Effects of creatine supplementation on the energy cost of

muscle contraction: a 31P-MRS study

Sinclair A. Smith, Scott J. Montain, Ralph P. Matott, Gary P. Zientara, Ferenc A.
Jolesz and Roger A. Fielding
J Appl Physiol 87:116-123, 1999.

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Effects of creatine supplementation on the energy cost
of muscle contraction: a 31P-MRS study
SINCLAIR A. SMITH,1 SCOTT J. MONTAIN,2 RALPH P. MATOTT,2
GARY P. ZIENTARA,3 FERENC A. JOLESZ,3 AND ROGER A. FIELDING1
1Department of Health Sciences, Sargent College of Health and Rehabilitation Sciences,
Boston University, Boston 02215; 2United States Army Research Institute of Environmental
Medicine, Natick 01760; and 3Department of Radiology, Brigham and Women’s Hospital
and Harvard Medical School, Boston, Massachusetts 02115
Smith, Sinclair A., Scott J. Montain, Ralph P. Matott,
Gary P. Zientara, Ferenc A. Jolesz, and Roger A. Field-
ing. Effects of creatine supplementation on the energy cost of
muscle contraction: a 31P-MRS study. J. Appl. Physiol. 87(1):
116–123, 1999.—Five women and 3 men (29.8 ⫾ 1.4 yr)
performed dynamic knee-extension exercise inside a mag-
netic resonance system (means ⫾ SE). Two trials were
performed 7–14 days apart, consisting of a 4- to 5-min
exhaustive exercise bout. To determine quadriceps cost of
contraction, brief static and dynamic contractions were per-
formed pre- and postexercise. 31P spectra were used to
determine pH and relative concentrations of Pi, phosphocre-
atine (PCr), and ␤ATP. Subjects consumed 0.3 g · kg⫺1 · day⫺1
of a placebo (trial 1) or creatine (trial 2) for 5 days before each
trial. After creatine supplementation, resting ⌬PCr increased
from 40.7 ⫾ 1.8 to 46.6 ⫾ 1.1 mmol/kg (P ⫽ 0.04) and PCr
during exercise declined from ⫺29.6 ⫾ 2.4 to ⫺34.1 ⫾ 2.8
mmol/kg (P ⫽ 0.02). Muscle static (⌬ATP/N) and dynamic
(⌬ATP/J) costs of contraction were unaffected by creatine
supplementation as well as were ATP, Pi, pH, PCr resynthesis
rate, and muscle strength and endurance. ⌬ATP/J and ⌬ATP/N
were greatest at the onset of the exercise protocol (P ⬍ 0.01).
In summary, creatine supplementation increased muscle PCr
concentration, which did not affect muscle ATP cost of contrac-
tion.
muscle economy; phosphocreatine; skeletal muscle; magnetic
resonance spectroscopy
DIETARY CREATINE SUPPLEMENTATION (0.3 g · kg⫺1 · day⫺1
for 5 days) has been shown to increase muscle phospho-
creatine (PCr) concentration and hydrolysis (31) and
improve muscle performance during intermittent high-
intensity exercise (1, 3, 6, 14, 20–22). Although PCr
availability and use are enhanced throughout intermit-
tent exercise bouts, few studies report improvements in
performance during initial intermittent bouts or during
single bouts of exercise after supplementation (2, 11,
15, 16, 30, 32, 33, 39). A potential explanation for these
findings may be that creatine supplementation alters
the energy cost of muscle force production (ATP cost of
contraction) at the onset of exercise by increasing
muscle PCr concentration.
The ATP cost of contraction varies depending on
muscle fiber type, substrate availability, and contrac-
tion frequency and duration. Muscle ATP costs have
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116
been found to be higher at the onset of contraction (9,
31), increase as contraction frequency increases, and
decrease as contraction duration increases (4, 10, 13,
36, 37), suggesting that muscle excitation-relaxation
processes influence the ATP cost of muscle contraction.
