J Appl Physiol 92: 513–518, 2002;
10.1152/japplphysiol.00255.2001.
Opposite actions of caffeine and creatine on muscle
relaxation time in humans
P. HESPEL, B. OP ‘T EIJNDE, AND M. VAN LEEMPUTTE
Exercise Physiology and Biomechanics Laboratory, Department of Kinesiology,
Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven,
Tervuursevest 101, B-3001 Leuven, Belgium
Received 20 March 2001; accepted in final form 11 October 2001
Hespel, P., B. Op ‘t Eijnde, and M. Van Leemputte.
Opposite actions of caffeine and creatine on muscle relaxation time in humans. J Appl Physiol 92: 513–518, 2002;
10.1152/japplphysiol.00255.2001.—The effect of creatine and
caffeine supplementation on muscle torque generation and
relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of
Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were
measured during an exercise test consisting of 30 intermittent contractions of musculus quadriceps (2 s stimulation, 2 s
rest) that were induced by electrical stimulation. According
to a double-blind randomized crossover design, subjects (n ⫽
10) performed the exercise test before (pretest) and after
(posttest) creatine supplementation (Cr, 4 ⫻ 5 g/day, 4 days),
short-term caffeine intake (Caf, 5 mg 䡠 kg⫺1 䡠 day⫺1, 3 days),
creatine supplementation ⫹ short-term caffeine intake
(Cr⫹Caf), acute caffeine intake (ACaf, 5 mg/kg) or placebo.
Compared with placebo, Cr shortened RT by ⬃5% (P ⬍ 0.05).
Conversely, Caf increased RT (⫹⬃10%, P ⬍ 0.05), in particular as RT increased because of fatigue. RT was not significantly changed by either Cr⫹Caf or ACaf. Tmax and CT were
similar during all experimental conditions. Initial Tmax was
⬃20% of voluntary maximal isometric contraction force,
which was not different between treatments. It is concluded
that Caf intake (3 days) prolongs muscle RT and by this
action overrides the shortening of RT due to creatine supplementation.
exercise; muscle contractions; ergogenics; diet
CAFFEINE AND CREATINE are popular ergogenic substances
in athletic populations. Both substances occur in the
normal diet yet are ingested as supplements by athletes for the express purpose of enhancing exercise
performance (for recent reviews on these issues, see
Refs. 22 and 24).
It is well established that caffeine, even at dosages that
are well below the reference limit set by the International
Olympic Committee, can enhance endurance exercise
performance (22). Investigations examining its effects
in short high-intensity activities requiring strength
and power have produced inconsistent results. Caffeine enhanced maximum power output in 6-s sprints
(1) but not in a 30-s Wingate test (5, 13). In a study by
Address for reprint requests and other correspondence: P. Hespel,
F.L.O.K. - K.U. Leuven, Exercise Physiology Laboratory, Tervuursevest
101, B-3001 Heverlee, Belgium.
http://www.jap.org
Greer et al. (13), healthy volunteers performed four
30-s Wingate sprints with 4-min rest intervals in between. Caffeine did not impact on power output during
the first 2 sprints, but it was detrimental to performance in the latter 2 exercise bouts. Findings with
regard to the impact of caffeine on strength activities
are even more controversial. However, this is at least
partly due to lack of well-controlled studies addressing
this issue. Interestingly, Kalmar and Cafarelli (16)
recently reported caffeine to increase time to fatigue
during voluntary knee extensions at 50% of maximal
voluntary contraction (MVC) force by ⬃25%, whereas
voluntary activation increased by 3.5%. Neither the
force-electromyogram relationship nor motor unit firing rates were altered by caffeine, which indicates that
the ergogenic effects of caffeine were, at least in part,
mediated by local mechanisms. Accordingly, two other
studies found caffeine intake in humans to potentiate
muscle force production during low-frequency nerve
stimulation (18, 23).
More than 50 studies over the last 10 yr have addressed the effects of creatine supplementation on
high-intensity exercise performance. Data consistency
has been curtailed by results of poorly controlled studies. However, the body of evidence clearly indicates
that short-term creatine supplementation (20–30
g/day, 4–7 days) can increase maximal force and power
output during short maximal exercise bouts, in particular during intermittent exercise but not during endurance exercise (24). Furthermore, creatine supplementation in conjunction with heavy resistance
training has the potential to stimulate muscle hypertrophy and maximal muscle force (27). This effect is
important to any sport involving heavy resistance
training.
