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Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr 49, 44-50


Abstract and Figures

Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3-4% (p less than 0.02) over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects. Measurements of energy expenditure (EE) in a room respirometer indicate that repeated caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the EE of both subject groups by 8-11% (p less than 0.01) during that period but had no influence on the subsequent 12-h night EE. The net effect was a significant increase (p less than 0.02) in daily EE of 150 kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity.
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Normal caffeine consumption: influence on thermogenesis
44 Am i C/in Nuir l989;49:44-S0. Printed in USA. C 1989 American Society for Clinical Nutrition
and daily energy expenditure in lean and postobese
human volunteers14
AG Duioo, CA Geissler, THorton, A Collins, and DSMiller
ABSTRACT Single-dose oral administration of 100 mg caffeine increased the resting met-
abolic rate of both lean and postobese human volunteers by 3-4% (p < 0.02) over 150 mm
and improved the defective diet-induced thermogenesis observed in the postobese subjects.
Measurements of energy expenditure (EE) in a room respirometer indicate that repeated
caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the EE of
both subject groups by 8-1 1% (p < 0.01) during that period but had no influence on the subse-
quent 12-h night EE. The net effect was a significant increase (p < 0.02) in daily EE of 150
kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly con-
sumed doses can have a significant influence on energy balance and may promote thermogene-
sis in the treatment ofobesity. Am JC/in Nutr 1989;49:44-50.
KEY WORDS Obesity, thermogenesis, caffeine, energy expenditure
The widespread use ofcaffeine in drinks, food, and nu-
merous pharmaceutical preparations, such as muscle re-
laxants, decongestants, and allergy drugs, has generated
much interest in elucidating the multitude ofeffects and
mechanisms ofaction ofthis drug ofeveryday life. With
increasing evidence pointing to a thermogenic defect as
being contributory to the etiology of obesity (1), nutri-
tionists are particularly interested in caffeine’s effects on
energy expenditure (EE), not only as an apparently safe
thermogenic drug but also as a pharmacological tool to
elucidate the mechanisms of thermogenesis and meta-
bolic differences between lean and obese people.
Although the stimulatory effect of caffeine on meta-
bolic rate in man is well established and was demon-
strated both in subjects who fasted (2-7) and in those
who did not (5, 6), most of these studies focused on
caffeine’s acute thermogenic effects when administered
at relatively large doses. There is little information about
caffeine’s influence on daily EE and the thermogenic
effects of caffeine in amounts that are generally con-
sumed at any one time (as in a cup ofcoffee or in prepara-
tions usually containing 100 mg caffeine).
We conducted studies in lean and postobese human
volunteers that examined the effect of commonly con-
sumed doses of caffeine on the resting metabolic rate
(RMR), diet-induced thermogenesis, and 24-h energy
Eighteen healthy volunteers were selected from students and
staff of King’s College, London University and were allocated
to two groups by the ease with which they maintained a rela-
tively lean body weight. One group (lean group; n=9, six fe-
males, 3 males) consisted oflean subjects who claimed to main-
thin body weight without effort. The other group (postobese
group; n=9, six females, three males) comprised subjects who
admitted to a weight problem and were previously overweight
with grade I (mild to moderate) obesity; their Quetelet index
(wt/ht2) ranged from 26.1 to 29.6 with a mean value of 27.3
±0.5 SEM. The various grades ofobesity based on the Quetelet
Index (or body mass index) were described by Garrow (8).
These obese subjects can only maintain a normal body weight
by restricting their food intake, otherwise they would become
overweight again within a few months. Although they are pre-
disposed to obesity, they had maintained a normal body weight
for at least 5-6 mo before the study began.
IFrom the Department of Nutrition, King’s College, University of
London, UK, and the Department of Medicine, Harvard Medical
School, Boston, MA.
2DS Miller is deceased.
3Supported in part by a grant from the International Foundation
for the Promotion ofNutrition Research, ISFE, Zurich (AGD); a grant
from King’s College (MC); and a grant from the Ashdown Trust (TH).
4Address reprint requests to AG Dulloo, Centre Medicale Universi-
taire, Department ofPhysiology, University ofGeneva, 9 av de Cham-
pel, CH-l21 1 Geneva 4, Switzerland.
ReceivedJuly9, 1987.
Accepted for publication January 5, 1988.
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At the outset ofthe study, body weight and height were mea-
sured in both subject groups and the degree of obesity (if any)
was reevaluated by using the Queletet index and by estimating
the percentage body fat. Percentage body fat was assessed by
the method ofDurnin and Womersley (9) from measurements
ofskinfold thicknesses with a Harpenden skinfold caliper (Hot-
tam Ltd, Dyfed, Wales, UK). Lean body mass was calculated
by subtracting body fat from body weight. Food was weighed
and intake was recorded for 7 d immediately before the study;
energy content was expressed as daily means. Analysis of nutri-
ent composition showed no difference between the two groups
in the proportion of metabolizable energy intake (1 ±SEM)
derived from protein (lean subjects, 17 ±1%; postobese sub-
jects, 16 ±1%), fat (lean subjects, 32 ± 3%; postobese subjects,
34 ± 2%), and carbohydrate (lean subjects, 5 1 ± 2%; postobese
subjects, 50 ± 2%). Methylxanthine intake (eg, caffeine, the-
ophylline) from beverages (coffee, tea, hot chocolate, and coke)
ranged from 250 to 500 mg/d. All subjects were thus classified
as mild to moderate consumers of methylxanthines. None of
the subjects had a familial history ofdiabetes and none engaged
in physical training, regular exercise, or sport activities.
The study was carried out in accordance with the regulations
of the Ethical Committee for Human Experimentation of
King’s College, University of London.
Acute metabolic-rate studies
The subjects’ metabolic rate while fasting and not fasting was
measured by open-circuit indirect calorimetry using 100 L ca-
pacity Douglas bags and mouthpiece connections with respira-
tory valves. Details ofthese measurements were described pre-
viously (10) and involved measurements of oxygen consump-
tion rates and calculations of heat production using the Weir
formula(l 1).