In addition, human and animal studies have reported
that fast-twitch (type II) muscle fibers have higher PCr
concentrations and hydrolysis rates than slow-twitch
(type I) fibers (5, 28) and a greater ATP cost of contrac-
tion (8, 12, 24, 34). Conversely, a depletion of ATP and
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PCr stores in rat muscle has been shown to reduce the
cost of contraction (17, 18). These findings suggest that
there may be a positive relationship between muscle
PCr concentration and the cost of contraction. The
effect of increasing muscle PCr via creatine supplemen-
tation on the ATP cost of contraction, however, has not
been investigated. A study of this design may further
define the degree of dependence between muscle PCr
concentration and cost of contraction and assist in
determining possible mechanisms responsible for the
variations observed in muscle cost of contraction.
The purpose of this study was to determine the
effects of creatine supplementation and exercise on
skeletal muscle ATP costs of contraction by measuring
energy expenditure during brief static and dynamic
exercise bouts performed before and after exhaustive
exercise. In addition, the effects of creatine supple-
mentation on pH, phosphagen kinetics, and muscle
endurance were investigated. Intramuscular pH and
phosphagen compounds were measured noninvasively
throughout exercise and recovery by using 31P-mag-
netic resonance spectroscopy (MRS), which greatly
enhances measurement resolution over muscle biopsy
techniques (29). We hypothesized that 1) creatine
supplementation would influence muscle ATP cost of
contraction by increasing PCr availability, 2) muscle
cost of contraction would decline after exercise, and 3)
creatine supplementation would improve muscle endur-
ance. The possible association of PCr creatine supple-
mentation and cost of muscle contraction has yet to be
investigated.
METHODS
Subjects. Six women and three men participated in the
study (Table 1). All subjects were physically active, free from
chronic disease, and used no regular medications, as deter-
mined by a medical history questionnaire. The study was
approved by the appropriate institutional review boards, and
all subjects gave their voluntary and informed consent before
participation.
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 CREATINE AND COST OF CONTRACTION
Table 1. Subject characteristics
Placebo Creatine
Age, Weight, Weight,
Subjects n yr kg kg
Women 6 28 ⫾ 1.4 57.0 ⫾ 1.2 57.0 ⫾ 1.3
Men 3 33 ⫾ 2.1 68.8 ⫾ 4.8 69.0 ⫾ 5.7
Values are means ⫾ SE.
Creatine supplementation. Two single-blind exercise trials
were performed: a placebo trial, which was followed by a
creatine trial 7–14 days later. The trials were not random-
ized, as skeletal muscle creatine levels can remain elevated
above basal levels for 4–5 wk after supplementation stops
(23). Five days before each trial, the subjects began consum-
ing 0.3 g · kg⫺1 · day⫺1 of either a placebo (granulated sugar) or
0.3 g · kg⫺1 · day⫺1 of creatine monohydrate (Phosphagen, Ex-
perimental and Applied Sciences, Pacific Grove, CA) com-
bined with 0.3 g · kg⫺1 · day⫺1 of a flavored powder drink mix.
The relative creatine dosage was determined by using a mean
body weight of 70 kg at a dose of 20 g/day (22, 23). The
mixture was dissolved in water and consumed four times per
day. The subjects were blinded as to whether they were
receiving the placebo or creatine, and the mixtures were
similar in taste, texture, and color.
Exercise. Both groups performed single-leg knee-extension
exercise to exhaustion while lying supine inside a whole body
1.5-T magnetic resonance system (General Electric SIGNA,
General Electric Medical Systems, Milwaukee, WI). Exhaus-
tion was defined as the time when the subject could not
maintain the rate and/or range of motion after being given
117
verbal encouragement by the investigators. The exercise
apparatus provided concentric resistance via a lever arm-and-
pulley system integrated with a flywheel and resistance
strap, as illustrated elsewhere (35). An elastic cord returned
the lever arm to the starting position after each knee exten-
sion. Knee extensions were performed from ⬃110 to ⬃145° of
knee extension at 37 contractions/min set by an audible
metronome. Power output during exercise was determined by
measuring the velocity and tension applied to an in-line
pulley and by estimating leg mass (41). Both legs were tested
in each experimental condition.