The physiological mechanisms by which caffeine and
creatine elicit their ergogenic effects are poorly understood. The failure of central neural as well as systemic
metabolic mechanisms to explain the effects of caffeine
in short maximal exercise has prompted interest in its
local actions on muscle cells. Our laboratory has demonstrated in perfused rat muscles that physiological
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513
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CAFFEINE, CREATINE, AND MUSCLE RELAXATION TIME
concentrations of caffeine stimulate glycogenolysis in
glycolytic muscle fibers during electrical stimulation
(29). However, glycogen availability is not limiting
high-intensity exercise performance. In a recent study,
Tarnopolsky and Cupido (23) demonstrated caffeine
ingestion to potentiate muscle force production during
low-frequency tetanic stimulation. A putative mechanism to explain this finding is that caffeine at physiological concentrations facilitates sarcoplasmic reticulum calcium release. The beneficial effect of caffeine
intake on performance during electrically induced cycling in tetraplegic patients also indicates a direct
action of the drug on skeletal muscle (20). In fact, our
laboratory’s earlier finding that caffeine intake can
negate the ergogenic effect of oral creatine supplementation (26) also supports a local mechanism of action of
caffeine. The exact cellular mechanisms linking increased intracellular creatine content in muscle due to
creatine supplementation (14, 27, 28) with enhanced
contractile performance (12, 26, 27) remain largely
unexplained. However, it is obvious that increased
creatine uptake by muscle fibers during creatine supplementation initiates intracellular responses that
eventually result in ergogenic effects.
Our laboratory has recently reported that creatine
supplementation shortened relaxation time (RT) during intermittent maximal isometric muscle contractions (25). Sarcoplasmic reticulum Ca2⫹ reuptake by
virtue of Ca2⫹-ATPase pump activity is the rate-limiting step in relaxation of mammalian muscle cells (7,
11). Thus the effect of creatine intake on relaxation
rate provides evidence to suggest that sarcoplasmic
reticulum Ca2⫹ reuptake is facilitated in creatineloaded muscle. If extracellular caffeine concentrations
established by oral caffeine intake are indeed effective
to enhance Ca2⫹ release from the sarcoplasmic reticulum (23), then caffeine administration conceivably
might undo the effect of creatine supplementation to
facilitate muscle relaxation. Moreover, because caffeine can counteract the ergogenic effect of creatine
supplementation, such an observation would provide
indirect evidence to support our hypothesis that shortening of muscle relaxation is important to the ergogenic impact of creatine supplementation during sprint
exercise.
Therefore, in the present study we investigated the
effects of creatine and caffeine supplementation, alone
or in combination, on muscle RT. A recent study in
isolated rat hearts has shown that the adaptations of
contractile function may markedly differ depending on
the duration of caffeine exposure (17). Therefore, we
compared the effects of acute and short-term (3 days)
caffeine administration. Furthermore, to eliminate
neural effects, we studied muscle RT during electrically induced contractions. This approach is valid because the rate-limiting step of muscle relaxation,
notably sarcoplasmic reticulum Ca2⫹ reuptake, is independent of whether contractions are either voluntary or induced by electrical stimulation (7, 11). We
used isometric contractions because doing so yields
highly reproducible measurements of muscle RT (25).
J Appl Physiol • VOL
MATERIALS AND METHODS
Subjects. Ten physical education students, 9 men and 1
woman, aged between 21 and 24 yr, gave their informed,
written consent to take part in the study. All subjects were
physically active, but none of them was highly trained. They
were informed of the experimental procedures to be undertaken and were instructed to abstain from any medication
and caffeine starting 1 wk before each experimental period
(28). Furthermore they were asked to avoid changes in their
usual level of physical activity and diet during the entire
study period lasting 25 wk. The local ethics committee approved the study protocol.
