Am J Physiol Regulatory Integrative Comp Physiol
281: R52–R55, 2001.
The effect of alcohol consumption on the circadian
control of human core body temperature is time dependent
THIERRY DANEL,1,2 CHRISTIAN LIBERSA,3 AND YVAN TOUITOU2
Clinique de la Charité, Centre Hospitalier Régional Universitaire, 59037 Lille Cedex;
2
Service de Biochimie Médicale et Biologie Moléculaire Faculté de Médecine
Pitié-Salpêtrière, 75013 Paris; and 3Centre d’Investigation Clinique, Institut National de
la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire, 59037 Lille, France
1
Received 18 September 2000; accepted in final form 6 March 2001
alcoholism; circadian rhythm
psychoactive drug in Western countries and leads to somatic, psychic, and social
disorders. The chronobiological aspect of alcohol-related diseases has not been examined; however, if
alcohol alters biological rhythms, some complications
such as sleep or depression disorders, which are freALCOHOL IS THE MOST COMMON
Address for reprint requests and other correspondence: T. Danel,
Clinique de la Charité, Centre Hospitalier Régional Universitaire,
59037 Lille Cedex, France (E-mail: tdanel@nordnet.fr).
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quently associated with alcohol and are also known to
have a strong chronobiological determinant, may be
partly explained by a chronobiological approach. The
circadian temperature rhythm is one of the main indexes of 24-h synchronization and is essential for the
adaptation of humans to their environment. Only a few
controlled studies deal with the effect of alcohol on core
body temperature (12–14), and they examine single
doses of ethanol. No published studies report the effects of a 24-h consumption period, of the type found in
heavy drinkers. Two major problems arise in performing such a study. First, it is difficult to monitor temperature in alcoholics during the course of the disease
because of their poor compliance. Second, giving alcoholic beverages to abstinent patients is not ethically
acceptable. We therefore conducted a trial based on a
26-h alcohol consumption period with healthy volunteers. The total dose reached the amount generally
ingested by alcoholic patients, i.e., 256 g/day (corresponding roughly to 2.5 l of wine at 12° per cent, 700 ml
of whisky at 40° per cent, or 6 l of beer at 4.5° per cent),
administered at regular intervals during the trial. Rectal temperature was monitored throughout the trial to
study the circadian temperature cycle during alcohol
consumption compared with that during a control session.
METHODS
Subjects. Nine healthy men (Table 1) between the ages of
21 and 30 yr (23.3 6 2.9 yr) were included after obtaining
their informed written consent. Lifestyle, physical health,
and clinical status were assessed by routine clinical and
laboratory examinations to determine eligibility for the
study. All subjects were synchronized with diurnal activity
and nocturnal rest. Subjects had no physical abnormalities at
the time of examination. Body mass index ranged from 20 to
25. No subject had a current or past diagnosis of alcohol,
tobacco, or other substance abuse or dependence. They took
no medication, worked no rotating shifts, took no transmeridional flights, and had no infection or disease for at least
1 mo before the session. No subject had a current or past
depressive disorder or psychosis. All scores on the MontgomThe costs of publication of this article were defrayed in part by the
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0363-6119/01 $5.00 Copyright © 2001 the American Physiological Society
http://www.ajpregu.org
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Danel, Thierry, Christian Libersa, and Yvan
Touitou. The effect of alcohol consumption on the circadian
control of human core body temperature is time dependent.
Am J Physiol Regulatory Integrative Comp Physiol 281:
R52–R55, 2001.—The few controlled studies dealing with the
action of alcohol on core body temperature in humans have
focused on the effect of a single dose of ethanol and reported
that it has a hypothermic effect. No studies report the effects
of repeated ethanol intake over a 24-h period, a pattern of
consumption much closer to the clinical condition of chronic
alcoholism. We therefore designed a trial in which alcohol
was repeatedly and regularly administered, with a total dose
of 256 g. Nine healthy male volunteers (mean age 23.3 6 2.9
yr; range 21–30) each served as his own control. The circadian temperature rhythm was studied by a single-blind,
randomized, crossover study that compared a 26-h alcohol
session to a 26-h placebo session. The trial controlled for
so-called masking effects known to affect temperature. The
volunteers were in bed; the ambient temperature was maintained between 20 and 22°C. Meals were standardized. And
light was controlled during the night. All sessions took place
between November and April. The two sessions were separated by 2 to 5 wk. Rectal temperature was monitored every
20 min throughout the trial. We found the standard hypothermic effect of alcohol in the early hours of the trial, during
the daytime, but our principal result is that alcohol consumption induced a very significant hyperthermic effect (10.36°C)
during the night and thereby reduced the circadian amplitude of core body temperature by 43%. The dramatic decrease
of the amplitude of circadian temperature rhythm that we
observed may explain, at least in part, some clinical signs
observed in alcoholic patients, including sleep and mood
disorders. We suggest that jet lag, shift work, and aging,
which are known to alter body temperature, are aggravated
by alcohol consumption.