Before the experimental trials, two to three exercise prac-
tice sessions were performed to familiarize the subjects with
the experimental procedures and to determine the appropri-
ate exercise intensity. The maximum flywheel resistance at
which each subject was able to perform 3–4 min of exercise
was used. Therefore, the resistance for each subject was
dependent on the subject’s muscle endurance capacity. Be-
tween the placebo and creatine trials, however, the resistance
was kept constant for each subject.
Before the exhaustive exercise bouts (preexercise) and at
select intervals during recovery, measurements of ATP cost of
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contraction were obtained during static or dynamic contrac-
tions. The arrows in Figs. 1 and 2 illustrate the preexercise
and recovery contraction sequence. To determine the quantity
of muscle ATP use per joule of work performed, the subjects
performed six dynamic knee extensions (⬃8 s) with their left
leg at 100 and 50 s before exhaustive exercise, at 30 s of
recovery, and every minute thereafter through 5 min of
recovery. The resistance and cadence for these brief dynamic
bouts were the same as those used during the exhaustive
Fig. 1. Results of phosphocreatine (PCr;
mmol/kg wet wt) and pH vs. time (s)
from rest, throughout exhaustive dy-
namic exercise and recovery for placebo
and creatine trials. Values are means ⫾
SE. Arrows indicate 1st data point after
a 5-s maximal voluntary contraction
(MVC) of quadriceps.
118 CREATINE AND COST OF CONTRACTION

Fig. 2. Results of PCr (mmol/kg wet

wt) and pH vs. time (s) from rest and
thoughout exhaustive dynamic exercise
and recovery for placebo and creatine
trials. Values are means ⫾ SE. Arrows
indicate 1st data point after 6 dynamic
knee extensions (⬃8 s).

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exercise bout. To determine the quantity of ATP use per
newton of force generated, the subjects performed a static 5-s
maximal voluntary contraction (MVC) with their right leg at
⬃110° of knee extension at 100 and 50 s before exhaustive
exercise, every 30 s of recovery for 2 min, and every minute
recover to 75% of the mean preexercise MVC value was
determined. The preexercise and recovery knee extensions
and MVCs were performed within a 10-s 31P-MRS sampling
period.
31P-MRS. 31P spectra were collected continuously from rest

thereafter through 5 min of recovery. In addition, the time to throughout exercise and recovery by a 1H/31P dual radio-

Fig. 3. Data from a single subject illus-

trating calculation of PCr hydrolysis
(⌬PCr) during recovery from exhaus-
tive exercise. s, Actual PCr data includ-
ing effects of intermittent exercise
bouts. k, Data points that were deleted
to obtain a modified curve representing
PCr recovery without intermittent exer-
cise illustrated by r. Dotted line repre-
sents monoexponential (monoexp) curve
fit to modified PCr data, and arrows
indicate ⌬PCr.
 CREATINE AND COST OF CONTRACTION 119

frequency transmit/receive 11-cm surface coil (USAsia, Colum- Table 2. Muscle PCr, Pi , ATP, and pH results
bus, OH) placed over the quadriceps muscles. 31P data were
acquired by using a hard-pulse 25.85-MHz excitation (pulse Recovery
width 600 µs), repetition time 1,000 ms, spectral width 2,000 Variable Trial Rest End Exercise (3 min)
Hz, and 1,024 sampled free induction decay (FID) points. PCr, mmol/kg Placebo 40.7 ⫾ 1.8 11.7 ⫾ 2.0 31.6 ⫾ 1.6
Before exercise, a proton magnetic resonance image was Creatine 46.6 ⫾ 1.1* 11.1 ⫾ 2.1 34.7 ⫾ 1.5
acquired axially by using the 1H/31P surface coil to verify coil Pi , mmol/kg Placebo 4.57 ⫾ 0.29 31.3 ⫾ 2.8 9.34 ⫾ 1.08
placement and muscle group participation. A linear gradient Creatine 4.54 ⫾ 0.19 33.4 ⫾ 2.2 9.16 ⫾ 1.09
shim procedure was performed to reduce field inhomogeneity ATP, mmol/kg Placebo 5.5 3.97 ⫾ 0.24 4.51 ⫾ 0.27
within the sensitive volume. Surface coil transmitter and Creatine 5.5 4.45 ⫾ 0.27 4.91 ⫾ 0.20
receiver gains for 31P-MRS were set once to maximize PCr pH Placebo 7.13 ⫾ 0.07 6.46 ⫾ 0.07 6.70 ⫾ 0.07
Creatine 7.12 ⫾ 0.07 6.49 ⫾ 0.07 6.45 ⫾ 0.07
signal acquired from the muscle and kept constant through-
out the study. Ten FID signals were averaged producing one Values are means ⫾ SE. Placebo and creatine trial results for
spectrum every 10 s. Care was taken to ensure that exercise phosphocreatine (PCr), Pi , ATP, and pH for subjects’ right and left
began and ended at the onset of an FID cycle. The magnetic quadriceps at rest, at the end of exhaustive exercise, and after 3 min
resonance system was calibrated by using known standards of recovery. There were no differences or interactions with regard to
leg, as indicated by repeated-measures ANOVA. * Significant differ-
on each testing day.
