Water-Induced Thermogenesis

Abstract

Drinking lots of water is commonly espoused in weight loss regimens and is regarded as healthy; however, few systematic studies address this notion. In 14 healthy, normal-weight subjects (seven men and seven women), we assessed the effect of drinking 500 ml of water on energy expenditure and substrate oxidation rates by using whole-room indirect calorimetry. The effect of water drinking on adipose tissue metabolism was assessed with the microdialysis technique. Drinking 500 ml of water increased metabolic rate by 30%. The increase occurred within 10 min and reached a maximum after 30-40 min. The total thermogenic response was about 100 kJ. About 40% of the thermogenic effect originated from warming the water from 22 to 37 C. In men, lipids mainly fueled the increase in metabolic rate. In contrast, in women carbohydrates were mainly used as the energy source. The increase in energy expenditure with water was diminished with systemic beta-adrenoreceptor blockade. Thus, drinking 2 liters of water per day would augment energy expenditure by approximately 400 kJ. Therefore, the thermogenic effect of water should be considered when estimating energy expenditure, particularly during weight loss programs.

Full text

Water-Induced Thermogenesis
MICHAEL BOSCHMANN, JOCHEN STEINIGER, UTA HILLE, JENS TANK, FRAUKE ADAMS,
ARYA M. SHARMA, SUSANNE KLAUS, FRIEDRICH C. LUFT,
AND JENS JORDAN
Franz-Volhard Clinical Research Center and Helios-Klinikum-Berlin (M.B., J.S., J.T., F.A., A.M.S., F.C.L., J.J.), Medical
Faculty of the Charite´, Humboldt-University, D-13125 Berlin, Germany; German Institute of Human Nutrition (U.H., S.K.),
D-14558 Potsdam-Rehbru¨ cke, Germany; and McMaster University (A.M.S.), Hamilton General Hospital, L8L 2X2 Hamilton,
Ontario, Canada
Drinking lots of water is commonly espoused in weight loss
regimens and is regarded as healthy; however, few systematic
studies address this notion. In 14 healthy, normal-weight sub-
jects (seven men and seven women), we assessed the effect of
drinking 500 ml of water on energy expenditure and substrate
oxidation rates by using whole-room indirect calorimetry.
The effect of water drinking on adipose tissue metabolism was
assessed with the microdialysis technique. Drinking 500 ml of
water increased metabolic rate by 30%. The increase occurred
within 10 min and reached a maximum after 30– 40 min. The
total thermogenic response was about 100 kJ. About 40% of the
thermogenic effect originated from warming the water from
22 to 37 C. In men, lipids mainly fueled the increase in met-
abolic rate. In contrast, in women carbohydrates were mainly
used as the energy source. The increase in energy expenditure
with water was diminished with systemic
␤
-adrenoreceptor
blockade. Thus, drinking 2 liters of water per day would aug-
ment energy expenditure by approximately 400 kJ. Therefore,
the thermogenic effect of water should be considered when
estimating energy expenditure, particularly during weight
loss programs. (J Clin Endocrinol Metab 88: 6015– 6019, 2003)
“D
RINK LOTS OF water and keep yourself on sched-
ule” is an old health adage. Nevertheless, few data
underscore this homily. Recent studies have demonstrated
that drinking water is, indeed, associated with a substantial
physiological response. For example, water drinking in-
creases systolic blood pressure more than 30 mm Hg in
patients with severe autonomic failure. The pressor response
was apparent within 5 min, reached a maximum after ap-
proximately 35 min, and was sustained for more than 60 min
(1, 2). Water drinking increases blood pressure moderately in
older but not younger control subjects (2). The pressor re-
sponse may be mediated by the sympathetic nervous system
(2–4). In healthy subjects, water drinking increases muscle
sympathetic nerve traffic (3) and venous plasma norepineph-
rine concentrations (2, 3, 5). Furthermore, the pressor re-
sponse can be abolished with systemic ganglionic blockade
(2). The sympathetic nervous system is important in regu-
lating energy metabolism and fuel utilization. Sympathetic
activation increases cellular glucose uptake and metabolism
and stimulates lipolysis (6). We tested the hypothesis that the
sympathetic stimulus provided by water drinking might in-
crease metabolic rate. Moreover, we determined the effect of
water drinking on fuel mobilization and utilization system-
ically and at the adipose tissue level in normal men and
women. Finally, we reasoned that the metabolic water effect
might be attenuated with systemic or locally applied
␤
-
adrenoreceptor blockade.