All subjects were given four randomized treatments on four
different days and with at least a 2.4 interval between treat-
ments. The four treatments were 1) a 100-mg tablet of anhy-
drous caffeine (Pro-plus, Boots Ltd. Nottingham, UK); 2) a
300-kcal liquid meal(Complan#{174}, Glaxo, Devon, UK) made up
to 200 mL with water; 3) a 300-kcai liquid meal plus a 100-mg
tablet ofcaffeine; and 4) a 200-mL glass ofH2O. The complan
powder contained (per/kg) 180 g protein, 470 g carbohydrate,
and 330 g fat with an energy value of4.4 kcal/g dry wt.
The subjects arrived at the university department at 0800
after an overnight 12-h fast. They had traveled either by auto-
mobile or by public transportation. They were requested to
walk casually, to use elevators rather than stairs, and to avoid
any burst ofphysical activity on the way to the laboratory. On
arrival a subject was seated in a comfortable armchair and
spent the duration ofthis acute study either reading or relaxing.
The pretreatment phase consisted of at least 30 mm of relax-
ation followed by three or four measurements of base-line
RMR, each lasting 5 mm with a 5-10 mm interval between
measurements. After each treatment was administered, mea-
surements of metabolic rate were performed over the next 150
mm, each lasting 5mm with intervals of 10-15 mm between
To ensure steady-state breathing the subjects breathed for a
few minutes through the mouth piece and tubing system with
the tap for expired air closed to the Douglas bag but open to
ambient air. The tap to the bag was then opened and expired
air was collected for the next 5 mm. All subjects were familiar
with this technique for measuring metabolic rate and felt no
discomfort during the study.
Daily energy expenditure
Five lean (three females, two males) and six postobese (three
females, three males) subjects participated in this study. EE was
measured for 24 h in a human respirometer ( 10) on two sepa-
rate occasions for each subject. One measurement determined
base-line (control) EE in the absence of any methylxanthine
and the other measurement determined EE during the admin-
istration of caffeine. At least a l-wk interval was allowed be-
tween these 2 d of measurements, which were carried out in a
randomized order for all subjects. All subjects were requested
to ensure that their activity and food consumption patterns
were normal (with no unusual excesses in either direction) for
at least 2 d before the measurements were taken.
On each measurement day the subject reported to the labo-
ratory between 0800 and 0830 after an overnight fast. After at
least 30 mm of rest and relaxation in a comfortable armchair,
the subject entered the respirometer at 0900 and left at 0900
the next day. While inside the respirometer, the subject spent
time reading, studying, lying in bed, listening to the radio, or
watching television. The subject kept an activity diary (dura-
tion to the nearest minute) describing position and activity
throughout the 24 h. No methylxanthine-containing food or
beverages were provided on either day, but subjects were pro-
vided with meals and drinks with an energy content similar to
their mean customary energy intakes. On the treatment day
each subject ingested six caffeine tablets (100 mg/tablet), one
tablet every 2 h for 12 h as follows: 0900 with breakfast, 1 100,
1300 with lunch, 1500, 1700, and 1900 with dinner.
Data were analyzed by Student’s ttest and by two-way analy-
sis ofvariance with repeated measures. Posthoc comparison be-
tween pairs of treatments were performed with the Newman-
Keul’s multiple sample comparison test after analysis of vari-
ance had established significant differences between treatments
(12). All results are presented as mean ±SEM.
The physical characteristics of the subjects are out-
lined in Table 1 .Height was similar in both groups but
the mean value for body weight was ‘--9% higher in post-
obese subjects than in lean subjects; this difference was
not statistically significant. The mean value for age was
also slightly higher (NS) in the postobese group (range
20-46 y) than in the lean group (range 1 8-35 y). The
Quetelet Index, ranging from 18.5 to 23.4 in the lean
group and from 19.5 to 24.9 in the postobese group, mdi-
cates that none ofthe subjects could be classified as obese
at the start ofthe study. The percentage body fat was sim-
ilar in both groups whereas lean body mass was 8%
higher (NS) in the postobese group. Food intake, mea-
sured for 1 wk, was significantly lower in the postobese
group than in the lean group by ‘-.-25% in absolute terms
(p < 0.0 1) and by 30% per kilogram body weight (p
<0.001). The postobese group maintained their weight
on a mean energy intake of 1600 kcal, which was 500
kcal less than that ofthe lean group.
Acute metabolic-rate studies
Table 1 shows the pretreatment RMR computed over
the measurement days after an overnight 12-h fast. The
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Physical characteristics, customary food intake, and pretreatment resting metabolic rate (RMR) ofsubject groups
Age Height Body
weight Body fat Quetelet
intake by
weight Pretreatment
ycm kg % kg/cm kg kcal/d’ .d kcal/min .d
Leansubjects 24.8± 1.6 169±3 58.3±3.1 22.1 ±2.6 20.6±0.5 45.8±3.8 2105± 117 37.5±2.4 1.046±0.069 25.8±0.96
Postobesesubjects 28.2±2.6 168±2 63.5±3.1 21.9± 1.3 22.2±0.7 49.5±3.1 1592± 91 25.6± 1.4 1.036±0.039 23.6±0.7
*I±SEM, n=9per group; six females, three males per group.
within-subject coefficient of variation (1 ±SD) during
the measurement days ranged from 1.4 ± 1 .0 to 2.7
±1.5% in the lean group and from 1.6 ± 1 .3 to 1.8
±1.4% in the postobese group. The between-day coeffi-
cient of variation (1 ± SD) was 2.4 ± 2.5% in the lean
group and 2.6 ± 2. 1% in the postobese group. The RMR
in absolute terms was not different between the two sub-
ject groups but when the data were expressed per unit
body weight to account for both between-group as well
as within-group variations in body weight, RMR was 8%
lower in the postobese group than in the lean group. This
difference nearly achieved statistical significance (p
=0.056). Similarly, the RMR per unit lean body mass
was 8% lower (p =0.06) in the postobese group than in
the lean group.