ence from corresponding placebo value (P ⫽ 0.03).
FID processing consisted of apodization of 10-Hz line
broadening, zero-filling to 4,096 points and Fourier transfor-
mation, followed by zero- and first-order phasing. Relative per joule of work produced (⌬ATP/J; mmol · kg⫺1 · J⫺1 ) for the
concentrations of Pi, PCr, and ␤ATP were determined from brief dynamic bouts. During the final 10 s of exhaustive
spectral peak areas. PCr/␤ATPrest, Pi/␤ATPrest, and ␤ATP/ dynamic exercise, ATP cost of contraction was determined by
␤ATPrest ratios were converted to millimoles per kilogram wet calculating ATP use derived from PCr, glycolysis, and oxida-

Downloaded from jap.physiology.org on May 24, 2011

weight by assuming that the area of ␤ATPrest was equivalent
to 5.5 mmol⫺1 · kg wet wt⫺1 (37). ␤ATPrest was the mean area of
the two initial resting ␤ATP peaks. Finally, pH was calculated
by using the chemical shift between the Pi and PCr frequency
(38).
The rate of PCr resynthesis and a time constant (Tc) were
determined from a monoexponential curve fit to the PCr
recovery data after exhaustive exercise (25–27, 40). The
following monoexponential equation was used: y ⫽ a[1 ⫺
exp(bx)] ⫹ c, where y represents the PCr value at any given
time x, a is the change in PCr during recovery, b is the rate
constant (1/b ⫽ Tc), and c is the initial PCr value at the onset
of recovery. The values for initial PCr resynthesis rate were
determined from the slope of the initial 10 s of the monoexpo-
nential curve fit (24, 38). Before fitting, the PCr data were
modified, eliminating two data points after each knee exten-
sion or MVC bout during recovery, as indicated by r in Fig. 3.
A pilot study determined that this procedure provided recov-
ery curves comparable to curves obtained without intermit-
tent dynamic and static exercise (n ⫽ 4, r ⫽ 0.92, P ⬍ 0.01).
The quantity of PCr hydrolysis (⌬PCr) was determined for
preexercise and recovery contractions. To account for the
ongoing resynthesis of PCr during recovery, the quantity of
PCr resynthesized during each brief bout was derived from
the monoexponential curve and added to the actual change in
PCr to determine the total ⌬PCr, as illustrated in Fig. 3. For
each subsequent dynamic and static bout, the monoexponen-
tial curve was shifted 20 s to the right, and ⌬PCr was
calculated. The total PCr hydrolysis during the exhaustive
exercise bout was determined as the change in PCr from rest
to the end of exhaustive exercise.
ATP cost of contraction during the brief static and dynamic
bouts was determined by calculating ATP use derived from
PCr hydrolysis (7, 31) and by measuring the force or work
produced during the contractions. For bouts of ⬍10 s, the
change in PCr has been shown to accurately reflect ATP use
(19). Potential production of ATP from anaerobic glycolysis
was monitored via the changes in muscle pH (31), and
mitochondrial oxidative phosphorylation has been shown to
be delayed ⬃10 s from the onset of exercise (7, 19). The ATP
cost of contraction was represented as the millimoles per
kilogram of ATP used per newtons of force produced multi-
plied by seconds (⌬ATP/N; mmol · kg⫺1 · N · s⫺1 ) for the brief
static bouts and as the millimoles per kilogram of ATP used
tive phosphorylation (31).
