during two bouts of maximal exercise (each
lasting 30 s) following creatine ingestion plotted
against the increase in muscle total creatine as a
result of supplementation in the same eight sub-
jects. The positive relationship found (r=0.71,P<
0.05) led to the conclusion that it may be neces-
sary to increase muscle total creatine concentra-
tion by close to or more than 20 mmol · kg–1d.m.
to obtain substantial improvements in exercise
performance as a result of creatine supplementa-
tion. These findings may provide some insight to
those studies which have reported no improve-
ment in exercise performance following creatine
supplementation. In this context, the combina-
tion of results from several recent studies under-
taken in the author ’s laboratory has revealed that
approximately 20–30% of individuals ‘do not
respond’ to creatine supplementation, i.e. they
demonstrate an increase of less than 10 mmol ·
kg–1d.m. (8%) in muscle total creatine following
5 days of 20 g · day–1oral creatine supplementa-
tion (4¥5 g doses dissolved in ª250 ml). Thus, as
suggested previously, to gain ‘optimal’ func-
tional and metabolic benefits from creatine sup-
plementation, recent data indicate that it is
important to consume creatine in combination
with a carbohydrate solution (Green et al. 1996a,
1996b).
Mechanism of action of dietary
creatine supplementation on
exercise performance
As previously stated, the literature indicates that
if the muscle creatine concentration can be
increased by close to or more than 20 mmol · kg–1
d.m. as a result of acute creatine ingestion, then
performance during single and repeated bouts of
maximal short-duration exercise will be signifi-
cantly improved. However, the exact mechanism
by which this improvement in exercise perfor-
mance is achieved is not yet clear. The available
data indicate that it may be related to the stimula-
tory effect that creatine ingestion has upon pre-
exercise PCr availability, particularly in
fast-twitch muscle fibres (Casey et al. 1996b). For
example, in the study of Casey et al. (1996b), the
increase in resting type II muscle fibre PCr con-
centration as a consequence of creatine supple-
mentation in a group of eight male subjects was
positively correlated with the increase in PCr
degradation measured during exercise in this
fibre type (r=0.78,P<0.01) and with the increase
in total work production observed during
exercise following supplementation (r=0.66,P<
0.05). No such associations were found in the
type I fibres (r=0.22 and r=0.32, respectively).
Given that PCr availability in type II fibres is gen-
erally accepted to limit exercise capacity during
maximal exercise (Hultman et al. 1991; Casey et
al.1996a), the increase in type II muscle fibre PCr
concentration as a consequence of creatine sup-
plementation may have improved contractile
function during exercise by maintaining ATP
turnover in this fibre type. This suggestion is
supported by reports showing that the accumu-
lation of plasma ammonia and hypoxanthine are
reduced during maximal exercise following crea-
tine ingestion (both metabolites are accepted
plasma markers of the disruption of muscle ATP
resynthesis), despite a higher work output
being achieved (Balsom et al. 1993a; Greenhaff et
al.1993). Furthermore, more direct supportive
evidence comes from a recent study showing that
creatine supplementation reduced the decline in
muscle ATP by approximately 30% during
maximal isokinetic cycling exercise, while, at the
same time, increasing work output (Casey et al.
1996b).
It should be recognized, however, that the
positive effects of creatine supplementation on
muscle energy metabolism and function are also
likely to be the result of the stimulatory effect
that an increase in cytoplasmic free creatine will
have on mitochondrial mediated PCr resynthesis
(Greenhaff et al. 1994), which will be particularly
important during repeated bouts of maximal
exercise. This suggestion is supported by in vitro
studies showing that an increase in the creatine
concentration of an incubation medium can
accelerate the rate of respiration in isolated skele-
tal muscle mitochondria (Bessman & Fonyo
1966) and skinned cardiac fibres (Field et al.
1994), and by in vivohuman studies showing that