Creatine and Creatinine Metabolism - Physiological Reviews

July 2000 CREATINE AND CREATININE METABOLISM 1179
water retention in the initial days of Cr supplementation
(387, 442). Because the proportion of fat tended to decrease
and lean tissue weight increased with Cr supplementation
(209, 312, 510, 511, 952, 1040), the increase in
body weight most likely reflects a corresponding increase
in actual muscle mass and/or volume, a point that is
particularly relevant for bodybuilders.
Because the contribution of PCr hydrolysis to ATP
regeneration is expected to be most relevant in (supra-)
maximal exercise, in particular at the time when [PCr]
normally becomes limiting (365, 386), a favorable effect of
Cr supplementation on muscle performance is most likely
in short-term high-intensity exercise. On the other hand, it
is less evident how Cr supplementation should improve
endurance performance. In fact, a variety of studies have
shown an improvement in muscle performance upon Cr
supplementation mostly in high-intensity, short-duration,
repetitive exercise tests, but to some extent also in exercise
tests of intermediate duration of 30–300 s (for reviews,
see Refs. 441, 1106; see also Refs. 1, 225, 336, 583,
627, 911, 913, 952, 1038, 1041). In series of 10 repeated 6-s
bouts of high-intensity exercise on a cycle ergometer
interspersed with 30-s passive rest periods, subjects were
better able to maintain a pedal speed of 140 rev/min after
a 6-day period of Cr supplementation (30 g/day) than after
placebo ingestion (Fig. 19) (44). In a protocol of 6 � 6sof
repeated cycle sprints departing every 30 s, Cr supplementation
(20 g/day over 5 days) significantly increased
total work completed over the six sprints, work performed
in sprint 1, as well as peak power (162). In a
series of two or three 30-s bouts of maximal isokinetic
FIG. 19. Effect of Cr supplementation on muscle performance in 10
6-s bouts of high-intensity cycling at an intended frequency of 140
rev/min. Mean rev/min for the interval 4–6 s of each individual exercise
bout are shown before (�) and after (■) 6 days of Cr supplementation.
[Modified from Balsom et al. (44).]
cycling, separated by 4 min of recovery, Cr ingestion at a
rate of 20 g/day for 5 days significantly increased peak and
mean power output in exercise bout 1 as well as total
work output in bouts 1 and 2, all by 4–8% (66, 113). The
increases in both peak and total work production over the
two exercise bouts in the study of Casey et al. (113) were
positively correlated with the increase in muscle concentration
of Cr plus PCr. Cr supplementation (20 g/day for 5
days) increased the performance in a maximal continuous
jumping test by 7% during the first 15 s and by 12% during
the second 15 s (84). In the same study, Cr supplementation
also improved the time of intensive running up to
exhaustion in an all-out treadmill run lasting �60sby
13%. Similarly, time to exhaustion of the leg at 80, 60, 40,
and 20% of the maximum voluntary force of contraction
(lasting �20–160 s) was significantly increased in resistance
trained subjects by Cr supplementation (10 g/day
for 5 days); in addition, Cr supplementation increased
maximum voluntary force of contraction by �10% (583).
In a study on a limited number of weight-trained subjects,
performance in the Wingate bike test was improved 15–
23% (209). Muscular strength, as evaluated by a one repetition
maximum (1 RM) free weight bench press test,
was increased 6.5%, and the number of lifting repetitions
at 70% of the respective 1 RM load even by 35%. Body
weight and calculated fat free mass were significantly
increased by Cr supplementation in these weight-trained
athletes despite a significantly lower daily energy, carbohydrate,
and fat intake. No explanation is currently available
for this latter finding. In resistance-trained men, Cr
supplementation (25 g/day for 6 days) resulted in a significant
increase in muscle performance during multiple sets
of bench press (higher number of repetitions until exhaustion
at 10 RM) or jump squat exercise (increased peak
power output) (1068). In a protocol involving three interval
series of 3 � 30, 4 � 20, and 5 � 10 maximal voluntary
contractions of the knee extensors on an isokinetic dynamometer,
with rest intervals of 2 min between series and
20–60 s between individual bouts, dynamic torque production
was increased 10–23% after 6 days of Cr ingestion
(0.5 g � kg �1 � day �1 ) (1039). This ergogenic action of Cr
was, however, completely abolished by simultaneous caffeine
intake, even though caffeine had no effect on the
stimulation of Cr accumulation into muscle in response to
Cr supplementation. In trials of 4 � 300-m or 4 � 1,000-m
runs with 3- and 4-min rest intervals between repetitions,
Cr supplementation (30 g/day for 6 days) significantly
reduced the running times for the final 300-m or 1,000-m
runs as well as the total time for 4 � 1,000 m (339). Best
300-m and 1,000-m times in this series decreased significantly
by 0.3 � 0.1 and 2.1 � 0.6 s, respectively. Cr
supplementation (20 g/day for 5 days) significantly increased
the work performed in three maximal kayak ergometer
tests of 90-, 150-, and 300-s duration by 7–16%
while having no effect on peak power (627). Finally, Cr