Analysis. For variables pertaining to the exhaustive exer-
cise bouts (⌬PCr, initial PCr resynthesis rate, Tc, mean power
output, and time to exhaustion), repeated-measures ANOVA
tests were used with treatment (creatine vs. placebo) and leg
(right vs. left) as factors. For variables pertaining to the
preexercise and recovery dynamic and static contractions
(PCr, Pi, ATP, ⌬ATP/N, ⌬ATP/J, and peak MVC), repeated-
measures ANOVA tests were used with treatment (creatine
vs. placebo) and time (preexercise and recovery bouts) as
factors. Newman-Keuls post hoc tests were used to determine
mean differences between and within factors. A paired t-test
was used to determine mean differences in body weight and
time to 75% MVC recovery between the placebo and creatine
trials. The significance level was set at P ⬍ 0.05 for all tests,
and results are presented as means ⫾ SE.
RESULTS
Creatine supplementation. Figures 1 and 2 illustrate
the relationship between PCr and pH kinetics during
the placebo and creatine trials for the static (5-s MVCs)
and dynamic (6 extensions) exercise protocols. Tables 2
and 3 contain phosphagen kinetic and muscle perfor-
mance results obtained during exhaustive exercise and
Table 3. Muscle performance and PCr
metabolic results
Variable Placebo Creatine P Value
Mean power, W 17.9 ⫾ 0.5 18.0 ⫾ 0.5 0.98
⌬PCr, mmol/kg wet wt ⫺29.6 ⫾ 2.4 ⫺34.1 ⫾ 2.8 0.02
PCrrate , mmol · kg⫺1 · min⫺1 27.0 ⫾ 1.8 32.1 ⫾ 2.0 0.19
Tc, s 49.1 ⫾ 3.6 46.6 ⫾ 3.7 0.66
Time to exhaustion, s 268 ⫾ 17 286 ⫾ 20 0.25
Time to 75% MVC recovery, s 63.3 ⫾ 17.6 82.5 ⫾ 25.8 0.71
Values are means ⫾ SE. Results for mean power output during
exhaustive exercise, PCr hydrolysis (⌬PCr), initial PCr resynthesis
rate (PCrrate ; mmol · kg wet wt⫺1 · min⫺1 ), PCr resynthesis time
constant (Tc), time to exhaustion, and time to 75% maximal volun-
tary contraction (MVC) recovery for placebo and creatine trials. Data
from both quadriceps were included. There were no differences or
interactions with regard to leg, as indicated by repeated-measures
ANOVA.
120 CREATINE AND COST OF CONTRACTION
Fig. 4. ATP cost of contraction per N · s
of force produced (⌬ATP/N; mmol · kg
wet wt⫺1 · N · s⫺1 ) for 5-s MVC bouts
performed before (preexercise) exhaus-
tive exercise and during recovery. Val-
ues are means ⫾ SE. * Significant differ-
ence from preexercise ⫺100-s bout for
placebo and creatine results (P ⬍ 0.01).
include bilateral data for each subject. There were no
differences or interactions with regard to right vs. left
leg for any of these results, as indicated by the repeated-
measures ANOVA. After creatine supplementation, rest-
ing muscle PCr was increased by 15% (P ⫽ 0.04, Table
2), and total PCr hydrolysis during the exhaustive
exercise bout was increased by 13% (P ⫽ 0.02, Table 3)
while the mean exercise power output remained con-
stant (Table 3). During recovery, the initial PCr resyn-
thesis rate and Tc were not significantly affected by
creatine (Table 3). ATP levels declined during exercise
(P ⬍ 0.01) and tended to be greater overall after
creatine supplementation (P ⫽ 0.08); however, there
were no interactions between time and treatment fac-
tors (Table 2). There were no differences in Pi and pH
kinetics after creatine supplementation (Table 2). There
was, however, a consistent increase in pH and reduc-
tion in PCr values (P ⬍ 0.01) as a result of the static and
dynamic bouts performed during preexercise and recov-
ery, as illustrated in Figs. 1 and 2. The duration of
recovery data collection varied depending on each
subject’s time to exhaustion. After 180 s of recovery, the
subject number represented by the data begins to
decline, which causes some fluctuation in the PCr and
pH recovery data in Figs. 1 and 2.