Subjects and Methods
Subjects
Fourteen healthy subjects [seven men: age, 29 ⫾ 3 yr; body mass index
(BMI), 24.20 ⫾ 0.94 kg/m
2
; seven women: age, 27 ⫾ 2 yr; BMI, 20.80 ⫾
0.88 kg/m
2
; P ⬍ 0.05 for BMI] participated in the metabolic studies. In
eight healthy subjects (two men and six women; age, 25 ⫾ 1 yr), we
determined the effect of water drinking on plasma osmolarity. All sub-
jects were drug-free and nonsmoking. The institutional review board
approved all studies, and written informed consent was obtained before
study entry.
Protocol
Subjects did not eat 12.5 h before and did not drink 1.5 h before testing.
Three separate studies were conducted. In the first study, we assessed
the effect of drinking 500 ml of water on energy expenditure and sub-
strate oxidation rates by using indirect calorimetry. In the second study,
we used the microdialysis technique to characterize the effect of drinking
500 ml of water on adipose tissue blood flow and metabolism. In a
subgroup, studies were conducted twice, once after ingestion of placebo
and once after ingestion of 100 mg of the
␤
-adrenoreceptor blocker
metoprolol (Stada Arzneimittel AG, Bad Vilbel, Germany). The medi-
cations were ingested in a single-blinded fashion 1 h before water drink-
ing. In the third study, we determined venous plasma osmolarity at
baseline and 30 and 60 min after water drinking.
Calorimetry
Oxygen uptake and carbon dioxide production were measured by
using a respiratory chamber to assess changes in energy expenditure,
respiratory quotient (RQ; CO
2
produced/O
2
consumed), and carbohy-
drate and lipid oxidation rates, respectively. In previous studies in 16
healthy subjects, the maximal spontaneous change in metabolic rate over
a 3-h period was 0.2 ⫾ 0.09 kJ/min (3%). Throughout the study, subjects
remained seated. After a run-in period of 15 min, resting energy ex-
penditure was determined for 30 min. Then, the subjects ingested 500 ml
water (22 C). In a subgroup, we also tested the effect of 500 ml of 37 C
warm water. After completion of drinking, measurements were contin-
ued for another 90 min.
Microdialysis
Microdialysis studies were conducted in the supine position as de-
scribed previously (7, 8). Briefly, one (systemic
␤
-adrenoreceptor block-
ade) or two (local
␤
-adrenoreceptor blockade) microdialysis probes were
inserted into sc adipose tissue at the level of the umbilicus. BeforeAbbreviations: BMI, Body mass index; RQ, respiratory quotient.
0021-972X/03/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 88(12):6015–6019
Printed in U.S.A. Copyright © 2003 by The Endocrine Society
doi: 10.1210/jc.2003-030780
6015

insertion of the probes, the respective area was anesthetized superficially
with EMLA cream (AstraZeneca GmbH, Wedel, Germany). On the day
with systemic
␤
-adrenoreceptor blockade, the subjects ingested meto-
prolol (Stada Arzneimittel AG) before testing, and the probe was per-
fused with Ringer’s solution (Serumwerke Bernburg AG, Bernburg,
Germany) supplemented with 50 mm ethanol (B. Braun Melsungen AG,
Melsungen, Germany), for monitoring changes in blood flow, and 10
␮
m
ascorbate (Jenapharm GmbH & Co. KG, Jena, Germany). On the day
with local
␤
-adrenoreceptor blockade, the subjects ingested placebo
before testing, and the perfusate for one microdialysis probe was sup-
plemented with 100 nm of the nonselective
␤
-adrenoreceptor blocker
propranolol (Obsidan; ALPHARMA-ISIS, Langenfeld, Germany).