The values for metabolic rate before and after treat-
ment are shown in Table 2 and the data for the total ther-
mogenic response (both absolute and percentage in-
creases) over the 150-mm posttreatment period are pre-
sented in Table 3. The thermogenic response curves,
expressed as a percentage ofthe base-line (pretreatment)
RMR, are shown in Figure 1 for both lean and postobese
groups. The control water treatment had no effect on the
RMR of either group (Fig 1). In contrast, ingestion of
100 mg caffeine with a similar volume ofH2O increased
metabolic rate in both groups. Metabolic rates reached
peak values within 20 to 40 mm after treatment and de-
creased gradually toward base-line levels. At the end of
the study, the metabolic rate in both groups was not sig-
nificantly different from base-line values.
The thermogenic response curve followed a similar
pattern in both the lean and the postobese subjects, and
the total thermogenic response integrated over the entire
150-mm study period (Table 3) was increased by 3-4%
in both subject groups. This posttreatment increase in
metabolic rate was statistically significant when com-
pared with either the corresponding pretreatment RMR
or the posttreatment RMR assessed during the con-
trol day.
Ingestion ofa 300 kcal liquid meal caused a sharp rise
in metabolic rate that reached peak levels in 30-60 mm
in both subject groups. The peak increase in metabolic
rate was significantly greater (p <0.001) in lean subjects
(+25%) than in postobese subjects (+ 15%). Both groups
maintained peak metabolic rate for about another hour,
after which the metabolic rate declined at a faster rate in
the postobese group than in the lean group. At the end
ofthe 1 50 mm, the metabolic rate ofthe lean group was
still ‘ 17% above base-line RMR (p <0.001) whereas
that ofthe postobese group was only 5% higher (NS). As
shown in Tables 2 and 3, the overall thermogenic re-
sponse ofthe postobese subjects to the 300 kcal meal was
only halfofthat measured in the lean subjects.
Administration ofa 100-mg caffeine tablet in the lean
group produced a small additional (+ 12%, NS) stimula-
tory effect on their thermogenic response to food. In the
postobese group, caffeine was more effective in augment-
ing the thermogenic effect of the meal; both the peak
metabolic rate and the total thermogenic response (inte-
grated over 150 mm) were 25-30% higher after caffeine
and a meal than after the meal alone. The 50% reduction
in diet-induced thermogenesis (DIT) observed in the
Metabolic rate before and after treatment with 100 mg caffeine a nd/or a 300-kcal liquid meal in lean and po stobese subjects*
Caffeine Meal Meal +caffeine
Before After Before After Before After
Lean subjects
Postobese subjects 1.055 ±0.07 1 1.095 ±0.063t
I .026 ±0.043 1.059 ±0.045 I .025 ±0.064 1.236 ±0.077j
I.039 ±0.038 1.164 ±0.052t 1.055 ±0.075
I.047 ±0.034 1.292 ±0.087f
1.2 13 ±0.04Sf
*j: SEM, n=9 per group; six females, three males per group.
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4_9 -12h)   9am..,
0 30 60 90 20 50
Lean Post-
Increases in metabolic rate over 150 mm in response to 100 mg caffeine and/or a 300-kcal liquid meal in lean and postobese subjects
Absol ute increase Perce ntage increase
Meal Meal
+caffeine Posthoc +caffeine Posthoc
Caffeine [1] Meal [2] [3] comparison Caffe inc [1] Meal [2] [31 comparison
kcal/min %
Leansubjects 0.040±0.016 0.210±0.015 0.236±0.014 1 vs2,3p<0.001 4.38± 1.8 20.6±0.9 22.7± 1.1 1 vs2,3p<0.OOl
2vs3 NS 2vs3 NS
Postobese 0.032±0.009 0.125±0.018 0.165 ±0.015 1 vs2,3p<0.OOl 3.16±0.87 11.8± 1.4 15.7± 1.3 1 vs2,3p<0.OOl
Significance o fFbetween treatments
between groups
2 vs 3 p <0.05
p<0.001 Significance ofFbetween treatments
between groups
2 vs 3 p <0.05
p <0.001
*SEM, n=9 per groups; six females, three males per group.
postobese group was ameliorated to an extent that their
thermogenic response to food with caffeine was only 25%
below that of the lean group. Thus the subnormal DIT
ofthe postobese group was partially corrected by the ad-
ministration of caffeine. However, the thermogenic re-
sponses in both subject groups after a meal were not mea-
sured until the study ended and were thus underesti-
Daily energy expenditure
The data on 24-h EE measured in the respirometer
were divided into two 12-h periods (Fig 2, Tables 4 and
5): the 12-h day period (0- 12 h EE) during which the
caffeine tablets were administered, followed by a second
Minutes after Treatment
FIG 1.Thermogenic response of lean and postobese subjects to a
100-mg caffeine tablet administered after fasting, to a 300 kcal mixed
meal, or to a combination of caffeine and a meal. The effect of the
control water load is also shown for the lean (closed circles) and for the
postobese subjects (open circles). Vertical bars represent the SEM
12-h night period (12-24 h EE) when no caffeine was
ingested. The mean EE (MJ/person) was 8-10% lower in
the postobese group than in the lean group (Fig 2) but
these differences were not statistically significant. How-
ever, analysis ofvariance (Table 4) shows that during the
control study and also during treatment with caffeine,
EE expressed per unit body weight was significantly
lower by 13-18% in the postobese group than in the lean
group for 0- 12-h EE, 1 2-24-h EE, and total 24-h EE.
Administration of caffeine increased the 0-12-h EE in
Post -
FIG 2. Energy expenditure compartmented into the first 12-h d pe-
riod (0.-I 2 h) and the subsequent 12-h night period (12-24 h) in lean
(n =5) and postobese (n =6) subjects during a control study (open
bars) and during administration ofcaffeine. Vertical bars represent the
SEM values. The probability level for significant differences is for
paired data. MJ values can be converted to kcal by multiplying them
by 239.