ALCOHOL CONSUMPTION AND BODY TEMPERATURE
Table 1. Subjects’ characteristics
Subjects
Age
Weight, kg
Body Mass
Index
Horne and
Ostberg Score
1
2
3
4
5
6
7
8
9
Means
22
23
21
26
21
22
22
23
30
23.3 6 2.9
70
75
61
78
74
64
70
78
68
70.8 6 5.9
21.6
23.1
20.2
22.8
24.8
20.8
22.7
24.7
21.5
22.5 6 1.6
39
54
52
54
41
43
52
59
52
49.6 6 6.8
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perature ranged from 20 to 22°C during the session. Blood
samples were collected every 6 h (1200, 1800, 2400, 0600, and
1200) for blood alcohol determination. When the blood samples were collected at 2400, the room was illuminated by light
with an average intensity of 50 lx.
Statistical analysis. All statistical analysis was performed
with SAS software (SAS Institute, Cary, NC). Statistically
significant differences between the alcohol and control sessions were determined with two-way, repeated-measures
ANOVA. A general linear mixed model for repeated data (9)
was used to assess the variations of temperature over time
and group. Then, statistical comparisons for each point of the
circadian temperature pattern were performed with the
paired Wilcoxon’s rank sum test.
RESULTS
Figure 1 displays typical temperature patterns in
the volunteers. Figure 2 reports the temperature patterns for the group during the control and alcohol
sessions, and Fig. 3 reports the BACs at five points
during the day, corresponding to the experimental protocol. Interaction (ANOVA) between the time factor
and group factor was significant (P , 0.0001). Each
time point of the temperature pattern during the alcohol session was compared with the corresponding point
in the control session by paired Wilcoxon’s rank sum
test. This comparison showed that the temperature
during the alcohol session was significantly higher at
night (P value ranging from 0.046 to 0.007 from 0300 to
0820) and significantly lower in the daytime, at the
beginning of the trial (P value ranging from 0.047 to
0.007 from 1240 to 1400). Before, between, and after
these hours, temperature did not differ significantly.
The mean lowest temperature was 0.36°C higher in the
alcohol session (mean value 36.48 6 0.18°C) than in
the control session (mean value 36.12 6 0.17°C). The
peak temperature in the alcohol session was 37.03 6
0.22°C, compared with 37.07 6 0.12°C in the control
session. Thus the reduction in the amplitude of the
Table 2. Experimental protocol
Alcohol
Administration
Total, g
Frequency, g/h
Route
1000–1100–1200 1300–2100
60
20
Oral
90
10
Oral
2200–0600
0700–1100
56
7
Intravenous
50
10
Oral
Fig. 1. Individual circadian patterns of core body temperature. F,
Alcohol session; E, control session. Top, subject 4; bottom, subject 7.
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ery and Asberg (10) depression-rating scale were lower than
18, which ruled out any current depressive disorder. No
subject had a current diagnosis of delayed or advanced phase
or hypernyctohemeral syndrome. Horne and Ostberg (7)
scores ranged from 39 to 59 (mean 49.5 6 6.8), a criterion
that excluded those who were “definitively morning” or “definitively evening” types. Routine blood counts and blood
chemistry were in the normal range, and HIV and hepatitis
B and C tests were negative.
Experimental protocol. The Ethics Committee of Lille,
France, approved the study. The circadian rhythm of core
body temperature was studied in nine healthy male volunteers during a single-blind, randomized, crossover study comparing a 26-h alcohol session and a 26-h placebo session. In
the alcohol session (Table 2), 256 g of ethanol were administered between 1000 the first day and 1200 on the second day
to obtain blood alcohol concentrations between 0.5 and 0.7 g/l
throughout the session. To obtain a significant blood alcohol
concentration (BAC) at the beginning of the data collection
(1200), 20 g of ethanol were administered orally at 1000,
1100, and 1200; then 10 g/h were administered from 1300 to
2100 and from 0700 to 1100 on the second day. The alcohol
administered was mixed with fruit juice. In the placebo
session, only fruit juice was administered. To enable subjects
to sleep while simultaneously maintaining a sufficient BAC,
7 g/h of alcohol (Curethyl*, AJC Pharma, Chateauneuf,
France) in saline solution were administered intravenously
during the night (between 2200 and 0600) in the alcohol
session and saline solution only in the control session. A
rectal probe (Squirrel Logger Equipment, Grant Instruments, Cambridge, UK) for recording core temperature was
inserted at 1200 and left in place throughout the monitoring
period. Rectal temperature was recorded every 20 min
throughout the 26-h experimental period. All the sessions
took place between November and April. For each subject,
the two sessions were separated by 2 to 5 wk. Subjects were
admitted to the Clinical Investigation Center at 0800. During
observation from 1000 on the first day to 1500 on the second
day, subjects were in bed, reading and watching television;
they ate standardized meals at 0800, 1200, and 1900 on the
first day and at 0800 and 1200 on the second day. They left at
1500. Lights were off between 2200 and 0600. Ambient tem-
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ALCOHOL CONSUMPTION AND BODY TEMPERATURE
Fig. 2. Circadian profiles of core body temperature (by 20 min)
of 9 healthy men studied twice: during an alcohol session (F)
(consumption of 256 g of alcohol administered regularly during
a 26-h period) and a control session (E). Temperature during
the alcohol session was significantly higher from 0300 to 0820
(P value between 0.046 and 0.007) and significantly lower in
daytime, at the beginning of the trial (P value between 0.047
and 0.007). At night, the mean lowest temperature value was
0.36°C higher in the alcohol session (36.48°C) than in the
control session (36.12°C). Horizontal white bars, lights on;
horizontal black bar, lights off.