Study protocol. A double-blind study was performed,
whereby the subjects were assigned in random order to five
experimental protocols, each lasting 8 days (day 0 to day 7)
and separated by a washout period of 5 wk. There is good
evidence to suggest that muscle creatine stores return to
normal within 4–5 wk after cessation of creatine supplementation (27). One week before the start of the study, the
subjects reported to the laboratory to get habituated to the
test protocol. The protocol involved electrical stimulation of
the left musculus quadriceps femoris and aimed to assess
muscle activation time, isometric torque, and RT. The subjects returned to the laboratory for the pretest on day 0. One
week after the pretest (day 7), at the same time of day, the
subjects returned to the laboratory for the posttest, the procedures of which were identical to the pretest. The results of
the measurements were disclosed neither to the subjects nor
to the investigators until completion of the entire study. In
protocol A (Cr) the subjects ingested 4 ⫻ 5 g of creatine
monohydrate per day for 4 days (day 3 to day 6). It is well
established that this mode of creatine supplementation is
effective to raise muscle creatine content in young male
volunteers (14, 24). The last creatine dose preceded the
measurements on day 7 by at least 12 h. In protocol B (Caf),
on days 4, 5, and 6 the subjects received a single dose of 5 mg
caffeine 䡠 kg body wt⫺1 䡠 day⫺1. The caffeine capsules were
ingested at breakfast. The last dose of caffeine preceded the
measurements on day 7 by at least 20 h. Protocol C (Cr⫹Caf)
was a combination of protocols A and B. Thus, on days 4, 5,
and 6, in addition to the creatine supplements, the subjects
were administered a single dose of 5 mg caffeine 䡠 kg body
wt 䡠 ⫺1 䡠 day⫺1. Similar to protocol B, the caffeine capsules
were ingested at breakfast together with a creatine supplement. Our laboratory had previously demonstrated that such
combination of creatine and caffeine counteracts the beneficial impact of creatine supplementation alone on muscle
power output during maximal intermittent muscle contractions (26). Protocol D was an acute caffeine condition (ACaf):
the subjects received 5 mg caffeine/kg body wt 1 h before the
exercise test on day 7 only. In protocol E, the subjects ingested placebo supplements from day 3 to day 7. The creatine
powders were flavored by the addition of citrate (60 mg/g
creatine) and maltodextrine (940 mg/g creatine). The placebo
powders contained maltodextrine and citrate (40 mg/g maltodextrine). The subjects were instructed to dissolve the
powder supplements in ⬃150 ml of hot water immediately
before ingestion. Creatine and placebo powders were identical in taste and appearance. Placebo capsules contained
maltodextrine. The administration schedule of the powder
supplements (creatine or placebo) and capsules (caffeine or
placebo) was identical for all experimental conditions.
Electrical stimulation protocol. The subjects arrived at the
laboratory in the morning between 8:00 and 12:00 AM. First
their body weight was measured. They were then seated on a
chair, rotated 30° backward, with the left leg supported at
92 • FEBRUARY 2002 •
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CAFFEINE, CREATINE, AND MUSCLE RELAXATION TIME
the level of the popliteal space. An isokinetic dynamometer,
instrumented with a torque transducer (Lebow 1605, 0.05%
accuracy level) and connected with a rigid lever arm, was
positioned lateral to the knee such that its axis was aligned
with the knee joint axis. The leg was tightly strapped to the
lever arm of the system proximal to the ankle joint. The lever
arm was rotated to a knee angle of 90°. The positions of the
knee support and of the axis of the isokinetic dynamometer
and the length of the lever arm were noted for each individual, to be set identically for the pre- and posttests for all
experimental conditions. Two electrodes (6 ⫻ 4 cm) were then
fitted on m. quadriceps femoris. The proximal electrode was
positioned at one-third of the line connecting the anterior
superior spina iliaca and the center of the upper edge of the
patella, with the knee in full extension (180°). The distal
electrode was positioned 15 cm distal to the proximal electrode. After a standardized 5-min warmup, the subject performed three voluntary maximal isometric knee extensions
(3 s) at a knee angle of 90°, interspersed with 10-s rest
intervals, to determine MVC. Thereafter, the rectus femoris
muscle was electrically stimulated (Multistim ESP, Fysiomed, Edegem, Belgium) with 2-s trains, composed of 0.5-ms
unipolar square-wave pulses firing at 60 Hz. Over a maximum of 5 contractions (10-s rest pauses), the stimulation
intensity was gradually increased to obtain the target force of
20% of the previously determined maximal voluntary isometric knee-extension torque, or less in case of excessive pain
(n ⫽ 2, force ⫽ ⬃15% of MVC). After 5 min of rest, 30
electrically induced contractions (2 s) were initiated with a
2-s rest-interval between the contractions. For each contraction, both torque and the activation pattern of the electrical
stimulator were digitized at 500 Hz and stored to disk for
later analysis. Stimulation intensity was on average 95 mA
(range 56–110 mA) and was identical for the five experimental conditions.
Data analysis. The torque from each contraction was characterized by three parameters: 1) maximal torque (Tmax, in
N 䡠 m); 2) contraction time (CT, in ms), which was defined as
the time needed to increase muscle torque from 0.25 to 0.75
of Tmax, and 3) RT (in ms), which was defined as the time
needed to reduce torque from 0.75 to 0.25 of Tmax. Our
laboratory previously reported that the intraday reliability
for CT and RT measurements with the present methodology
is 0.94 and 0.96, respectively. Corresponding values for interday reliability were 0.92 and 0.95 (25). The subjects performed 30 contractions induced by electrical stimulation.