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Energy expenditure (kcal/kg) in respirometer during base-line (control) study and during treatment with caffeine
0-12h l2-24h 0-24h
Control Caffeine Control Caffeine Control Caffeine
Lean subjectst 17.2 ±0.8 19.2 ±0.9 13.4 ±0.6 13.2 ±0.4 30.6 ±0.9 32.3 ±0.9
Postobesesuhjectsf 14.5 ±0.8 15.7 ±0.8 1 1.3 ±0.4 11.5 ±0.5 25.8 ±0.9 27.2 ±1.2
Significance ofF
between treatments p <0.01 NS p <0.01
between groups p <0.025 p <0.02 p <0.01
tn=5; three females, two males.
1:n=6; three females, three males.
the lean and postobese groups to a similar extent but had a demonstrable stimulatory effect on RMR. In addition,
no significant effect on the subsequent 12-24-h EE in ci- it seems that the thermogenic effect ofcaffeine in man is
ther subject group (Fig 2, Table 5). Thus, the total 24-h dose dependent because the present data and the results
EE was significantly increased in both groups. ofother studies (2-7, 14) indicate that the magnitude of
The data on activity levels measured within the respi- response increases almost linearly with higher doses:
rometer were analyzed by computing the amount oftime over 2-2.5 h the thermogenic responses to doses of 100,
spent on various activities. Activities were categorized as 200-250, and 400-450 mg were 4-5, 10-12, and 16%,
sleeping, lying, sitting quietly (ie, minimal action, such respectively.
as reading, watching television, etc), sitting actively (eg, The current data also indicate that after fasting both
eating, writing, knitting, etc), and pottering or fidgeting the lean and the postobese subjects show similar in-
(eg, moving around the room to collect meals, perform- creases in metabolic rate after caffeine is ingested. These
ing personal toilets, etc). In the respirometer there were findings are compatible with a previous study (6) in
no differences in activity patterns between subject groups which no difference was observed between lean and
or between treatments. obese groups but are in direct conflict with another re-
port (7) in which the thermogenic response of the post-
Discussion obese subjects to caffeine is one-third less than that in
lean subjects. These discrepancies could be because in
Effect ofcaffeine on resting metabolic rate and the latter study (7) both groups received the same
diet-induced thermogenesis amount of caffeine even though the postobese subjects
This study demonstrates that caffeine increased the weighed about one-third more than the lean subjects and
RMR by 3-4% over 2.5 h at doses as low as 100 mg. therefore received a smaller dose of caffeine per unit
Because early studies (1 3, 14) indicated that RMR was body weight. This explanation is supported by data from
unaltered by lower doses of caffeine, it is likely that the the same study that indicated a lower plasma caffeine
amount ofcaffeine administered in our study represents level in postobese subjects than in lean subjects. In the
the minimum (or near minimum) dose that would allow present study the mean body weight and lean body mass
Changes in energy expenditure measured in a respirometer during administration of caffeine*
Absolute changes Percentage changes
0- 12 h 12-24 h 0-24 h 0-1 2 h 12-24 h 0-24 h
Leansubjectst 120±36 -11±25 109±50 11.4±3.1 -1.8±3.3 5.5±2.3
Postobesesubjectsf 74±31 6±24 78±34 7.9±3.4 1.5±3.5 4.9± 1.8
Significance ofF
1*twetn treatments p <0.01 NS p <0.02 p <0.01 NS p <0.02
between groups NS NS NS NS NS NS
tn=5; three females, two males.
j: n =6; three females, three males.
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of the postobese group and the lean group did not differ
significantly and a similar increase in RMR resulted
from the administration ofthe same dose ofcaffeine; this
suggests that under fasting conditions both groups show
similar sensitivity in thermogenic response to caffeine.
In contrast, the thermogenic response to a mixed meal
differed considerably between the two subject groups.
The response of the postobese group was only half as
much as that of the lean group. These findings provide
further evidence for a subnormal thermogenic response
to food in those with a predisposition to obesity. Their
defective DIT was improved by caffeine, its thermogenic
effect being additive to that of the food. However,
caffeine produced only a small additional stimulatory
effect on DIT in the lean group. This apparently greater
thermogenic response in the postobese group, at least at
this relatively low dose, suggests that the postobese group
is more sensitive to caffeine than the lean group but only
when caffeine is taken with food. Similar greater thermo-
genic responses of postobese subjects than the lean sub-
jects in the fed state were reported during single-dose ad-
ministration of a sympathomimetic mixture of ephe-
drine and methylxanthines, although both groups also
showed identical thermogenic responses to the drugs in
the fasted state (10).
Influence ofcaffeine on daily energy expenditure
Although this study focuses primarily on the thermo-
genic responses oflean and postobese subjects to caffeine
rather than on a comparison oftheir absolute metabolic
rates, it nevertheless demonstrates that in addition to a
subnormal DIT the RMR and 24-h EE ofthe postobese
group were lower than in the lean group. These differ-
ences are statistically significant when the metabolic-rate
data are corrected for intergroup and intragroup varia-
tions in body weight. Similar differences (p <0.02) are
also apparent if the data are expressed per lean body
mass. Therefore, these findings support previous reports
(15-17) that postobese subjects tend to have a lower en-
ergy requirement for weight maintenance than do lean
Repeated administration of caffeine increased the EE
ofboth subject groups but only during the period of drug
administration (ie, the first 12-h day period). The lack of
any residual thermogenic effect in the second 12-h night
period is probably because any residual plasma caffeine
level would have been cleared given its relatively short
half-life of 3-3.5 h. However, the similar increase in 0-
12-h EE in both subject groups contrasts with the find-
ings ofthe single-dose study indicating that caffeine had a
much smaller stimulatory effect on DIT in the lean group
than in the postobese group. There are two explanations
for this apparent discrepancy. It is possible that after re-
peated caffeine intake the additive effect of caffeine and
food on thermogenesis in the postobese group was not
sustained and that the increase in 0-12-h EE resulted
mostly from the stimulatory effect of caffeine on the
other components of EE. Alternatively, it is plausible to
suggest that repeated administration of caffeine, result-
ing in a higher plasma level ofcaffeine than that achieved
with a single dose, stimulated DIT to a similar extent in
both the postobese group and the lean group. This agrees
with previous studies in lean subjects (5, 6) indicating
that administration ofhigher doses ofcaffeine produced
an effect additive to that of food on thermogenesis.
