054, p = 0.0004; HS

*t = 3.679, R2 = 0.6285, p = 0.0062; S

*

*


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33

decreased symptom scores and thechange in the visual analog score.These observations are indicativeof a reduced hangover after“PartySmart” pretreatment. In theother drug group, increase in POMSscores for mood states indicatedthat the alcohol challenge had theanticipated effect.

In this study, there were noclinically significant adversereactions either observed byinvestigators or reported by thevolunteers in the “PartySmart”group, which indicates theexcellent safety profi le of“PartySmart”. “PartySmart” wasalso evaluated for acute andchronic toxicity, in vitro, and wasfound to be safe. The acute toxicityof “PartySmart” was evaluatedin vitro , and one group wasreceived 20 ml/kg body weight ofwater orally (control), while theother group received a single oraldose of “PartySmart” at 5000 mg/kg body weight, by gavage using astomach tube. All the rats wereobserved for changes in skin and

fur, eyes and mucous membranes,respiratory, circulatory and centralnervous system, tremors andconvulsions, salivation anddiarrhea, and lethargy, sleep andcoma. Necropsy of all the animalswas carried out, and all grosspathological changes wererecorded. There was no mortalityobserved in any of the “PartySmart”treated group, and general behaviorand appearance of the animals

were normal even at a dose of5000 mg/kg body weight, andhence it was not possible todetermine the median lethal dose(LD

50). There were no observable

gross abnormalities that could beattributed to drug toxicity at thetime of autopsy, and these findingsconfirm that “PartySmart” lackstoxicity following acute exposurein rats16.

The subchronic toxicity of“PartySmart” was evaluatedin vitro, and the control groupreceived 10 ml/kg body weight ofvehicle (water), while the othergroup received “PartySmart” at adose of 1000 and 2000 mg/kg bodyweight. All the experimentalanimals were observed for generalsigns and symptoms of toxicity.The blood samples were collectedbefore autopsy for hematologicaland biochemical parameters. Onday 91, the surviving animals weresacrificed after an overnight fast,and all the organs were preserved,processed, sectioned and stainedfor routine histopathological

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Figure 8. Urine alcohol levels after 2 hours in the“PartySmart” and “Compared drug” groups.

Uri

ne a

lcoh

ol le

vels

(mg/

dl)

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Figure 9. Urine alcohol levels after 10 hours in the“PartySmart” and “Compared drug” groups.

Uri

ne a

lcoh

ol le

vels

(mg/

dl)

*t = 2.425, R2 = 0.4236, p = 0.0415; S

*t = 4.463, R2 = 0.7134, p = 0.0021; S

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examination. No changes in feedintake were observed in the“PartySmart” treated group ascompared to control, whilehematological and biochemicalparameters were within normalrange in all the drug treated groups.No gross abnormalities attributingto the drug toxicity were noticedin any of the test groups. There wasno significant difference in theorgan weight profile of the animalsin the treated group as comparedto control. Histopathologicalexamination of all target organsshowed no evidence of lesionsattributing to drug toxicity. Thesefindings confirm that “PartySmart”is completely devoid of toxicityeven after repeated administrationin rats17.

ConclusionConclusionConclusionConclusionConclusionAlcohol-induced hangover is

a poorly understood physiologicalmanifestation of the biochemicaleffects of alcoholic beverages onthe body. There are various otherformulations, which are beingpromoted as a cure for

alcohol-induced hangover, butthe tall claims made by theseformulations have not beensubstantiated with evidencegenerated in controlled clinicaltrials. This study was planned toevaluate the comparative efficacyand safety of “PartySmart” in theprevention of the alcohol-inducedhangover symptoms, with one ofthe formulations promoted as acure for alcohol-induced hangover.

This study observed asignificant difference in the meanfinal hangover score, which wassignif icantly lower in the“PartySmart” group than in thecompared drug group. There was asignificant difference in the meanblood alcohol levels after 10 hours,a highly significant difference inthe mean blood acetaldehydelevels after 2 hours and a significantdifference after 10 hours, in boththe groups. There was a significantdifference in the mean urinaryalcohol levels after 2 and 10 hours,in both the groups. There was alsoa significant difference in the meanurinary acetaldehyde levels after2 and 10 hours, in both the groups.There were no clinically significantadverse reactions, either observedby the investigators or reported bythe volunteers in the both groupsand the overall compliance wasgood. These results suggest that“PartySmart” prevents the bindingof acetaldehyde to cell proteins,causing a higher initial blood leveland a subsequent rapid elimination.

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Figure 10. Urine acetaldehyde levels after 2 hours in the“PartySmart” and “Compared drug” groups.

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yde

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ls (µ

g/dl

)

70

60

50

40

30

20

10

0PartySmart Compared drug

Figure 11. Urine acetaldehyde levels after 10 hours in the“PartySmart” and “Compared drug” groups.