Mean CT, Tmax, and RT were calculated for the entire series
of 30 contractions, as well as per six contractions (1–6, 7–12,
13–18, 19–24, 25–30) to consider the effects of fatigue. Treatment effects were evaluated by either two-way (means of 30
contractions) or two-way (means per 6 contractions) repeated-measures analyses of variance, which were covariate adjusted for the pretest values. Tukey’s tests were used as a
post hoc test to locate differences among means. The level of
statistical significance was set at P ⱕ 0.05. All statistical
procedures were performed with use of Statistica software
(Statsoft, Tulsa, OK).
RESULTS
Maximal knee-extension torque. In placebo, initial
maximal knee-extension torque (Tmax; mean of contractions 1–6) was 28 ⫾ 3 N 䡠 m in the pretest and 30 ⫾ 3
N 䡠 m in the posttest (Table 1). Tmax decreased (P ⬍
0.05) by ⬃40% from the start to the end of the contraction series. Thus final Tmax (mean of contractions 25–
30) was 17 ⫾ 2 N 䡠 m during the pretest vs. 19 ⫾ 3 N 䡠 m
J Appl Physiol • VOL
Table 1. Effect of creatine and caffeine intake on
maximal torque during intermittent electrical
stimulation of m. quadriceps
Number of Contractions
Pl
Pretest
Posttest
Cr
Pretest
Posttest
Caf
Pretest
Posttest
Cr ⫹ Caf
Pretest
Posttest
ACaf
Pretest
Posttest
1–6
7–12
13–18
19–24
25–30
1–30
28 ⫾ 3
30 ⫾ 3
21 ⫾ 3
26 ⫾ 3
19 ⫾ 3
22 ⫾ 3
18 ⫾ 2
20 ⫾ 3
17 ⫾ 2
19 ⫾ 3
20 ⫾ 3
23 ⫾ 3
32 ⫾ 2
31 ⫾ 2
25 ⫾ 2
23 ⫾ 2
20 ⫾ 3
18 ⫾ 2
19 ⫾ 2
17 ⫾ 2
18 ⫾ 2
16 ⫾ 2
23 ⫾ 2
21 ⫾ 1
29 ⫾ 4
28 ⫾ 2
22 ⫾ 3
22 ⫾ 2
20 ⫾ 2
19 ⫾ 2
18 ⫾ 2
17 ⫾ 2
18 ⫾ 2
15 ⫾ 1
21 ⫾ 2
20 ⫾ 2
28 ⫾ 3
28 ⫾ 2
21 ⫾ 2
23 ⫾ 2
18 ⫾ 2
18 ⫾ 1
16 ⫾ 1
17 ⫾ 1
15 ⫾ 1
17 ⫾ 2
20 ⫾ 2
21 ⫾ 2
31 ⫾ 4
31 ⫾ 3
23 ⫾ 2
24 ⫾ 2
18 ⫾ 2
21 ⫾ 2
18 ⫾ 2
19 ⫾ 1
17 ⫾ 2
19 ⫾ 1
21 ⫾ 2
23 ⫾ 2
Values (N 䡠 m) are means ⫾ SE of 10 observations. Electrical
stimulation induced 30 contractions of m. quadriceps (2-s stimulation, 2-s rest). Mean maximal torque production was calculated per 6
contractions (1–6, 7–12, 13–18, 19–24, 25–30) and for the entire
series of 30 contractions (1–30). Between the pretest and the posttest
the subjects ingested for 5 days either creatine (Cr, 4 ⫻ 5 g/day) or
caffeine [Caf, 5 mg/kg body weight (bw) per day] alone, or creatine
plus caffeine (Cr ⫹ Caf), or placebo (Pl). In the acute caffeine condition they received a single caffeine dose (ACaf, 5 mg/kg bw) 1 h before
the electrical stimulation. See MATERIALS AND METHODS for further
details.
during the posttest. Tmax was similar between all experimental conditions throughout the contraction series, during both the pretest and the posttest. Immediately before the start of the electrical stimulation
protocol, MVC was measured. MVC in placebo was
similar in the pretest (157 ⫾ 10 N 䡠 m) and in the
posttest (159 ⫾ 10 N 䡠 m), and there were no differences
between the experimental conditions at any time (data
not shown). Thus initial Tmax during electrical stimulation consistently amounted to 18–20% of MVC.
CT. Initial CT in placebo was 79 ⫾ 4 ms during the
pretest vs. 80 ⫾ 4 ms during the posttest (Table 2). CT
lengthened (P ⬍ 0.05) with increasing number of contractions. At the end of the contraction series, CT was
increased to 91 ⫾ 4 and 94 ⫾ 3 ms in the pretest and
posttest, respectively. There were no significant differences for CT between the treatments at any time.