Therefore, the current findings and previous studies
(5, 6) imply that people with a predisposition to obesity
may differ from lean people in sensitivity but not in ca-
pacity to the stimulatory effect ofcaffeine on DIT and on
daily EE.
Cqine and weight control
A main implication of this study concerns the poten-
tial use of caffeine as an apparently safe thermogenic
agent for weight control. The effect of caffeine on appe-
tite is unknown in man, but if it is assumed that there is
no compensatory increase in food intake, the increase of
,, 5% in 24-h EE after caffeine would represent an energy
deficit of75-l 10 kcal/d. These changes may be small but
over several months could accumulate and lead to sub-
stantial changes in body weight. A long-term human
study ofthe effects ofcaffeine on body fat content is long
overdue but studies in animals demonstrated that
caffeine and other methylxanthines, albeit at high doses,
reduced body weight and body fat by both anorectic and
thermogenic effects (18). Although caffeine and other
methylxanthines were ineffective in altering EE when ad-
ministered at low doses, they can markedly potentiate
the thermogenic effects of ephedrine (a sympathomi-
metic agent) and lead to a reversal or prevention of obe-
sity in some animal models (19-2 1). In man, administra-
tion ofmethylxanthines in doses (80 mg) similar to those
administered in this study (100 mg) doubles the thermo-
genic effect of ephedrine, and such mixtures completely
normalize the defective DIT found in postobese subjects
to those levels found in lean subjects (10). The ability
ofcommonly consumed amounts ofcaffeine to increase
daily EE, as demonstrated in the present investigation,
coupled with caffeine’s ability to augment the thermo-
genic effects of certain sympathetic stimulants (10, 19-
22) may have contributed to reported weight losses in
obese humans (23). The potential use ofcaffeine as a pro-
moter of thermogenesis during the treatment of obesity
warrants further study. CI
We thank all the volunteers who participated in this study.
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... Caffeine has thermogenic effects [4][5][6][7][8][9] and has been implicated in reducing weight, body mass index (BMI), and fat mass in short term randomised controlled trials. [10][11][12] Hence, a high caffeine intake might lower the risk of diseases related to adiposity, such as type 2 diabetes and cardiovascular disease. ...
... [42][43][44] The effect of caffeine on energy expenditure is dose-dependent and the thermogenic response is positively correlated with the response in plasma caffeine. 9 A daily intake of 100 mg of caffeine has been estimated to increase energy expenditure by approximately 100 kcal (418.4 kJ) per day, 8 which could consequently lower the risk of developing obesity. The elevated energy expenditure attributable to caffeine consumption might be mediated through increased thermogenesis of brown adipose tissue. ...
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Objective To investigate the potential causal effects of long term plasma caffeine concentrations on adiposity, type 2 diabetes, and major cardiovascular diseases. Design Two sample mendelian randomisation study. Setting Genome-wide association study summary data for associations of two single nucleotide polymorphisms associated with plasma caffeine at the genome-wide significance threshold (rs2472297 near the CYP1A2 gene and rs4410790 near the AHR gene) and their association with the outcomes. Participants Primarily individuals of European ancestry participating in cohorts contributing to genome-wide association study consortia. Main outcome measures Outcomes studied were body mass index, whole body fat mass, whole body fat-free mass, type 2 diabetes, ischaemic heart disease, atrial fibrillation, heart failure, and stroke. Results Higher genetically predicted plasma caffeine concentrations were associated with lower body mass index (beta −0.08 standard deviation (SD) (95% confidence interval −0.10 to −0.06), where 1 SD equals about 4.8 kg/m ² in body mass index, for every standard deviation increase in plasma caffeine) and whole body fat mass (beta −0.06 SD (−0.08 to −0.04), 1 SD equals about 9.5 kg; P<0.001) but not fat-free mass (beta −0.01 SD (−0.02 to −0.00), 1 SD equals about 11.5 kg; P=0.17). Higher genetically predicted plasma caffeine concentrations were associated with a lower risk of type 2 diabetes in two consortia (FinnGen and DIAMANTE), with a combined odds ratio of 0.81 ((95% confidence interval 0.74 to 0.89); P<0.001). Approximately half (43%; 95% confidence interval 30% to 61%) of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index reduction. No strong associations were reported between genetically predicted plasma caffeine concentrations and a risk of any of the studied cardiovascular diseases. Conclusions Higher plasma caffeine concentrations might reduce adiposity and risk of type 2 diabetes. Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.
... The ability of caffeine to stimulate SNS activity, and thus, thermogenesis, is due to its ability to inhibit PDE and allow the accumulation of cAMP, as well as induce an increase in lipolysis, which makes caffeine a primary ingredient in many thermogenic supplements. Caffeine alone has been shown to increase metabolic rate in trained and untrained males and females at various moderate doses [13][14][15][16][17][18][19][20]. Similar to the findings of the present study, multiple studies have demonstrated that metabolic rate was moderately increased in both normal weight [13,14,19] and clinically obese [14,20] women for a short period. ...
... Caffeine alone has been shown to increase metabolic rate in trained and untrained males and females at various moderate doses [13][14][15][16][17][18][19][20]. Similar to the findings of the present study, multiple studies have demonstrated that metabolic rate was moderately increased in both normal weight [13,14,19] and clinically obese [14,20] women for a short period. The 150 mg dose in the present study was smaller than the aforementioned experiments. ...
