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OBJECTIVE: To examine the effects of oral creatine (Cr) monohydrate supplementation on muscle Cr concentration, body mass, and total body water (TBW), extracellular water (ECW), and intracellular water (ICW) volumes. DESIGN AND SETTING: After an overnight fast, urinary Cr and creatinine concentrations, muscle Cr concentration, body mass, TBW, ECW, and ICW were measured, and subjects were randomly assigned to either a Cr or a placebo (P) group. The Cr group ingested 25 g/d of Cr for 7 days (loading phase) and 5 g/d for the remaining 21 days (maintenance phase), whereas the P group ingested a sucrose P using the same protocol. All the measures were reassessed immediately after the loading and maintenance phases. SUBJECTS: Sixteen men (age = 22.8 +/- 3.01 years, height = 179.8 +/- 7.1 cm, body mass = 84.8 +/- 11.2 kg) and 16 women (age = 21.8 +/- 2.51 years, height = 163.4 +/- 5.9 cm, body mass = 63.6 +/- 14.0 kg) involved in resistance training volunteered to participate in this study. MEASUREMENTS: Muscle Cr concentration was determined from the vastus lateralis muscle using a percutaneous needle-biopsy technique. Total body water, ECW, and ICW volumes were assessed using deuterium oxide and sodium bromide dilution analyses. RESULTS: The Cr group experienced a significant increase in muscle Cr concentration, body mass, and TBW. The P group experienced a small but significant increase in TBW only. CONCLUSIONS: The Cr supplementation protocol was effective for increasing muscle Cr concentrations, body mass, and TBW; however, fluid distribution was not changed.
44 Volume 38
Number 1
March 2003
Journal of Athletic Training 2003;38(1):44–50
q by the National Athletic Trainers’ Association, Inc
Creatine Supplementation Increases
Total Body Water Without Altering
Fluid Distribution
Michael E. Powers*; Brent L. Arnold†; Arthur L. Weltman‡; David H. Perrin§;
Dilawaar Mistry‡; David M. Kahler‡; William Kraemer\; Jeff Volek\
*University of Florida, Gainesville, FL; †Virginia Commonwealth University, Richmond, VA; ‡University of Virginia,
Charlottesville, VA; §University of North Carolina at Greensboro, Greensboro, NC; \University of Connecticut,
Storrs, CT
Michael E. Powers, PhD, ATC, CSCS, contributed to conception and design; acquisition and analysis and interpretation of the
data; and drafting, critical revision, and final approval of the article. Brent L. Arnold, PhD, ATC, contributed to conception and
design; analysis and interpretation of the data; and drafting, critical revision, and final approval of the article. Arthur L.
Weltman, PhD, and David H. Perrin, PhD, ATC, contributed to conception and design and drafting and final approval of the
article. Dilaawar Mistry, MD, ATC, and David M. Kahler, MD, contributed to acquisition of the data and drafting and final
approval of the article. William Kraemer, PhD, contributed to conception and design; analysis and interpretation of the data;
and drafting and final approval of the article. Jeff Volek, PhD, contributed to analysis and interpretation of the data and drafting
and final approval of the article.
Address correspondence to Michael E. Powers, PhD, ATC, CSCS, 144 FL Gym, PO Box 118205, Gainesville, FL 32611-8205.
Address e-mail to
To examine the effects of oral creatine (Cr) mono-
hydrate supplementation on muscle Cr concentration, body
mass, and total body water (TBW), extracellular water (ECW),
and intracellular water (ICW) volumes.
Design and Setting:
After an overnight fast, urinary Cr and
creatinine concentrations, muscle Cr concentration, body mass,
TBW, ECW, and ICW were measured, and subjects were ran-
domly assigned to either a Cr or a placebo (P) group. The Cr
group ingested 25 g/d of Cr for 7 days (loading phase) and 5
g/d for the remaining 21 days (maintenance phase), whereas
the P group ingested a sucrose P using the same protocol. All
the measures were reassessed immediately after the loading
and maintenance phases.
Sixteen men (age 5 22.8 6 3.01 years, height 5
179.8 6 7.1 cm, body mass 5 84.8 6 11.2 kg) and 16 women
(age 5 21.8 6 2.51 years, height 5 163.4 6 5.9 cm, body mass
5 63.6 6 14.0 kg) involved in resistance training volunteered
to participate in this study.
