Published as: Verster JC. The alcohol hangover: a puzzling phenomenon. Alcohol &
Alcoholism 2008, 43: 1-3
Many people favour the (unproven) popular belief that dehydrationis the main cause
of alcohol hangover symptoms. However, takinga closer look at the present research
on biological changesduring alcohol hangovers suggests otherwise. A limited numberof experiments have studied biological changes that are presentthe day after excessive
drinking (for a review, see Ylikahriand Huttunen, 1977). Significant changes were
reported on endocrineparameters (increased concentrations of vasopressin, aldosterone,and renin) and metabolic acidosis (reduced blood pH values dueto increased concentrations
of lactate, ketone bodies, and freefatty acids). These effects are related to dehydration
and causesymptoms such as dry mouth and thirst. In addition, changesin immune system
parameters (increased concentrations of pro-inflammatorycytokine [IL-12] and interferon-gamma
[IFN]) have been reported(Kim et al., 2003). It is likely that these changes in
immunesystem parameters cause the more ‘cognitive’ alcoholhangover effects such
as memory impairment and mood changes.Moreover, these findings suggest that alcohol
hangover and dehydrationare two independent yet co-occurring processes that have
differentunderlying mechanisms. The idea that alcohol hangover symptoms(i.e. memory
impairment) are related to immune system activationis strengthened by a relatively
new discovery that the immunesystem and central nervous system (CNS) operate in
close communicationwith each other (Maier and Watkins, 1998; Maier, 2003).
The first line of evidence for the hypothesis that effects ofimmune activity on
the CNS may be the cause of alcohol hangovercomes from studies showing that cytokines
communicate with thebrain. The nervus vagus pathway is the main afferent pathwaymediating the effects of peripherally released cytokines inthe CNS (Dantzer et al.,
1998). Peripherally released cytokinesthus have central effects, by signaling the
brain to up-regulatecerebral cytokine production (Parnet et al., 1994). Cytokinereceptors have been localized on glia cells and neurons throughoutthe brain, but
are especially dense in the hippocampus, a brainstructure that is vital in memory
Second, the effects caused by cytokines are very similar tothe core symptoms of
alcohol hangover, suggesting that underlyingprocesses might be the same. Cerebral
cytokines (IL-1ß,IL-6, and tumour necrosis factor [TNF-]) are involved in sicknessbehaviour (Dantzer et al., 1998). In animals, symptoms of sicknessbehaviour include
weakness, inability to concentrate, decreasedappetite, reduced activity, sleepiness,
and loss of interestin usual activities. In humans, the same symptoms are all commonlyreported during alcohol hangover.
Third, in humans, a relationship between the presence of cytokinesand memory impairment
has been demonstrated (Reichenberg etal., 2001). Endotoxin, injected to provoke
sickness behaviourin healthy volunteers significantly increased cytokine concentrations(IL–1ß, IL-6 and TNF-). Psychomotor functioning andattention were not affected,
but memory was significantly impairedon a word learning test, story recall test,
and figure recalltest up to 10 h after injection. Thus, the effects on memoryfunctioning
during sickness behaviour are strikingly similarto those observed during alcohol
There have been a few studies that proposed that dehydrationitself is a cause of
memory impairment (e.g. Cian et al., 2001;Tomporowski, 2003; Lieberman et al., 2005).
However, intensestressors (e.g. simulated combat or heavy prolonged exercise)were
used to cause dehydration. Hence, it can be argued thatthese stressors have mobilized
the immune system that in returncauses memory impairment, independent of the dehydration
effectsthat accompany these stressors. In support for this idea, inpassive circumstances
without a stressor (e.g. using abstinencefrom water for 11 h) no significant effects
were reported ontests examining memory functions (Neave et al., 2001). Thus,these
findings support the hypothesis that not dehydration,but a stressor causes an immune
response which results in memoryproblems. Future research should verify this hypothesis.