CMA/60 microdialysis probes and CMA/102 microdialysis pumps
(both from CMA Microdialysis AB, Solna, Sweden) were used. The flow
rate was 2
␮
l/min.
Analytical methods
Ethanol concentration was determined in the perfusate (inflow) and
dialysate (outflow) using a standard enzymatic assay (6). Dialysate
concentrations of glycerol, glucose, and lactate were determined by
standardized enzymatic colorimetric methods using the CMA/600 au-
tomatic analyzer (CMA Microdialysis AB). Plasma osmolarity was de-
termined with the freezing point depression method (Model A Osmom-
eter, Precision Scientific, Winchester, VA).
Calculations and statistics
Energy expenditure and substrate oxidation rates were calculated
according to Ferrannini (9). Changes in blood flow were determined
using the ethanol dilution technique based on Fick’s principle (9–11).
Accordingly, a decrease in the ratio between ethanol in the dialysate and
perfusate [(EtOH)
d
/(EtOH)
p
] corresponds to an increase in blood flow
and vice versa. Dialysate glycerol concentration was measured to assess
changes in lipolysis and/or lipid mobilization (12). Dialysate concen-
trations of glucose and lactate were determined to characterize glucose
supply and glycolysis, respectively. In previous studies, in situ recovery
for glycerol, glucose, and lactate in the dialysate was found to be ap-
proximately 30% using near-equilibrium dialysis at 0.3
␮
l/min (13). All
data are given as means ⫾ sem. Statistical analyses were carried out by
ANOVA with repeated measures using with
␤
-adrenoreceptor blockade
or without
␤
-adrenoreceptor blockade and time as factors to determine
the significance of differences in energy metabolism and hemodynamic
and metabolic response in adipose tissue to water in normal weight men
and women, respectively. For testing, a statistical program (InStat, Ver-
sion 3.0; Graphpad Software Inc., San Diego, CA) was used. Significant
F ratios from the ANOVA were followed by post hoc comparisons among
means using Bonferroni’s multiple t test.
Results
Energy metabolism
Resting energy expenditure was 5.06 ⫾ 0.30 kJ/min in men
and 4.02 ⫾ 0.17 kJ/min in women (P ⬍ 0.001, men vs.
women). Within 10 min after drinking water, energy expen-
diture started to increase. Sixty minutes after drinking water,
energy expenditure increased 30% in men and 30% in women
(Fig. 1A, P ⬍ 0.001). Resting RQ was 0.841 ⫾ 0.013 and
0.794 ⫾ 0.009 in men and women, respectively (Fig. 1B, P ⬍
0.01, men vs. women). In women, RQ did not change sig-
nificantly until 30 min after water drinking (Fig. 1B). After 40
min, RQ decreased significantly to a minimum of 0.75. The
sharp decrease in RQ was followed by an increase up to 0.88
between 50 and 90 min (Fig. 1B). In contrast, in men, RQ
decreased to 0.79 after 30 min and remained at that value for
the next 30 min (Fig. 1B). RQ approached the baseline value
after 90 min (Fig. 1B). Carbohydrate oxidation rate did not
change significantly in men during 90 min after water drink-
ing (Fig. 1C). In contrast, in women, carbohydrate oxidation
FIG. 1. Changes in energy expenditure
(EE), RQ, carbohydrate oxidation rate
(COX), and lipid oxidation rate (LOX)
after drinking 500 ml water (22 C). Val-
ues at t ⫽ 0 min refer to baseline (before
water drinking). Data are given as
means ⫾ SE (n ⫽ 7 for both men and
women). EE increased by about 30% in
both men and women (P ⬍ 0.001) after
water drinking. Resting RQ was signif-
icantly higher in men vs. women (P ⬍
0.05). Sixty minutes after water drink-
ing, RQ was significantly lower in men
but significantly higher in women when
compared with baseline (P ⬍ 0.05). COX
was significantly increased in women
(P ⬍ 0.001) but unchanged in men after
water drinking. In contrast, LOX was
significantly increased in men (P ⬍
0.001) but unchanged in women after
water drinking.