Figures 4 and 5 illustrate the static, ⌬ATP/N, and
dynamic, ⌬ATP/J, ATP costs of contraction during
preexercise and recovery for the placebo and creatine
trials. Neither ⌬ATP/N nor ⌬ATP/J was significantly
affected by creatine supplementation (P ⫽ 0.98). ATP
was derived from PCr hydrolysis during preexercise,
initial 10 s of exhaustive exercise, and recovery. Measur-
able contributions from glycolysis and oxidative phos-
Fig. 5. ATP cost of contraction per J of
work produced (⌬ATP/J; mmol · kg wet
wt⫺1 · J⫺1 ) for bouts of 6 dynamic knee
extensions performed before (preexer-
cise) exhaustive exercise and during
recovery. Values are means ⫾ SE. * Sig-
nificant difference from preexercise
⫺100-s bout for placebo and creatine
results (P ⬍ 0.01).
phorylation were not detected, which is consistent with
previous studies (7, 19). In contrast, most of the ATP
(⬎95%) utilized during the final 10 s of exhaustive
exercise (Fig. 6) was derived from oxidative phosphory-
lation. The ATP cost of contraction calculated at the end
of exhaustive exercise (Fig. 6) was not different from
ATP costs calculated during dynamic recovery derived
Downloaded from jap.physiology.org on May 24, 2011
from ⌬PCr (Fig. 5). Creatine supplementation, how-
ever, increased the ATP cost of contraction during the
final 10 s of exhaustive exercise compared with the
placebo value (Fig. 6).
The indicators of muscle performance, time to exhaus-
tion, time to 75% MVC recovery, and peak MVC,
illustrated in Table 2 and Fig. 7, were not significantly
influenced by creatine supplementation. All the sub-
jects were verbally encouraged by the investigators
during exercise and appeared to give their maximal
effort. The work performed during the preexercise and
recovery six extension dynamic bouts (not shown) was
consistent throughout both trials.
Exhaustive exercise. The ATP cost of contraction for
the brief static and dynamic bouts declines after the
initial preexercise bout. The initial preexercise ⌬ATP/N
value at ⫺100 s was greater than the recovery values
for 30 through 240 s (P ⬍ 0.01, Fig. 4). Similarly, the
initial preexercise ⌬ATP/J at ⫺100 s was greater than
the preexercise ⫺50 s value and all the ⌬ATP/J recov-
ery values (P ⬍ 0.01, Fig. 5). These results indicate that
during the initial brief dynamic and static exercise
bouts the quadriceps muscles had a higher ATP cost of
contraction compared with subsequent ATP costs mea-
sured during preexercise and during recovery from
exhaustive exercise.
 CREATINE AND COST OF CONTRACTION
Fig. 6. ⌬ATP/J (mmol · kg wet wt⫺1 · J⫺1 ) during initial 10 s and final
10 s of exhaustive exercise. Values are means ⫾ SE. * Significant
difference from corresponding placebo value (P ⫽ 0.03).
DISCUSSION
This study investigated the effects of oral creatine
supplementation and exhaustive exercise on muscle
ATP cost of contraction. In addition, the effects of
creatine supplementation on muscle phosphagen me-
tabolism, pH, and endurance were examined. 31P-MRS
was used to measure quadriceps muscle PCr, Pi, ATP,
and pH throughout exercise and recovery during a
placebo and creatine trial. Muscle ATP cost of contrac-
tion was measured during 5-s static and ⬃8-s dynamic
exercise bouts performed before and after exhaustive
exercise and derived from the ⌬ATP and force output of
the muscle. The brief static and dynamic bouts were
used to minimize ATP production by glycolytic and
oxidative systems, so that PCr hydrolysis would reflect
ATP use by contracting muscle fibers (7, 19). We
hypothesized that 1) creatine supplementation would
increase muscle ATP cost of contraction by increasing
PCr availability and utilization, 2) the muscle cost of
contraction would be reduced after exhaustive exercise,
and 3) creatine supplementation would improve muscle
performance.