Muscle Cr concentration was determined
from the vastus lateralis muscle using a percutaneous needle-
biopsy technique. Total body water, ECW, and ICW volumes
were assessed using deuterium oxide and sodium bromide di-
lution analyses.
The Cr group experienced a significant increase in
muscle Cr concentration, body mass, and TBW. The P group
experienced a small but significant increase in TBW only.
The Cr supplementation protocol was effective
for increasing muscle Cr concentrations, body mass, and TBW;
however, fluid distribution was not changed.
Key Words:
ergogenic aids, hydration, fluid balance, body
mass, body composition
reatine (Cr) supplementation continues to be extremely
popular as a potential ergogenic aid among athletes at
all levels. Studies have shown that muscle Cr and phos-
phocreatine can be significantly elevated when a normal diet
is supplemented with Cr.
The theory behind its use is sim-
ilar to that of carbohydrate loading, because an increased mus-
cle Cr content would conceivably enhance the capacity of the
phosphagen energy system, providing greater resistance to fa-
tigue and improving performance. Anecdotal reports of ergo-
genic value have been supported by scientifically controlled
studies investigating its effects on strength,
and fatigue.
However, not all the findings sup-
port ergogenic claims.
Numerous anecdotal reports have associated muscle cramp-
ing, spasm, strains, gastrointestinal distress, kidney dysfunc-
tion, and heat illness with Cr supplementation. At this time,
however, the only side effect directly associated with Cr sup-
plementation is weight gain.
Some of these au-
thors have reported increases in body mass after only a loading
phase of supplementation (20–25 g/d for 5–7 days).
Thus, it is likely that the gains are due more to greater water
retention during supplementation than to lean-tissue accretion.
It is conceivable that increased muscle Cr concentrations are
associated with changes in the intracellular osmotic pressure,
resulting in movement of water into the cell, water retention,
and weight gain. When water loss through sweating occurs
from exercise, increased environmental temperatures, or a
combination of both, this intracellular fluid shift may be det-
rimental. For example, the water bound inside the cell may
not be available to the extracellular compartment for thermal
regulation. Therefore, cramping and other heat-related prob-
lems may result from a fluid shift occurring during supple-
Journal of Athletic Training 45
mentation. However, the existence of this Cr-related fluid shift
is speculative because only 1 group
to date has reported
changes in fluid distribution after supplementation. It must be
noted that fluid volumes were not measured directly in that
study but were predicted using a bioelectric impedance anal-
ysis. Furthermore, muscle Cr was not assessed, so whether the
changes in fluid distribution were actually associated with an
increased muscle Cr concentration is unknown. Therefore, the
purpose of this study was to investigate the effects of Cr sup-
plementation on muscle Cr concentration and fluid distribution
using a direct measure of fluid volumes.
Sixteen men (age 5 22.8 6 3.01 years, height 5 179.8 6
7.1 cm, body mass 5 84.8 6 11.2 kg) and 16 women (age 5
21.8 6 2.51 years, height 5 163.4 6 5.9 cm, body mass 5
63.6 6 14.0 kg) who were involved in a total-body resistance
training program for at least 3 days per week were randomly
assigned to either a Cr supplementation group or a placebo
(P) group. We excluded subjects from participation if they had
supplemented their habitual diet with any form of Cr during
the past 60 days; were suffering from any form of kidney,
liver, or endocrine disease or any disorder that might affect
normal cellular levels of Cr or fluid balance (or both); or were
taking any substance classified as a diuretic other than the
caffeine found in their habitual diet. We also excluded women
who were currently using oral contraceptives and women who
had not completed 2 menstrual cycles since last using oral
contraceptives. Before participating, each subject read a de-
scription of the study and signed an informed consent form
approved by the university’s institutional review board, which
also approved the study.
The evening before the supplementation period began, each
subject reported to the university’s General Clinical Research
Center for an overnight stay and for baseline measurements.
We instructed the subjects to refrain from any type of exercise
after the last meal of the day before being admitted for the
overnight stay. To control for changes in fluid distribution
across the menstrual cycle, each woman began the study be-
tween days 1 and 7 of the cycle. Upon arrival at the Center,
venous blood and urine samples were taken for a complete
clinical chemistry panel (20 items) and for drugs of abuse,
anabolic steroid, and pregnancy screen. After an overnight
fast, we measured each subject for body mass, urinary Cr and
creatinine concentrations, total body water (TBW) content, ex-
tracellular water (ECW) content, and muscle Cr concentration.