6016 J Clin Endocrinol Metab, December 2003, 88(12):6015–6019 Boschmann et al. • Water and Thermogenesis

increased about 2-fold (not significant) during the first 50
min after water drinking and about 3-fold (P ⬍ 0.05) during
the following 40 min after water drinking. (Fig. 1C). During
the first 40 min, the lipid oxidation rate increased in both men
(⫹100%) and women (⫹50%). During the next 30 min, the
lipid oxidation rate remained elevated in men, whereas it
declined back to baseline values in women (Fig. 1D). After 90
min, the lipid oxidation rate was still elevated in men,
whereas it decreased below baseline values in women
(Fig. 1D).
In a subset of volunteers (n ⫽ 7), the effect of systemic
␤
-adrenoreceptor blockade on the water-induced increase in
energy expenditure was tested. Again, all seven subjects
showed an increase in energy expenditure from 292 ⫾ 21 to
359 ⫾ 23 kJ/h (Fig. 2A). In six subjects,
␤
-adrenoreceptor
blockade almost completely prevented the increase in energy
expenditure after water drinking (Fig. 2B). In one woman,
energy was only slightly attenuated with
␤
-adrenoreceptor
blockade.
In another subset of volunteers (n ⫽ 4), the influence of
water temperature on the water-induced increase in energy
expenditure was tested. The water-induced change in energy
expenditure was about 70 kJ at 22 C and about 40 kJ at 37 C,
a difference of about 30 kJ between the two temperatures.
(Fig. 3). Water drinking elicited a consistent decrease in ve-
nous osmolarity. Plasma osmolarity was 296 ⫾ 1 mosmol/
liter before water drinking and 289 ⫾ 1 mosmol/liter after
water drinking (P ⬍ 0.01).
Adipose tissue metabolism
The baseline ethanol ratio was 0.39 ⫾ 0.03 and 0.29 ⫾ 0.05
(P ⬍ 0.05, men vs. women) in adipose tissue of men and
women, respectively. Water drinking did not affect the eth-
anol ratio. Additionally, the ethanol ratio remained un-
changed during both systemic and local
␤
-adrenoreceptor
blockade (data not shown). Baseline dialysate glucose was
0.76 ⫾ 0.14 and 1.02 ⫾ 0.21 mmol/liter (P ⬍ 0.05, men vs.
women) in men and women, respectively. These values did
not change significantly after water drinking in both groups,
either in the absence or in the presence of local or systemic
␤
-adrenoreceptor blockade (data not shown). Baseline dia-
lysate lactate was 0.42 ⫾ 0.12 and 0.47 ⫾ 0.08 mmol/liter in
men and women, respectively. Water drinking elicited a
significant 45% increase in dialysate lactate in men (Fig. 4).
Interestingly, that increase was almost completely prevented
by systemic but not by local
␤
-adrenoreceptor blockade (Fig.
4). In contrast, dialysate lactate did not change in women
after water drinking. However, dialysate lactate increased
50% in women in the presence of systemic but not local
␤
-adrenoreceptor blockade (Fig. 4). Baseline dialysate glyc-
erol was 58 ⫾ 15 and 96 ⫾ 16
␮
mol/liter in men and women,
respectively (P ⬍ 0.05, men vs. women). After water drink-
ing, a slight but nonsignificant increase in dialysate glycerol
(⫹20%) was noted in men, which was prevented by systemic
but not by local
␤
-adrenoreceptor blockade (Fig. 4). How-
ever, in women, no changes in dialysate glycerol were ob-
served (Fig. 4).