RT. Initial RT was 58 ⫾ 3 ms in the pretest and 60 ⫾
3 ms in the posttest (Table 3). RT gradually increased
(P ⬍ 0.05) throughout the stimulation protocol. RT
during the final six contractions of the series was on
average 86 ⫾ 5 and 89 ⫾ 4 ms during the pretest and
posttest, respectively. Furthermore, RTs at the pretest
were similar for all experimental conditions. Compared
with placebo, during the posttest mean RT was lower
in Cr (P ⬍ 0.05) and tended to be higher in Caf (P ⫽
0.09). Compared with Cr, short-term caffeine intake,
alone (Caf) or in conjunction with creatine intake
(Cr⫹Caf), resulted in longer RTs. This lengthening of
RT during Caf and Cr⫹Caf was most prominent during
the final stage of the contraction series (Table 3). RT
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CAFFEINE, CREATINE, AND MUSCLE RELAXATION TIME
Table 2. Effect of creatine and caffeine intake on
muscle contraction time during intermittent electrical
stimulation of m. quadriceps
Number of Contractions
Pl
Pretest
Posttest
Cr
Pretest
Posttest
Caf
Pretest
Posttest
Cr ⫹ Caf
Pretest
Posttest
ACaf
Pretest
Posttest
1–6
7–12
13–18
19–24
25–30
1–30
79 ⫾ 4
80 ⫾ 4
90 ⫾ 3
85 ⫾ 4
91 ⫾ 4
92 ⫾ 3
94 ⫾ 4
93 ⫾ 4
91 ⫾ 4
94 ⫾ 3
89 ⫾ 3
89 ⫾ 3
74 ⫾ 2
78 ⫾ 2
88 ⫾ 4
87 ⫾ 3
93 ⫾ 4
91 ⫾ 3
94 ⫾ 5
96 ⫾ 4
90 ⫾ 6
100 ⫾ 5
88 ⫾ 4
90 ⫾ 2
82 ⫾ 3
83 ⫾ 2
85 ⫾ 4
91 ⫾ 2
86 ⫾ 2
96 ⫾ 2
92 ⫾ 3
99 ⫾ 5
94 ⫾ 5
102 ⫾ 5
88 ⫾ 3
94 ⫾ 3
81 ⫾ 2
77 ⫾ 3
88 ⫾ 3
88 ⫾ 4
89 ⫾ 4
89 ⫾ 3
94 ⫾ 5
94 ⫾ 4
94 ⫾ 6
93 ⫾ 4
89 ⫾ 3
88 ⫾ 3
84 ⫾ 2
82 ⫾ 3
84 ⫾ 4
88 ⫾ 3
93 ⫾ 4
90 ⫾ 3
89 ⫾ 5
97 ⫾ 3
93 ⫾ 4
96 ⫾ 5
88 ⫾ 3
90 ⫾ 3
Values (ms) are means ⫾ SE of 10 observations. Electrical stimulation induced 30 contractions of m. quadriceps (2-s stimulation, 2-s
rest). Activation time was determined as the time to increase torque
from 25 to 75% of maximal. Mean activation time was calculated per
6 contractions (1–6, 7–12, 13–18, 19–24, 25–30) and for the entire
series of 30 contractions (1–30). See MATERIALS AND METHODS for
further details. In between the pretest and the posttest the subjects
ingested for 5 days either creatine (Cr, 4 ⫻ 5 g/day) or caffeine (Caf,
5 mg/kg bw per day) alone, or creatine plus caffeine (Cr ⫹ Caf), or
placebo (Pl). In the acute caffeine condition they received a single
caffeine dose (ACaf, 5 mg/kg bw) 1 h before the electrical stimulation.
reduces the functional capacity of sarcoplasmic reticulum Ca2⫹ ATPase.
It is intriguing that short-term caffeine supplementation (5 mg 䡠 kg⫺1 䡠 day⫺1 for 3 days before the posttest)
but not acute caffeine intake (5 mg/kg bolus 1 h before
the posttest) impaired muscle relaxation. The last dose
of caffeine during the Caf protocol preceded the experiments by at least 20 h. Hence plasma caffeine was
largely washed out at the time relaxation rates were
measured (3). Our present data thus clearly show that
the effects of caffeine on muscle relaxation can be
different depending on the administration regimen
used. In keeping with such contention, in a recent
study 8 wk of caffeine treatment (10 mg/kg ip, twice per
day) in rats was found initially to decrease myocardial
contractility yet thereafter to increase it (17). The
mechanism underlying this time phenomenon cannot
be explained from the present findings. Caffeine at
physiological concentrations (⬍75 ␮M) is known to
exert its actions primarily by inhibiting cellular adenosine receptors (9, 10), and A2 subtype adenosine receptors are present in the plasma membrane and cytosol of muscle cells (19). In addition, adenosine has
been found to be involved in relaxation of vascular
smooth muscle cells by acting on intracellular A2 adenosine receptors (4). Furthermore, studies in rats have
shown that chronic dietary caffeine administration not
only can markedly increase plasma adenosine concentration (6) but also can change adenosine receptor
was not significantly different at any time between Caf
and Cr⫹Caf. During ACaf, mean RT was not significantly different from placebo. However, on the one
hand RTs during ACaf were longer than during Cr
(P ⬍ 0.05); on the other hand they were shorter than
during Caf (P ⬍ 0.05).