DISCUSSION
Controlled studies of humans and other animals that
have dealt with the action of alcohol on core body
temperature focused on the effect of a single dose of
ethanol and considered it for a few hours after administration. These studies all concluded that alcohol has
a hypothermic effect. In humans, Reinberg et al. (13)
found that the circadian 24-h mean value of oral temperature decreased when a single dose of 0.67 g/kg was
administered at 0700 but was unaffected by the same
single dose when it was administered at 1100, 1900, or
2300. O’Boyle et al. (12) recorded oral temperature for
3 h after consumption of 0.8 ml/kg of alcohol at either
0800 or 1600. They observed an alcohol-induced decline in oral body temperature during the 0800 session
and no effect during the 1600 session. Yap et al. (14)
found a hypothermic effect during the 2 h following the
administration of 0.75 g/kg of alcohol at 0900, 1500,
2100, and 0300. Reports about rodents state that alcohol administration decreases body temperature (2),
and it has been hypothesized that ethanol induces a
downward shift of the set point for temperature control
(1, 5). Another suggested mechanism is that alcohol
suppresses thermoregulation (11).
Our study of the effects of alcohol on core body
temperature is, to our knowledge, the first circadian
study performed. It uses a standardized and sustained
administration to obtain experimental conditions close
to those experienced by alcoholic patients. So-called
masking effects known to affect temperature (6) have
been controlled throughout the trial. Volunteers were
in bed, ambient temperature was maintained from 20
to 22°C, meals were standardized, and light was controlled at night. All these parameters were similar in
both sessions. We found that alcohol consumption led
to a decrease in core body temperature at the beginning of the trial, in the daytime (between 1240 and
1400), a finding consistent with the standard hypothermic effect of alcohol reported in the literature, as described above. The principal finding of our study, however, is that alcohol consumption increased nocturnal
core body temperature. Indeed, in this study, we
clearly show that alcohol consumption dramatically
affected the circadian core body temperature by inducing its nocturnal increase (average increase of 0.36°C);
this resulted in an ;43% decrease in the amplitude of
the circadian temperature rhythm. Our data, obtained
on a circadian basis, strongly suggest that the effect of
alcohol on core body temperature is time dependent
and ultimately reduces the amplitude of the rhythm.
Fig. 3. Mean value of the blood alcohol levels (g/l) in 9 subjects, corresponding to the experimental protocol.
Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 9, 2017
circadian temperature rhythm between the two sessions (43%) is due to the higher low point during the
alcohol session, compared with the control session.
Seven of nine volunteers experienced a hyperthermic
effect at night.
ALCOHOL CONSUMPTION AND BODY TEMPERATURE
Perspectives
Our data strongly suggest that alcohol has a hyperthermic effect at night in humans. This could have
serious consequences, especially on mood and sleep.
Numerous studies have reported that circadian temperature amplitude decreases in mood disorders (3)
and that sleep is strongly linked to temperature
rhythm (8). The dramatic decrease of the amplitude of
circadian temperature rhythm that we observed may
explain, at least in part, some clinical signs observed in
alcoholic patients, including sleep and mood disorders.
Our data suggest that alcohol consumption exacerbates the tendency toward flattening of the circadian
temperature curve and consequently intensifies sleep
and mood disorders. Similarly, we suggest that the
pathophysiological conditions, including mood and
sleep disorders, jet lag, shift work, and aging, that are
known to result in alteration of temperature, are aggravated by alcohol consumption. Further data on alcoholic patients are needed to verify these hypotheses.
We thank Dr. A. Duhamel (Centre d’Etudes et de Recherche en
Informatique Médicale, Lille) for statistical analysis.
This work was supported by grants from Institut National de la
Santé et de la Recherche Médicale, Centre Hospitalier Régional
Universitaire of Lille, and Institut de Recherches Scientifiques sur
les Boissons.
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Another explanation should be considered in light of
Gallaher and Egner’s (4) report on rodents. They studied the temperature effects of ethanol injection at 0900
(during the rest period) at doses ranging from 2 to 6
g/kg. They observed a hypothermic effect but also rebound hyperthermia during the successive rest periods
and persisting for several days. They hypothesized a
mild abstinence syndrome or alternatively a disruption
of the normal circadian temperature rhythm. Because
blood alcohol levels were lower during the night than
the day in our experiment, a sympathetic rebound
associated with withdrawal cannot be excluded. Further experiments are needed however to confirm this
hypothesis. Despite the lack of confirmation, we nonetheless find the time-dependent hypothesis more plausible, because hyperthermia in withdrawal is generally
observed after long periods of alcoholism and because
our subjects were not alcoholic.
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