In this issue of Alcohol & Alcoholism, the article by Stephensand colleagues clearly
discusses the difficulties and pitfallsof hangover research. Hangover research showed
conflicting results:half the studies report significant performance effects whereasthe other half do not. The most important cause of this is thefact that the pathology
of alcohol hangover has not been elucidated.This is illustrated by the fact that
whereas numerous hangovercures are available, only few of them are scientifically
investigatedand none of them prevents or relieves hangovers in a significantway
(Pittler et al., 2005). Since the biology of hangovers isnot well understood, it
is not surprising that the design ofexperiments and the included psychological tests
lack an evidence-basedrationale.
Blinding, i.e. preventing participants from knowing which isthe hangover or placebo
test day, is especially difficult inalcohol hangover research. Considerable amounts
of alcohol (>1.0 g/kg) need to be consumed to produce a hangover. Alcoholintoxication
and its after-effects are impossible to mimic bya placebo condition. Hence, participants
can easily recognizethe hangover and placebo condition. Alcohol (hangover) expectanciesmay thus affect performance. The authors address this shortcomingto naturalistic
experiments, but due to blinding difficultiesthis is equally true for laboratory-controlled
As pointed out by Stephens and colleagues, the small samplesize of many hangover
experiments is another issue that resultedin conflicting results. Several studies
tested less than 10subjects, and thus, do not have enough statistical power todraw
strong conclusions from the outcome measures. Moreover,in most studies only young
healthy men participated. It is wellknown that men and women differ in alcohol metabolism,
and thus,may differ in the presence and severity of hangover symptoms.More recent
studies (Verster et al., 2003; McKinney et al.,2004) acknowledged this and did use
larger groups of subjectsconsisting of both men and women.
To make matters complicated, the presence and severity of alcoholhangovers is influenced
by many factors other than the amountof alcohol. One is these factors is the presence
of congenersin alcoholic drinks. Congeners are substances that flavour andcolour
drinks. In laboratory experiments mixing pure alcoholwith orange juice can prevent
the presence of congeners. However,in real life (and naturalistic experiments) people
consume avariety of different alcoholic drinks which all have differentcongener
content. Stephens and colleagues shortly discuss theimpact of congeners on performance
measures during alcohol hangover,but acknowledge that not much research has been
done in thisarea. As summarized in Figure 1, it can be concluded that alcoholicdrinks that contain more congeners produce more severe alcoholhangovers. Moreover,
a recent survey showed it takes fewer high-congenerdrinks to get a hangover, while
at the same time the severityof these hangovers is most pronounced (Verster, 2006).
Fig. 1 Number of drinks that produce a hangover and the reported corresponding hangover
severity for beer, wine and liquor.Hangover severity ranges from 0 (no hangover)
to 8 (extreme hangover). Significant differences (P < 0.05) are indicated by *. Note:
In The Netherlands a standardized drink of beer, wine or liquor all contain the same
amount of alcohol.
A second factor that is often not incorporated in research isthe effect of sleep
duration and quality on the hangover state.Whereas in laboratory studies participants
are often alloweda full night of sleep, in real life drinking time often goesat
the expense of sleep time. The results of a recent survey,summarized in Figure 2,
show that some of the symptoms thatare experienced the day after excessive drinking
are significantlyrelated to sleep duration and quality and not to the amountof
alcohol that was consumed (Verster and Roehrs, 2007). Theresulting daytime sleepiness
is significantly related to severalaffects that are generally ascribed to be alcohol
Fig. 2 Schematic representation of the relationship between individual hangover
symptoms and sleep quality, daytime sleepiness and alcohol quantity. Please note
that only alcohol quantity and daytime sleepiness correlated significantly with overall
hangover severity. All depicted correlations were significant (P < 0.05), except
vomiting (P < 0.06) and guilt (P < 0.07).