Table 3. Effect of creatine and caffeine intake on
muscle relaxation time during intermittent electrical
stimulation of m. quadriceps
DISCUSSION
Pl
The present study confirms that oral creatine supplementation shortens muscle RT in humans (25). During a series of 30 muscle contractions induced by intermittent electrical stimulation, RT after creatine
supplementation was reduced by 5% and was significantly shorter than after placebo. RTs exhibited the
normal increase with fatigue (8) in either group, yet
they were consistently lower during creatine supplementation than during placebo (Table 3). Furthermore,
consistent with our earlier observations, the shortening of RT occurred in the absence of any change of
either peak force production (Table 1) or CT (Table 2).
Interestingly, the intake of caffeine (5 mg/kg body wt)
together with one of the daily creatine supplements for
a period of 3 days counteracted the beneficial effect of
creatine intake on RT, and this inhibitory effect was
enhanced by fatigue. The fatigue-induced lengthening
of RT was greater after caffeine intake than during
placebo. Slowing of relaxation in fatigued muscle has
been explained by inhibition of sarcoplasmic reticulum
Ca2⫹-ATPase activity because of falling pH and ATP
affinity (8, 11). Our findings thus suggest that caffeine
J Appl Physiol • VOL
Number of Contractions
Pretest
Posttest
Cr
Pretest
Posttest
Caf
Pretest
Posttest
Cr ⫹ Caf
Pretest
Posttest
ACaf
Pretest
Posttest
1–6
7–12
13–18
19–24
25–30
1–30
58 ⫾ 3
60 ⫾ 3
70 ⫾ 4
71 ⫾ 4
79 ⫾ 4
81 ⫾ 4
83 ⫾ 4
86 ⫾ 4
86 ⫾ 5
89 ⫾ 4
75 ⫾ 4
77 ⫾ 4
57 ⫾ 1
53 ⫾ 2
70 ⫾ 3
65 ⫾ 3
80 ⫾ 4
76 ⫾ 4
86 ⫾ 4
81 ⫾ 4
88 ⫾ 5
83 ⫾ 4
76 ⫾ 3
72 ⫾ 3*
58 ⫾ 2
62 ⫾ 2
68 ⫾ 2
72 ⫾ 2
76 ⫾ 3
82 ⫾ 2
80 ⫾ 4 83 ⫾ 5
92 ⫾ 4† 99 ⫾ 5*†
73 ⫾ 3
81 ⫾ 3†
59 ⫾ 2
62 ⫾ 2
71 ⫾ 3
73 ⫾ 3
79 ⫾ 4
82 ⫾ 3
83 ⫾ 4
88 ⫾ 4
84 ⫾ 5
96 ⫾ 5†
75 ⫾ 3
80 ⫾ 3*†
57 ⫾ 2
59 ⫾ 2
69 ⫾ 2
70 ⫾ 2
77 ⫾ 3
80 ⫾ 3
80 ⫾ 4
86 ⫾ 3
85 ⫾ 4
90 ⫾ 4
74 ⫾ 2
77 ⫾ 3†
Values (ms) are means ⫾ SE of 10 observations. Electrical stimulation induced 30 contractions of m. quadriceps (2-s stimulation, 2-s
rest). Relaxation time was determined as the time to decrease torque
from 75 to 25% of maximal. Mean relaxation time was calculated per
6 contractions (1–6, 7–12, 13–18, 19–24, 25–30) and for the entire
series of 30 contractions (1–30). See MATERIALS AND METHODS for
further details. In between the pretest and the posttest the subjects
ingested for 5 days either creatine (Cr, 4 ⫻ 5 g/day) or caffeine (Caf,
5 mg/kg bw per day) alone, or creatine plus caffeine (Cr ⫹ Caf), or
placebo (Pl). In the acute caffeine condition subjects received a single
caffeine dose (ACaf, 5 mg/kg bw) 1 h before the electrical stimulation.
* P ⬍ 0.05, significant treatment effect compared with placebo;
† P ⬍ 0.05, significant treatment effect compared with creatine.
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CAFFEINE, CREATINE, AND MUSCLE RELAXATION TIME
action in peripheral cells (30). However, the impact of
short-term caffeine intake and withdrawal on adenosine receptor distribution and signaling in human skeletal musculature is at present unknown.