Background Thermogenic supplements are widely used in the general population to support attempted fat loss; however, the efficacy and safety of these supplements are questioned. Purpose To determine whether a thermogenic supplement affects metabolic rate, hemodynamic responses, and mood states. Methods In a randomized double-blind crossover design, 23 females (22.2 ± 3.5 years; 164.8 ± 6.4 cm; 73.5 ± 6.9 kg) who were moderate caffeine consumers (<150 mg/day) reported to the lab after a 12 h fast for baseline assessments of resting energy expenditure (REE) via indirect calorimetry, heart rate (HR), blood pressure (SBP and DBP), blood variables, and hunger, satiety, and mood states. Thereafter, subjects ingested the assigned treatment (active treatment containing caffeine, micronutrients, and phytochemicals [TR] or placebo [PL]). All variables were reassessed at 30-, 60-, 120-, and 180 min post-ingestion. Subjects repeated the same protocol with ingestion of the opposite treatment on a separate day. All data were analyzed using a 2 × 5 ANOVA with repeated measures and significance was accepted a priori at p < 0.05. Results In the TR group, mean increases in REE of 121 to 166 kcal/d were observed at 30-, 60-, and 180 min post-ingestion (p < 0.01 for all). PL group mean decreases in REE of 72 to 91 kcal/day were observed at 60-, 120-, and 180 min (p < 0.05 for all). Respiratory quotient decreased at 120 and 180 min in both treatments. Slight increases in SBP of 3–4 mmHg were observed at 30, 120, and 180 min (p < 0.05 for all) post-ingestion of TR, while no effects were observed for DBP. Observed increases in SBP were within normal blood pressure ranges. TR decreased subjective fatigue with no other significant changes in mood states. Glycerol was maintained in TR, while there was a decrease at 30, 60, and 180 min (p < 0.05 for all) post-ingestion of PLA. Free fatty acids increased in TR at 60 and 180 min (p < 0.05) post-ingestion as well as a significant difference between treatments at 30 min post-ingestion indicating greater circulating free fatty acids levels in TR vs. PL (p < 0.01). Conclusion These findings indicate that ingestion of a specific thermogenic supplement formulation produces a sustained increase in metabolic rate and caloric expenditure and reduces fatigue over 3 h without producing adverse hemodynamic responses.
... Its administration can lead to Frontiers in Pharmacology (Dulloo et al., 1989) -Thermogenic agent (Diepvens et al., 2007b) Ephedrine ...
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Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for antiobesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferatoractivated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for antiobesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.
... Capsinoids exert similar effects in increasing BAT-dependent energy expenditure as does cold exposure (Luo et al. 2012). Caffeine (1,3,7-trimethylxantine), a widely consumed plant alkaloid found in coffee, and tea has been shown to aid weight loss and increased energy expenditure in both human and animals, thus reducing the risk of type 2 diabetes (Bukowiecki et al. 1983, Dulloo et al. 1989, Astrup et al. 1990, Bracco et al. 1995, Kobayashi-Hattori et al. 2005, Bhupathiraju et al. 2013. By using a stem cell model of adipocyte browning (Velickovic et al. 2018) a physiological amount of caffeine was shown to promote UCP1 function (Velickovic et al. 2019). ...
... In another pair of studies, Dulloo et al. 28,29 investigated the effects of a caffeine-ephedrine combination vs. ephedrine as monotherapy in lean and obese human volunteers and observed that the ephedrine/ methylxanthine combination was twice as effective as ephedrine alone in increasing the fasting metabolic rate of both subject groups. The thermic effects to meals were decreased in the preobese and obese subjects, indicative of a defect in the thermic effect of feeding compared to normally lean control subjects. ...
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To determine the effects of norepinephrine (NE) or of caffeine (CAF) alone or in combination with ephedrine (EPH) were determined in groups of lean and obese LA/Ntul//-cp Rats, Body weights of obese were >> lean littermates (p=<0.01) and measures of RMR of lean > Obese (p=<0.05). The effects of caffeine, ephedrine, a caffeine+ephedrine combo, and the β- agonist epinephrine was examined. Caffeine (CAF) resulted in a 33% increase in VO2, ‘nonephedrine’ (EPH) a 48% increase, the combination CAF+EPH a 53% increase, and the NE a 33% increase in VO2. In obese rats, the increases in VO2 were of a similar percentage (21 vs 48 vs 47 % vs 31% for CAF, EPH, CAF+EPH and NE respectively although the peak responses attained in the obese tended to be of a significantly lesser absolute magnitude than were observed in the lean phenotype. The time to peak thermogenic response was similar in lean and obese phenotypes for each of the 4 treatment regimens, but the duration of the peak responses to each treatment differed between lean and obese phenotypes (Obese > lean) for CAF, EPH and the CAF+EPH combination but duration of the VO2 response was similar in both phenotypes for the NE treatment. Thus, these observations are consistent with a significant CAF-stimulated thermogenic response that was qualitatively similar to that of NE in both lean and obese phenotypes of the congenic LA/Ntul//-cp rat and which thermogenic responses were further augmented with EPH alone or in combination with CAF. Although the mechanisms of action of the pharmacologic and physiologic mechanisms elicited may differ among the three agents studied the results indicate that they are complimentary in nature in bringing about increases in parameters of nonshivering thermogenesis and thus increasing metabolic energy expenditure in both lean and obese rats. In conclusion, while caffeine as monotherapy may bring about limited weight loss, the combination of caffeine plus ephedrine was more effective in the lean and obese phenotypes of the congenic, non-diabetic LA/Ntul//-cp (Corpulent) rat.
... Moreover, in a previous study, the ingestion of caffeine increased the metabolic rate by 0.2 kJ/min and this increase lasted for 3 hours in healthy male volunteers 12 . Similar results were also reported in resting rats, where their O 2 uptake was significantly higher (P < 0.05) 2 hours after the administration of 10 mg of caffeine than that of the control 13 . In our study, we detected differences in fat oxidation for a longer period (4 h) after the acute administration of lactate and lactate-plus-caffeine. ...