Once these measurements were completed, the supplementa-
tion period began. We instructed the subjects to maintain their
normal diets and their regular resistance-training programs
throughout the entire supplementation and testing period. We
also instructed the subjects to refrain from ingesting any type
of nonsteroidal anti-inflammatory medication, nutritional sup-
plement, or substance classified as a diuretic other than the
caffeine found in the habitual diet. Each subject was required
to maintain a training log in which the number of sets, repe-
titions, and the resistance used were recorded during each ex-
ercise session. Additionally, we asked each subject to complete
a weekly questionnaire designed to determine the incidence of
any adverse effects during supplementation. All subjects re-
ported back to the Center on the evening of the seventh and
28th (final) day of supplementation, at which time the over-
night fast and subsequent measurements were repeated.
We randomly assigned each subject to either a Cr supple-
mentation group or a P group in a double-blind fashion. Sub-
jects in the Cr group (8 men, 8 women) ingested 5.0 g of
Phosphagen (Experimental and Applied Sciences, Inc, Golden,
CO) mixed with 15 g of a flavored simple carbohydrate 5
times per day for 7 days (loading phase). Immediately after
the loading phase, each subject ingested the same supplement
once a day for the remaining 21 days (maintenance phase).
Subjects in the P group (8 men, 8 women) ingested 20 g of
the flavored simple carbohydrate for 28 days using the same
protocol as the Cr group. Individual-dose packages, identical
in weight, were prepared for the Cr and the P groups and
dispensed weekly. We instructed the subjects to mix the pow-
der supplement with 16 oz (0.47 L) of water and maintain a
daily record of the supplementation times. Finally, to further
monitor compliance, we asked each subject to return any un-
used portions at the end of each week.
Urinary Creatine and Creatinine. Urine samples were
collected and frozen at 2808C for later analysis of Cr and
creatinine concentrations using high-performance liquid chro-
Muscle Creatine Concentration. After local anesthesia and
incision of the skin, muscle samples were obtained from the
vastus lateralis muscle of the nondominant leg using a per-
cutaneous needle-biopsy technique modified to include suc-
Immediately after removal, the tissue samples were fro-
zen in liquid nitrogen and stored at 2808C for later analysis.
When all testing sessions were completed, the tissue samples
were packaged in dry ice and shipped overnight to a human
performance laboratory, where they were later freeze dried,
dissected free of any blood and connective tissue, and pow-
dered. The powdered muscle was then extracted with perchlo-
ric acid, neutralized, and analyzed enzymatically for muscle
Cr using a spectrophotometric analysis described by Harris et
Body Mass and Total Body Water Volume. Body mass
was assessed using a digital scale from the BOD POD Body
Composition Tracking System (Life Measurements, Inc, Con-
cord, CA). Total body water was determined using a deuterium
oxide dilution method, which has been shown to be a valid
and reliable measurement technique.
We administered
each subject an oral dose of deuterium oxide of approximately
0.15 g/kg of body mass, which was weighed out and diluted
with sterile water for intake. Before ingestion and after a 4-
hour equilibration period, two 5-mL venous blood samples
were drawn for comparison. After extraction from the blood,
the plasma was frozen at 2208C and stored for later analysis.
Samples were then packaged with dry ice and shipped over-
night to Metabolic Solutions, Inc (Nashua, NH), where deu-
terium enrichment in the body fluid was measured using iso-
tope ratio mass spectrometry.