Creatine supplementation. Our results show a 15%
increase in resting muscle PCr and a 13% increase in
total PCr hydrolysis during exhaustive exercise after
121
creatine supplementation (Tables 2 and 3), which is
consistent with previous results (35). However, the
increase in PCr availability and overall use brought
about by creatine supplementation did not affect muscle
ATP cost of contraction calculated from brief static and
dynamic exercise bouts (Figs. 4 and 5). Studies have
reported that fast-twitch muscle fibers have greater
resting PCr levels, PCr hydrolysis rates, and ATP cost
of contraction than slow-twitch fibers (5, 8, 12, 24, 28,
34). Conversely, a depletion of ATP and PCr stores in
rat muscle by hadacidin, an adenylosuccinate synthase
inhibitor, has been shown to reduce the cost of contrac-
tion (17, 18). Furthermore, PCr levels and ATP cost of
contraction differ widely among individuals (8). Given
that no change was observed in ATP cost of contraction
after creatine supplementation, our results suggest
that PCr availability and utilization do not appear to be
associated with differences in ATP cost of contraction
observed across muscle fiber types and individuals.
Other factors, such as cross-bridge cycling rate and cost
of excitation and relaxation processes, inherent to
Downloaded from jap.physiology.org on May 24, 2011
muscle fiber types, most likely account for the differ-
ences observed in the cost of contraction.
Creatine supplementation increased ATP costs of
contraction in the last 10 s of exhaustive dynamic
exercise (Fig. 6). However, ATP hydrolysis during this
10-s period was predicted primarily from the initial
PCr resynthesis rate during recovery, which was found
to be increased by creatine supplementation in middle-
aged persons (35). Although the initial PCr resynthesis
rate was not significantly influenced by creatine supple-
mentation in this study (Table 3), nonsignificant in-
creases in PCr resynthesis rate may account for the
difference in ATP cost of contraction. This raises some
question as to the validity of using PCr resynthesis rate
to predict ATP production from oxidative phosphoryla-
tion when muscle creatine is manipulated by creatine
supplementation. That is, the change in ATP produc-
tion after creatine supplementation calculated from the
PCr resynthesis rate may have resulted from changes
in PCr recovery kinetics, not from changes in mitochon-
drial oxidative capacity, as the calculation was in-
tended to measure (9, 31). Further study is required to
elucidate the relationship between changes in PCr
concentration after creatine supplementation and PCr
resynthesis rate.
Fig. 7. Peak MVC force (N) for bouts
performed before (preexercise) exhaus-
tive exercise and during recovery. Val-
ues are means ⫾ SE. * Significant differ-
ence from preexercise ⫺100-s bout for
placebo and creatine results (P ⬍ 0.01).
122 CREATINE AND COST OF CONTRACTION
Creatine supplementation tended to spare ATP stores
(P ⫽ 0.08, Table 2) during exhaustive exercise, which is
consistent with previously reported trends (3, 16).
However, the muscle performance indicators, peak
MVC force (Fig. 7), time to exhaustion, and time to 75%
MVC recovery (Table 3) were not significantly influ-
enced. Although creatine supplementation increased
PCr concentration by 15%, one-half of the total PCr
hydrolyzed during the ⬃277-s exhaustive exercise bouts
was consumed in the first 30 s (Figs. 1 and 2), indicat-
ing that muscle ATP requirements were supplied pri-
marily from glycolytic and oxidative systems. While
studies have shown that creatine supplementation
improves brief intermittent exercise performance (1, 3,
6, 14, 20–22), most findings indicate that creatine does
not significantly improve single-bout exercise perfor-
mances as in this study (2, 11, 15, 16, 30, 32, 33, 39).