Discussion
The novel finding in this study is that drinking 500 ml of
water increases metabolic rate by 30% in both men and in
women. The increase in metabolic rate was observed within
10 min after completion and reached a maximum 30–40 min
after water drinking. The effect was sustained for more than
an hour. The cardiovascular changes after water drinking
that we described earlier exhibited a similar time course (1–3,
10–12). Based on our measurements, we estimate that in-
creasing water ingestion by 1.5 liters would augment daily
energy expenditure by approximately 200 kJ. Over 1 yr,
energy expenditure would increase by 73,000 kJ (17,400 kcal),
the energy content of 2.4 kg adipose tissue. By comparison,
ingestion of 50 mg of ephedrine thrice daily increases energy
expenditure by approximately 320 kJ/d (13). The substrates
that fueled the increase in metabolic rate differed between
men and women. In men, water drinking led to a marked
increase in lipid oxidation. Carbohydrate oxidation did not
change after water drinking. In contrast, in women, carbo-
hydrates mainly fueled the increase in metabolic rate after
water drinking.
Our data strongly suggest that the increase in metabolic
rate with water is related to sympathetic activation and in-
creased stimulation of
␤
-adrenergic receptors. Indeed, the
maximal increase in metabolic rate after water drinking cor-
responds to the maximal sympathetic activation in previous
studies (2, 3). Systemic
␤
-adrenoreceptor blockade substan-
tially attenuated the water-induced increase in metabolic
rate. Based on this observation, one might speculate that
water drinking during
␤
-adrenoreceptor blockade may re-
duce body temperature. Unfortunately, we did not deter-
mine body temperature. We propose that limb vasoconstric-
FIG. 2. Changes in energy expenditure (EE) after drinking 500 ml
water (22 C) alone (A) or with systemic
␤
-adrenergic blockade by
metoprolol (B). Cumulative values over 1 h are given. Data are given
as means ⫾ SE.*,P ⬍ 0.05 when compared with baseline (rest).
FIG. 3. Effect of water temperature (22 C or 37 C) on changes in energy
expenditure after drinking of 500 ml water. Cumulative values over 1 h
are given. Data are given as means ⫾ SE.*,P ⬍ 0.05, 22 C vs. 37 C.
Boschmann et al. • Water and Thermogenesis J Clin Endocrinol Metab, December 2003, 88(12):6015–6019 6017

tion after water drinking (3) may be sufficient to maintain
thermal homeostasis even in the absence of an increase in
metabolic rate.
We used the microdialysis technique to monitor metabolic
changes, both systemically and at the tissue level. Water
drinking did not change adipose tissue blood flow as deter-
mined by the ethanol dilution technique (7, 8, 14, 15). There-
fore, changes in metabolite concentrations after water drink-
ing cannot be explained by local blood flow changes. We
were particularly interested to learn whether or not the ox-
idized lipids were derived from sc stores. In men, interstitial
glycerol increased substantially after water drinking. The
response was abolished by systemic but not local
␤
-adreno-
receptor blockade. Thus, in men, water drinking increases
lipid mobilization through stimulation of
␤
-adrenoreceptors.
However, the lipids are not derived from sc abdominal ad-
ipose tissue. In women, dialysate glycerol did not change
after water drinking regardless of the presence or absence of
␤
-adrenoreceptor blockade.