Full-text available
Purpose: Although several physiological roles of lactate have been revealed in the last decades, its effects on energy metabolism and substrate oxidation remain unknown. Therefore, we investigated the effects of lactate on the energy metabolism of resting rats. Methods: Male rats were divided into control (Con; distilled water), caffeine (Caf; 10 mg/kg), L-lactate (Lac; 2 g/kg), and lactate-plus-caffeine (Lac+Caf; 2 g/ kg + 10 mg) groups. Following oral administration of supplements, resting energy expenditure (study 1), biochemical blood parameters, and mRNA expression involved in energy metabolism in the soleus muscle were measured at different time points within 120 minutes of administration (study 2). Moreover, glycogen level and Pyruvate dehydrogenase (PDH) activity were measured. Results: Groups did not differ in total energy expenditure throughout the 6 hour post-treatment evaluation. Within the first 4 hours, the Lac and Lac+Caf groups showed higher fat oxidation rates than the Con group (p<0.05). Lactate treatment decreased blood free fatty acid levels (p<0.05) and increased the mRNA expression of fatty acid translocase (FAT/CD36) (p<0.05) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) (p<0.05) in the skeletal muscle. Hepatic glycogen level in the Lac+Caf group was significantly increased (p<0.05). Moreover, after 30 and 120 minutes, PDH activity was significantly higher in lactate-supplemented groups compared to Con group (p<0.05). Conclusion: Our findings showed that Lac+Caf enhanced fat metabolism in the whole body and skeletal muscle while increasing hepatic glycogen concentration and PDH activity. This indicates Lac+Caf can be used as a potential post-workout supplement.
... In addition, these two compounds complement each other and can help you burn fat through a process called thermogenesis. In simple terms, thermogenesis is a process in which your body burns calories to produce heat using green tea extract as a drink stimulated thermogenesis and fat oxidation and thus has the potential to influence body weight and body composition via changes in both EE and substrate utilization [12,13]. ...
... We speculate that by including resting studies, the impact of CAF on fat metabolism may be less influenced by other potential factors at play during exercise (intensity, participant fitness level) and enhance the possibility to elicit more consistent metabolic effects at "lower" CAF dosages (∼3 mg/kg). To that end, a CAF dosage of only 100 mg has been shown to increase resting energy expenditure by 3%-4% although fat oxidation was not measured (Dulloo et al., 1989). The lack of a clear CAF dose-response effect has also been previously demonstrated related to endurance performance (Conger et al., 2011) and ratings of perceived exertion (Doherty & Smith, 2005), although (Spriet, 2014) suggests higher CAF doses, while not needed for central nervous system antagonism of adenosine (i.e., influencing performance and perceived exertion), might be necessary for metabolic actions (e.g., lipolysis). ...
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Whether caffeine (CAF) increases fat metabolism remains debatable. Using systematic review coupled with meta-analysis, our aim was to determine effects of CAF on fat metabolism and the relevant factors moderating this effect. Electronic databases PubMed, SPORTDiscus, and Web of Science were searched using the following string: CAF AND (fat OR lipid) AND (metabolism OR oxidation). A meta-analytic approach aggregated data from 94 studies examining CAF’s effect on fat metabolism assessed by different biomarkers. The overall effect size (ES) was 0.39 (95% confidence interval [CI] [0.30, 0.47], p < .001), indicating a small effect of CAF to increase fat metabolism; however, ES was significantly higher ( p < .001) based on blood biomarkers (e.g., free fatty acids, glycerol) (ES = 0.55, 95% CI [0.43, 0.67]) versus expired gas analysis (respiratory exchange ratio, calculated fat oxidation) (ES = 0.26, 95% CI [0.16, 0.37]), although both were greater than zero. Fat metabolism increased to a greater extent ( p = .02) during rest (ES = 0.51, 95% CI [0.41, 0.62]) versus exercise (ES = 0.35, 95% CI [0.26, 0.44]) across all studies, although ES was not different for studies reporting both conditions (ES = 0.49 and 0.44, respectively). There were no subgroup differences based on participants’ fitness level, sex, or CAF dosage. CAF ingestion increases fat metabolism but is more consistent with blood biomarkers versus whole-body gas exchange measures. CAF has a small effect during rest across all studies, although similar to exercise when compared within the same study. CAF dosage did not moderate this effect.
Background: Prematurity is associated with lots of comorbidities. Premature neonates also have lower bone mineral content (BMC) compared to term neonates. Apnea of prematurity is a common complication and caffeine citrate is widely used for its prevention and treatment. Caffeine also affects creatinine clearance, urine flow rate and releases calcium from its storage sites. Objectives: The primary objective was to assess BMC in preterm neonates treated with caffeine using dual energy X-ray absorptiometry (DEXA). Secondary objectives were to determine whether caffeine therapy is associated with increased incidence of nephrocalcinosis or bone fracture. Methods: Prospective observational study on 42 preterm neonates, 34 weeks' gestation or less; 22 of them received intravenous caffeine (caffeine group) and 20 did not (control group). Serum levels of calcium, phosphorus, alkaline phosphatase, magnesium, sodium, potassium, and creatinine, abdominal ultrasonography, and DEXA scan were done for all included neonates. Results: BMC showed significant lower levels in the caffeine compared to control group (p = 0.017). Additionally, BMC was significantly lower in neonates who received caffeine for more than 14 days compared to those who received it for 14 days or less(p = 0.04). BMC showed significant positive correlation to birth weight, gestational age, serum P and significant negative correlation to serum ALP. Caffeine therapy duration was negatively correlated to BMC (r = -0.370, p = 0.000) and positively correlated to serum ALP levels (r = 0.667, p = 0.001). None of the neonates had nephrocalcinosis. Conclusions: Caffeine administration for more than 14 days in preterm neonates may be associated with lower BMC but not nephrocalcinosis or bone fracture.