Uri

ne a

ceta

ldeh

yde

leve

ls (µ

g/dl

)

*t = 3.034, R2 = 0.535, p = 0.0162; S

*t = 4.337, R2 = 0.7016, p = 0.0025; S

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Lower levels of alcohol andacetaldehyde in the blood werereflected in the decreased finalhangover score. Therefore, it maybe concluded that “PartySmart” iseffective and safe for usage in theprevention of alcohol-inducedhangover.

ReferencesReferencesReferencesReferencesReferences1. Helen D, Belmont and Teen Ink.

The Young Authors Foundation,Inc. www.teenink.com/Past/1989/68.html

2. Marc A Schuckit. Alcohol andalcoholism. ht tp: / /www.harrisonsonline.com

3. Prabhakar B andVenkataramanappa PV. A studyof PartySharp in prevention ofhangover and in elimination ofacetaldehyde. The Antiseptic2001;98(6):206-209.

4. Prabhakar B and Kolhapure SA.Evaluation of efficacy and safety of“PartySmart” in preventing alcohol-induced hangover. MedicineUpdate 2004;11(12):55-60.

5. Shalini, Ramakrishna, Manu MBand Kolhapure SA. Evaluation ofefficacy and safety of PartySmart inthe prevention of alcohol-inducedhangover: A prospective,randomized, double bl ind,comparative, phase III clinical trial.

Indian J. Clin. Pract. 2004;15(7):25-40.

6. Selzer ML, Vinokur A and vanRooijen L. A self-administered shortMichigan Alcohol Screening Test(MAST). J. Stud. Alcohol. 1975;36:117-126.

7. Lloyd A, Gandevia S, Brockman A,Hales J and Wakefield D. Cytokineproduction and fatigue in patientswith chronic fatigue syndrome andhealthy control subjects inresponse to exercise. Clin. Infect.Dis. 1994;18(Supp. 1):S142-S146.

8. McNair M, Maurice Lorr and Leo F.Profile of mood states, bi-polarform/Douglas. Droppleman. SanDiego, CA: EDITS, 1980-1988.http://www.lib.uchicago.edu/e/su/tests/newfy99.html.

9. Collins SL, Moore RA and McQuayHJ. The visual analogue painintensity scale: What is moderatepain in millimeters? Pain 1997;72:95-97.

10.Harrison’s Principles of InternalMedicine Version 1.0, 5th Edition,A division of The McGraw-HillCompanies, ISBN 0-07-048646-8.

11.Guyton and Hall. Textbook ofMedical Physiology WB SaundersCompany, Philadelphia 2000:732-733,758,768-769.

12.Wiese, Jeffery G, Michael G Shlipakand Warren S Browner. AlcoholHealth and Research World.

Alcohol Hangover: Mechanismsand Mediators 2000:54-60.

13.Wiese, et al. The alcohol hangover.Annals of Internal Medicine2000;132:897-902.

14.Chemical of the week: Ethanol.Accessed via ht tp: / /scifun.chem.wisc.edu/chemweek/ethanol/ethanol.html.

15.Freudenrich and Craig. HowAlcohol Works. Accessed via http:// w w w . h o w s t u f f w o r k s . c o m /alcohol.htm. Intoximeters, Inc.2001. “Alcohol and the humanbody.”

16.Data on file, R&D Centre, TheHimalaya Drug Company,Bangalore, India.

17.Acute and chronic toxicity study ofPartySmart (In-house study), R&DCenter, The Himalaya DrugCompany, Bangalore, Data on file,2003.

18.Chauhan BL and Kulkarni RD. Doseresponse of alcohol after chronicadministration of alcohol and effectof Liv.52 on blood, liver alcoholand acetaldehyde levels in rats. XIInt. Cong. Pharmacol. July 1-6,1990 Amsterdam.

19.Kulkarni RD and Chauhan BL.Bioavailability of alcohol from sixdifferent alcoholic beverages andthe effect of Liv.52. XI Int. Cong.Pharmacol. July 1-6, 1990Amsterdam.

Improvement Should Begin at the Diagnostic LevelMeasures to improve sputum microscopy should be taken.

Check the quality of microscopy.

We need cultural sensitivity labs all over the country.

Twenty-four centers have already been proposed with the help of World Bank.

Measures taken should include people inflicted with TB at the field levels.

Unless we ensure correction of the existing DOTS program, DOTS plus would not be a success.

Relapse in HIV-TB has mainly been seen through a new infection than relapse of an existinginfection. Therefore, it is a case of mistaken relapses.

This would encourage doctors to focus on patient and persistent relapses may be avoided.

Ongoing active transmission reports are encouraging, ensuring better patient treatment.

Source: Rajeshwari Ramachandran. 59th National Conference of Tuberculosis and Chest Diseases(NATCON 2005) New Delhi 2005 3-6 Feb.

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