Exhaustive exercise. Figures 4 and 5 illustrate that
the ATP cost of contraction for brief static (i.e., ⌬ATP/N)
and dynamic (i.e., ⌬ATP/J) exercise declined after the
initial bout at ⫺100 s preexercise and was less after
exhaustive exercise. Our results are consistent with
studies in which ATP cost of contraction during continu-
ous and intermittent static contractions of the gastroc-
nemius/soleus muscles was reported to decline after the
onset of a contraction sequence (9, 31). In addition,
studies comparing static intermittent and continuous
exercise of the quadriceps muscles report higher ATP
cost of contraction and fatigue rates during intermit-
tent vs. continuous contractions (4, 10, 37). The results
of these studies and ours suggest that changes in ATP
use by excitation/relaxation mechanisms during the
course of exercise may account for the differences in
ATP cost of contraction.
During muscle contraction, there are several sites of
ATP utilization, actomyosin cross bridges, Ca2⫹ pumps,
Na⫹-K⫹ pumps, and phosphorylation processes that
may influence the cost of contraction during the preex-
ercise bouts. At the onset of exercise, the Ca2⫹ flux
across the sarcoplasmic membrane is greater than that
during continuous exercise, which increases Ca2⫹ pump
ATP consumption and has been suggested as a mecha-
nism for the increased cost of contraction at the onset of
exercise (4, 10, 37). In addition, the cross-bridge turn-
over rate, particularly for fast-twitch muscles, appears
to be greater at the onset of a contraction, leading to a
higher initial ATP consumption (8, 10, 24). It has been
estimated that the total ATP costs for a 1-s quadriceps
muscle contraction is 60% greater than the ATP cost
during continuous contraction (4).
It has also been suggested that the higher ATP cost at
the onset of exercise may be a result of underestimation
of ATP costs later in exercise, when ATP for contraction
is supplied predominantly from glycolytic and oxidative
energy stores (9). In this study, the brief (⬍10 s)
preexercise and recovery bouts were used to minimize
the muscle ATP consumption from glycolytic and oxida-
tive energy stores. Given the intensity and duration of
these bouts, the ⌬PCr should accurately predict ATP
consumption by the muscle (7, 19). The pH values
during preexercise and recovery increase after each
bout, indicating H⫹ consumption by the creatine kinase
reaction. Significant ATP generation by anaerobic gly-
colysis should mask this effect. Activation of oxidative
phosphorylation has been shown to be delayed ⬃10 s
from the onset of exercise (7, 19). Furthermore, there is
consistency between cost of contraction values derived
from ⌬PCr at 30 s of recovery (Fig. 5) and values
derived primarily from oxidative phosphorylation at
the end of exhaustive exercise (Fig. 6).
Conclusion. This study investigated the effects of
creatine supplementation and exhaustive exercise on
ATP cost of contraction and the effects of creatine
supplementation on muscle endurance and phospha-
gen metabolism. Quadriceps muscle pH and phospha-
gen kinetics were measured by using 31P-MRS. The
ATP cost of contractions was determined by measuring
⌬ATP and force production during brief dynamic and
static contractions performed at select intervals before
and after exhaustive exercise.
Creatine supplementation increased muscle PCr con-
centration; however, this did not affect muscle ATP cost
Downloaded from jap.physiology.org on May 24, 2011
of contraction, as we hypothesized. These results sug-
gest that differences in ATP cost of contraction observed
between individuals (7) and muscle fiber types (5, 12,
24, 28, 34) are unaffected by increases in PCr availabil-
ity resulting from creatine supplementation. In addi-
tion, muscle performance, as determined by time to
exhaustion, time to 75% MVC recovery, and peak MVC,
was not significantly affected by creatine supplementa-
tion. The ATP cost of contraction for both conditions
was greatest at the onset of exercise. These results are
consistent with previous studies (9, 31) and suggest
that the increased ATP cost of contraction at the onset
of exercise is associated with muscle excitation and
relaxation processes.
The views, opinions, and/or findings contained in this report are
those of the authors and should not be construed as an official
Department of the Army position, policy, or decision.
This research was supported in part by a Dudley Allen Sargent
Research Fund grant from the Sargent College of Health and
Rehabilitation Sciences, Boston University, Boston, MA. R. A. Field-
ing is a Brookdale National Fellow at Boston University.
Address for reprint requests: S. A. Smith, Belmont Univ., 1900
Belmont Blvd., Nashville, TN 37212-3757 (E-mail: smiths@mail.
belmont.edu).
Received 18 November 1998; accepted in final form 17 March 1999.
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