The results from this survey underline the fact that many factorsinfluence the hangover
state. On the other hand, it is essentialto keep in mind that several factors co-occur
with the hangoverstate including dehydration effects and sleep deprivation. Disentanglingthese factors is very important and requires future research.Other factors such
as the impact of food and smoking on hangoverseverity also deserve attention from
hangover researchers. Althoughit is of scientific interest to investigate these
factors inisolation, in real life they are experienced together. Therefore,the
importance of naturalistic studies in which subjects canfreely drink, smoke, and
eat is evident.
Although there are many methodological shortcomings in alcoholhangover research,
it is evident that alcohol hangovers do havean impact on daily activities such as
on-the-job performance.This is illustrated by a study of Ames et al. (1997).
They conducted structured interviews among 800 assembly workersin order to examine
the relationship between hangovers and work-relatedproblems. Although less than
half the workers reported beingat work while having a hangover, those who experienced
hangoversreported significantly often feeling sick at work, been criticizedby a
supervisor, having conflicts or fights with co-workers,had significantly more problems
in completing the job, and reportedfalling asleep more often at work. Statistical
analyses showedthat having a hangover during work actually predicts these work-relatedproblems: the frequency of problems increases when people moreoften reported having
hangovers at work.
Interestingly, no significant differences were found in absenteeismbetween workers
reporting hangovers and those who did not. Apossible explanation may be that workers
with a hangover feelthat having a hangover is ‘their own fault’, andthe obligation
they have to go to work may prevent calling sick.The fact that workers do go to
work when having a hangover isof concern, especially since some in jobs making the
wrong decisionsmay have serious consequences.
The article by Stephens and colleagues calls for additionalhangover research, using
more sophisticated research methods.In this context, researchers should ask themselves
the question‘what is the alcohol hangover?’. It is evident thatbesides the alcohol
amount many other factors play a role indetermining the presence and severity of
hangovers. To complicatematters, co-occurring dehydration and sleep deprivation
havean impact on the next-day effect of excessive alcohol consumptionas well. Until
future research elucidates its pathology, thealcohol hangover remains a puzzling
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Cian C., Barraud P. A., Melin B., et al. Effects of fluid ingestion on cognitive
function after heat stress or exercise-induced dehydration. International Journal
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Dantzer R., Bluthe R.-M., Laye S., et al. Cytokines and sickness behavior. Annals
of the New York Academy of Sciences (1998) 840:586–590.
Kim D.-J., Kim W., Yoon S.-J., et al. Effects of alcohol hangover on cytokine production
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Lieberman H. R., Bathalon G. P., Falco C. M., et al. Severe decrements in cognition
function and mood induced by sleep loss, heat, dehydration, and undernutrition during
simulated combat. Biological Psychiatry (2005) 57:422–429.
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stress, pain and cognition. Brain Behavior and Immunity (2003) 17:69–85.
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Neave N., Scholey A. B., Emmett J. R., et al. Water ingestion improves subjective
alertness, but has no effect on cognitive performance in dehydrated healthy young
volunteers. Appetite (2001) 37:255–256.
Parnet P., Amindari S., Wu C., et al. Expression of type I and type II interleukin-1-receptors
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Pittler M. H., Verster J. C., Ernst E. Interventions for preventing or treating alcohol
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Stephens R., Ling J., Heffernan T.M., Heather N., Jones K. A review of literature
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The alcohol hangover develops when blood alcohol concentration(BAC) returns to zero
and is characterized by a feeling of generalmisery that may last more than 24 h.
It comprises a varietyof symptoms including drowsiness, concentration problems,
drymouth, dizziness, gastro-intestinal complaints, sweating, nausea,hyper-excitability,
and anxiety. The alcohol hangover is anintriguing issue since it is unknown why
these symptoms arepresent after alcohol and its metabolites are eliminated fromthe body.
Although numerous scientific papers cover the acute effectsof alcohol consumption,
researchers largely neglected the issueof alcohol hangover. This lack of scientific
interest is remarkable,since almost everybody is familiar with the unpleasant hangovereffects that may
arise the day after an evening of excessivedrinking, and with the
ways these symptoms may affect performanceof planned activities.