It has been previously demonstrated in humans that
caffeine intake at a rate (4–7 mg/kg body wt) that
corresponds to the present dosage (5 mg/kg body wt)
can potentiate contraction force in fatigued muscles
during low-frequency electrical stimulation (20 Hz) but
not during high-frequency stimulation (40 Hz; Ref. 18,
23). This observation can probably be explained by the
fact that physiological caffeine concentrations can partially counteract (21) the impairment of calcium release from the sarcoplasmic reticulum ryanodine receptor occurring in muscles fatigued by low-frequency
electrical stimulation (2). Conversely, muscle fatigue
during electrical stimulation at higher frequencies has
been attributed to reduction in electrical activity of the
muscle, which means proximal to the ryanodine receptor (2). Consistent with the above observations, during
the high-frequency (60 Hz) electrical stimulation protocol used here caffeine did not impact on either the
rate (CT) or magnitude (Tmax) of muscle tension development either in the absence or presence of fatigue
(Tables 1 and 2).
The exercise model used in the present study was not
suitable to evaluate the ergogenic effects of creatine
supplementation. Creatine supplementation has been
found to be effective to improve performance during
repetitive high-power output exercise bouts (24) but
not during isometric muscle contractions (25, 26). Nevertheless, we used isometric contractions for the express purpose of obtaining highly reliable measurements of muscle RT (25), which in our hands is
impossible during dynamic muscle contractions (Van
Leemputte, unpublished observations). Still, our findings provide indirect evidence to suggest that facilitation of muscle relaxation may be important to the
ergogenic action of creatine supplementation. First, we
clearly show here that caffeine negates the beneficial
effect of creatine loading on muscle RT. Second, our
laboratory has previously reported that short-term caffeine administration, according to an identical intake
regimen as used here, entirely counteracted the ergogenic effect of creatine loading in maximal intermittent
muscle contractions (26). Furthermore, from a theoretical point of view muscle relaxation rate is conceivably
important to power production during “sprint” exercise. First, during fast repetitive concentric muscle
contractions, recovery time from the previous contraction is very critical to maximal force output during the
next contraction (15). Second, it is reasonable to assume that shortening of RT might increase the number
of actomyosin activation cycles per unit of time and
thereby power output.
Finally, it is important to mention that muscle creatine content was not measured in the present study.
However, the creatine and caffeine supplementation
regimens used here were adopted from an earlier study
by our laboratories in similar subjects (26). In the
J Appl Physiol • VOL
517
latter study, creatine alone and creatine plus caffeine
administration caused a similar ⬃5% increase of muscle PCr content assessed by 31P-NMR spectroscopy.
Thus the differential impact of creatine and caffeine on
muscle relaxation is not related to differences of intracellular creatine content in muscle cells.
In conclusion, the present study shows that shortterm caffeine intake, but not acute caffeine intake,
inhibits muscle relaxation. This negative impact of
caffeine on RT counteracts the beneficial effect of creatine supplementation on muscle RT.
This study was supported by a grant from the Fonds voor Wetenschappelijke Onderzoek Vlaanderen (grant no. G.0331.98). Creatine
powder (Creatine Fuel, Twin Laboratories, New York, NY) was
kindly provided by MJJ Power, Brussels, Belgium.
REFERENCES
1. Anselme F, Collomp K, Mercier B, Ahmaidi S, and Préfaut
C. Caffeine increases maximal anaerobic power and blood lactate
concentration. Eur J Appl Physiol 65: 188–191, 1992.
2. Bigland-Ritchie B, Jones DA, and Woods JJ. Excitation frequency and muscle fatigue: electrical responses during human voluntary and stimulated contractions. Exp Neurol 64: 414–427, 1979.
3. Burg A. Physiological disposition of caffeine. Drug Metab Rev 4:
199–228, 1975.
4. Collis MG and Brown CM. Adenosine relaxes the aorta by
interacting with an A2 receptor and an intracellular site. Eur
J Pharmacol 96: 61–69, 1983.
5. Collomp K, Ahmaidi S, Audran M, Chanal JL, and Préfaut C.
Effects of caffeine ingestion on performance and anaerobic metabolism during the Wingate test. Int J Sports Med 12: 439–443, 1991.
6. Conlay LA, Conant JA, deBros F, and Wurtman R. Caffeine
alters plasma adenosine levels. Nature 389: 136, 1997.
7. Dux L. Muscle relaxation and sarcoplasmic reticulum function
in different muscle types. Rev Physiol Biochem Pharmacol 122:
69–147, 1993.