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Daily metabolic rates of 16 post-obese women and 16 matched, lean controls were measured at three different levels of activity in a room respirometer. Both groups had similar height, weight, age, and other anthropometric indices. Results show that the post-obese have metabolic rates approximately 15% lower than their controls at any level of activity. They also eat less. Slimmed-down, obese women have a normal body composition. For both groups, aerobic exercise did not have a prolonged stimulatory effect on metabolic rate after the exercise had finished. Mild exercise was more effective than aerobic exercise in increasing daily metabolic rate because it could be comfortably sustained for a longer time. Implications of these findings are discussed in relation to the etiology and treatment of obesity.
Administration of a thermogenic mixture of ephedrine, caffeine and theophylline to grossly obese (11-12 mo old) fa/fa Zucker rats led to a rapid decline in their body weight, which reached lean levels within 9-10 wk, and this postobese weight was maintained for another 5-6 wk. Compared to the no-drug obese controls (O-ND), food intake was reduced by 70% during the dynamic phase of weight loss and by 50% during the postobese period in the food-restricted animals (O-FR) and by about 40% during both phases in the ephedrine/methylxanthines (O-E/Mx) animals. Energy expenditure in the O-FR group was lower than in the O-E/Mx group by 25-33%. Analysis of body composition showed that body fat in both O-FR and O-E/Mx groups was much lower than in the O-ND group, by 2.5- and 4-fold, respectively, and body protein was lower by 50 and 28%, respectively. Thus, compared to the O-ND group, the fat:protein ratio was only 25% lower in the O-FR animals but was three times less in the O-E/Mx group. These findings demonstrate that in the fa/fa rat a mixture of ephedrine and methylxanthines reduces food intake but also minimizes the fall in metabolic rate that usually accompanies such an energy deficit, effects that led to a reversal of their gross obesity. The ability of ephedrine alone or in combination with methylxanthines to reverse obesity in animal models with dietary and hypothalamic etiologies is thus extended to the obesity resulting from the inheritance of a single-gene recessive defect.
The thermogenic effect of an over-the-counter preparation containing 22 mg ephedrine, 30 mg caffeine and 50 mg theophylline was investigated in human volunteers with a predisposition to obesity and also in the lean. The ephedrine/methylxanthines mixture was twice as effective as ephedrine alone in increasing the fasting metabolic rate of both subject groups, and it normalized the reduced thermogenic response to a 1.25-MJ meal observed in those predisposed to obesity. Measurements of 24-h energy expenditure in a respirometer indicate that the mixture had no effect on the daily metabolic rate of the lean, but was effective in causing a significant 8 percent increase in the 24-h energy expenditure of those subjects predisposed to obesity. These studies indicate that relatively mild doses of dietary methylxanthines in combination with ephedrine can raise daily energy expenditure of those predisposed to obesity, mainly by correcting their defective thermogenic response to food. Such ephedrine/methylxanthine preparations could be useful as aids in the treatment of obesity.
A thermogenic mixture containing ephedrine and methylxanthines was administered to 8-wk-old genetically obese fa/fa rats (O-E/Mx group) for a period of 15 wk. Their energy balance and the final body composition were compared with an untreated ad libitum-fed (O-AL) group, as well as to other fa/fa obese animals that were either pair fed to lean controls (O-PF group), or that were food restricted to such an extent they maintained a similar body weight to that of lean animals (O-WF group). Energy intake was elevated above lean or O-PF levels by approximately 27 and 10% in the O-AL and O-E/Mx groups, respectively, but lower by 18% in the O-WF group. Energy expenditure, compared with the lean values, was 10% higher in both the O-AL and O-E/Mx groups, but reduced by 13 and 30% in the O-PF and O-WF groups, respectively. The gain in body energy and the efficiency of energy deposition remained elevated above the lean values by 2.3- to 3.5-fold in the O-AL, O-PF, and O-WF groups but were reduced to lean levels in the O-E/Mx groups. These studies indicate that, unlike food restriction, the ephedrine-methylxanthine mixture prevents or arrests the development of the obesity in the fa/fa mutant by normalizing their energetic efficiency to that of the lean.
An over-the-counter preparation containing ephedrine, caffeine, and theophylline was examined for thermogenic anti-obesity properties. Administration of the methylxanthines to MSG-induced obese mice for 6 wk had no effect on energy balance or body composition. In contrast, treatment with ephedrine alone caused losses of 14% in body weight and 42% in body fat, effects brought about mainly by a 10% increase in energy expenditure. These changes were accentuated when ephedrine was administered together with one or both methylxanthines: energy expenditure was increased by a further 10%, and led to a reduction of about 25% in body weight and 75% in body fat, while the total food intake and body protein were unaltered. These results indicate that dietary methylxanthines like caffeine and theophylline, although alone have little effect on energy balance, can nevertheless markedly potentiate the thermogenic anti-obesity effect of ephedrine and normalize the body composition of the obese to the lean levels.
Caffeine produces enhanced oxygen consumption, an effect that may reflect an action of caffeine on brown adipose thermogenesis. In Experiment 1, adult male rats were anesthetized with 1.2 g/kg urethane and treated (IP) with either 0.9% saline or 10, 20 or 40 mg/kg caffeine (n = 4 each group). Interscapular BAT (IBAT) and rectal temperatures were recorded every minute for 10 minutes prior to and 30 minutes following drug injection. Stable IBAT and rectal temperatures were observed prior to and after saline injection whereas rats treated with 20 and 40 mg/kg caffeine exhibited moderate increases in IBAT, but not rectal, temperature. In Experiment 2, adult male rats were treated with either 0.9% saline or 10 mg/kg caffeine, anesthetized with urethane (1.2 g/kg) and treated (30 minutes after pretreatment injections) with either 0.9% saline or 10 mg/kg dl-phenylpropanolamine (dl-PPA). A combination of caffeine and dl-PPA produced significantly greater BAT thermogenesis than just dl-PPA alone. The implications of these data for the inclusion of caffeine in over-the-counter diet-pills are discussed.