Dialysate glucose concentrations did not change after wa-
ter drinking. This observation suggests that the balance be-
tween glucose supply and glucose utilization in adipose tis-
sue did not change with water. In men, dialysate lactate
increased even though systemic carbohydrate oxidation was
not increased. The increase in lactate is consistent with in-
creased glycolysis. The effect was suppressed by systemic
but not local
␤
-adrenoreceptor blockade. Thus, the lactate is
not generated in sc adipose tissue. We speculate that the
increase in lactate production may result from an increase in
glucose release from the liver that is suppressed with
␤
-
adrenoreceptor blockade. In women, dialysate lactate was
not increased. Presumably, glucose was more completely
oxidized in women, as evidenced by the increase in carbo-
hydrate oxidation. Paradoxically, dialysate lactate increased
after water drinking during systemic but not local
␤
-adre-
noreceptor blockade. Perhaps a decrease in lipid mobiliza-
tion and oxidation was followed by an increase in glycolysis.
The gender-specific effect of water might be related to dif-
ferences in body composition or hormonal factors (16).
The mechanism that elicits sympathetic activation with
water drinking remains unclear (17). The pressor response
does not seem to be influenced by water temperature (2). Part
of the increase in energy expenditure may have been due to
the energy required to heat the water from room temperature
to body temperature (500 ml ⫻ 15 C ⫽ 7500 cal ⫽ 30 kJ). The
calculated energy expenditure attributed to heating the wa-
ter closely matched the difference between the thermogenic
effect of 22 C water and 37 C water in our metabolic chamber
studies. Thus, approximately 60–70% of the water-induced
thermogenesis cannot be attributed to the heating of the
ingested water. Gastric distension increases sympathetic ac-
tivity in humans (18). However, at the time of the maximal
response, less than 125 ml water remain in the stomach (19).
We observed a mild but nevertheless consistent reduction in
plasma osmolarity after water drinking, which mirrored the
time course of the metabolic response. In humans, infusion
of hypo-osmolar solutions through a gastric tube causes a
greater increase of sweat production, a sympathetic re-
sponse, than infusion of isosmolar solutions (20). Perhaps the
sympathetic activation with water drinking involves osmo-
receptive or sodium-sensitive afferent nerve fibers (21, 22).
One important implication of our study is that the effect of
FIG. 4. Relative changes in dialysate
lactate and glycerol in adipose tissue in
men (n ⫽ 7) and in women (n ⫽ 7) after
drinking 500 ml water (22 C). CTRL,
Control, Ringer’s solution only; BBL, lo-
cal
␤
-adrenergic blockade by 100 nM
propranolol added to the perfusion
medium; BBS, systemic
␤
-adrenergic
blockade by ingestion of 100 mg meto-
prolol. Data are given as means ⫾ SE.In
men, dialysate lactate increased signif-
icantly (P ⬍ 0.01) after water drinking,
and this effect was prevented by sys-
temic but not local
␤
-adrenergic block-
ade. In contrast, in women, dialysate
lactate did not change significantly af-
ter water drinking alone but increased
significantly (P ⬍ 0.05) in the presence
of systemic
␤
-adrenergic blockade. Di-
alysate glycerol increased slightly but
nonsignificantly in men. However, that
increase was not observed during
␤
-
adrenergic blockade. In women, no
changes at all were observed in dialy-
sate glycerol with any protocol used.
6018 J Clin Endocrinol Metab, December 2003, 88(12):6015–6019 Boschmann et al. • Water and Thermogenesis

water on energy expenditure and fuel utilization should be
recognized as a powerful confounding factor in metabolic
studies. Indeed, water drinking-induced thermogenesis is an
important and unrecognized component of daily energy ex-
penditure. If confirmed in other studies, this cost-free inter-
vention may be a useful adjunctive treatment in overweight
and obese individuals to attain an increase in energy
expenditure.
Acknowledgments
Received May 5, 2003. Accepted August 14, 2003.
Address all correspondence and requests for reprints to: Jens Jordan,
M.D., Clinical Research Center, Wiltbergstrasse 50, D-13125 Berlin, Ger-
many. E-mail: jordan@fvk-berlin.de.
This work was supported in part by the Deutsche Forschungsge-
meinschaft. J.J. is a recipient of a Helmholtz fellowship of the Max-
Delbrueck-Center of Molecular Medicine.
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