8. Fitts RH. Cellular, molecular, and metabolic basis of muscle
fatigue. In: Exercise: Regulation and Integration of Multiple
Systems, edited by Rowell LB and Shepherd JT. New York:
Oxford University Press, p. 1151–1183, 1996.
9. Fredholm BB. Adenosine, adenosine receptors and the actions
of caffeine. Pharmacol Toxicol 76: 93–101, 1995.
10. Fredholm BB, Battig K, Holmen J, Nehlig A, and Zvartau
EE. Actions of caffeine in the brain with special reference to factors
that contribute to its widespread use. Physiol Rev 51: 83–133, 1999.
11. Gillis JM. Relaxation of vertebrate skeletal muscle. A synthesis
of the biochemical and physiological approaches. Biochim Biophys Acta 811: 97–145, 1985.
12. Greenhaff PL, Casey A, Short AH, Harris R, and Söderlund K. Influence of oral creatine supplementation on muscle
torque during repeated bouts of maximal voluntary exercise in
man. Clin Sci (Colch) 84: 565–571, 1993.
13. Greer F, McLean C, and Graham TE. Caffeine, performance,
and metabolism during repeated Wingate exercise tests. J Appl
Physiol 85: 1502–1508, 1998.
14. Harris RC, Söderlund K, and Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by
creatine supplementation. Clin Sci (Colch) 83: 367–374, 1992.
15. Herzog W and Leonard TR. Depression of cat soleus forces
following isokinetic shortening. J Biomech 30: 865–872, 1997.
16. Kalmar JM and Cafarelli E. Effects of caffeine on neuromuscular function. J Appl Physiol 87: 801–808, 1999.
17. Kapelko VI, Lakomkin VL, Studneva IM, and Pisarenko
OI. Effects of prolonged caffeine consumption on cardiac contractile function in rats. J Cardiovasc Pharmacol 36: 669–675, 2000.
18. Lopes JM, Aubier M, Jardim J, Aranda JV, and Macklem
PT. Effect of caffeine on skeletal muscle function before and
after fatigue. J Appl Physiol 54: 1303–1305, 1983.
92 • FEBRUARY 2002 •
www.jap.org
518
CAFFEINE, CREATINE, AND MUSCLE RELAXATION TIME
19. Lynge J and Hellsten Y. Distribution of adenosine A1, A2a and
A2b receptors in human skeletal muscle. Acta Physiol Scand 169:
283–290, 2000.
20. Mohr T, Van Soeren M, Graham TE, and Kjær M. Caffeine
ingestion and metabolic responses of tetraplegic humans during
electrical cycling. J Appl Physiol 85: 979–985, 1998.
21. Penner R, Neher E, Takeshima H, Nishimura S, and Numa
S. Functional expression of the calcium release channel from
skeletal muscle ryanodine receptor cDNA. FEBS Lett 259: 217–
221, 1989.
22. Spriet LL. Caffeine and performance. Int J Sport Nutr 5: S84–
S99, 2000.
23. Tarnopolsky M and Cupido C. Caffeine potentiates
low-frequency skeletal muscle force in habitual and nonhabitual caffeine consumers. J Appl Physiol 89: 1719–1724,
2000.
24. Terjung RL, Clarkson PM, Eichner ER, Greenhaff PL,
Hespel P, Israel RG, Kraemer WJ, Meyer RA, Spriet LL,
Tarnopolsky MA, Wagenmakers AJM, and Williams MH.
The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 32: 706–717, 2000.
J Appl Physiol • VOL
25. Van Leemputte M, Vandenberghe K, and Hespel P. Shortening of muscle relaxation time after creatine loading. J Appl
Physiol 86: 840–844, 1999.
26. Vandenberghe K, Gillis N, Van Leemputte M, Van Hecke
P, Vanstapel F, and Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 80:
452–457, 1996.
27. Vandenberghe K, Goris M, Van Hecke P, Van Leemputte
M, Vangerven L, and Hespel P. Long-term creatine intake is
beneficial to muscle performance during resistance training.
J Appl Physiol 83: 2055–2063, 1997.
28. Vandenberghe K, Van Hecke P, Van Leemputte M, Vanstapel F, and Hespel P. Phosphocreatine resynthesis is not
affected by creatine loading. Med Sci Sports Exerc 31: 236–242,
1999.
29. Vergauwen L, Richter EA, and Hespel P. Adenosine exerts a
glycogen-sparing action in contracting rat skeletal muscle. Am J
Physiol Endocrinol Metab 272: E762–E768, 1997.
30. Zhang Y and Wells JN. The effects of chronic caffeine administration on peripheral adenosine receptors. J Pharmacol Exp
Ther 254: 757–763, 1990.
92 • FEBRUARY 2002 •
www.jap.org