The precision of this method
is 62%, and the percent coefficient of variation is typically
46 Volume 38
Number 1
March 2003
Urinary and Muscle Creatine, Body Mass, Total Body Water, and Intracellular Water After Loading and Maintenance with Either
Creatine or Placebo
Group and
(mean 6 SD)
Day 7
(mean 6 SD)
Day 28
(mean 6 SD)
Urinary creatine (mg/dL)
Muscle creatine (mg/kg dm‡)
Body mass (kg)
Total body water (L)
Intracellular water (L)
14.09 6 35.62
123.18 6 11.78
75.54 6 17.67*
41.98 6 11.78
24.44 6 7.40
454.09 6 290.74*†
146.99 6 25.63*†
76.29 6 18.04*
43.35 6 12.19*†
25.39 6 8.03
331.26 6 272.34*†
143.58 6 18.84*†
76.86 6 18.07*†
44.02 6 12.37*†
25.57 6 8.66
Urinary creatine (mg/dL)
Muscle creatine (mg/kg dm)
Body mass (kg)
Total body water (L)
Intracellular water (L)
8.12 6 7.52
127.99 6 13.20
72.94 6 15.72
41.34 6 8.93
24.00 6 5.59
14.22 6 48.83
124.28 6 13.65
73.61 6 15.92
42.21 6 9.08†
24.08 6 6.19
6.15 6 5.98
126.50 6 19.02
73.28 6 16.05
42.23 6 9.11†
23.70 6 7.16
*Significantly greater than placebo group (
, .05).
†Significantly greater than presupplementation (
, .05).
‡dm indicates dry mass.
0.75% daily.
Total body water was calculated as the deute-
rium-dilution space divided by 1.04, which corrects for ex-
change of the deuterium with nonaqueous hydrogen of body
We also assessed TBW using a Xitron 4200 multi-
frequency bioelectrical impedance analyzer (Xitron Technol-
ogies Inc, San Diego, CA). This was performed as a backup
measure in case we were unable to perform the dilution anal-
ysis on the plasma samples.
Intracellular Water and Extracellular Water Volumes.
The ECW compartment was determined using a sodium bro-
mide dilution method.
We administered each subject an
oral dose of sodium bromide (approximately 60 mg/kg of body
mass) simultaneously with the deuterium oxide solution. The
same blood samples taken for the deuterium analysis were also
used for the sodium bromide analysis, with the bromide con-
centration in the serum ultrafiltrate determined by high-per-
formance liquid chromatography (Metabolic Solutions, Inc).
Because of the extreme sensitivity of this method, small quan-
tities of bromide can be administered for the analysis, allowing
for sufficient washout between measurement days.
The cor-
rected bromide space was calculated and used to determine the
ECW volume.
The intracellular water (ICW) volume was
calculated by subtracting the ECW volume from the TBW
Statistical Analysis
We used the Statistical Package for the Social Sciences soft-
ware (version 10.0, SPSS Inc, Chicago, IL) to perform the
statistical analysis of the raw data. All dependent measures
were analyzed using a 1-within (time), 2-between (group and
sex) mixed design with repeated-measures analyses of vari-
ance and Tukey Honestly Significant Difference post hoc tests
to test differences between means. For all statistical tests, the
alpha level was set at .05.
Blood and Urine Analyses
Analyses for anabolic steroids and drugs of abuse were neg-
ative for all subjects at each testing date, and no differences
were observed in either group for blood or urine creatinine
concentrations. However, the time-by-group (F
5 25.56,
P 5 .000) and time-by-sex (F
5 4.04, P 5 .023) interac-
tions for urinary Cr concentration were significant. The Cr
group had significantly greater urinary Cr concentrations on
days 7 and 28 as compared with presupplementation, whereas
no changes were observed in the P group (Table). Further-
more, women experienced greater urinary Cr concentrations
than did men on days 7 and 28.
Muscle Creatine Concentration
Assays for Cr could not be completed for 4 subjects (2 each
in the Cr and P groups); thus, these subjects were not included
in the Cr analysis. The time-by-group interaction was signifi-
cant (F
5 4.75, P 5 .013): the Cr group had a greater Cr
concentration on days 7 and 28 as compared with presupple-
mentation (see Table). No changes were observed in the P
group. No differences were observed when the men and wom-
en within the Cr group were compared before or after supple-
Body Mass
A significant time-by-group interaction (F
5 3.30, P 5
.044) was observed for body mass, as the Cr group experi-
enced a significant increase from presupplementation to day
28 (see Table). The Cr group’s body mass on day 7 was 0.75
kg greater than at presupplementation; however, this change
was not significant. The Tukey post hoc test revealed that an
increase of 0.88 kg was necessary for statistical significance.
The P group did not experience any significant changes in
body mass. As expected, men had greater body mass than
women, but there were no significant sex interactions.
Total Body Water Volume
A significant time-by-group interaction (F
5 3.86, P 5
.027) was observed for TBW (see Table). Both groups expe-
rienced significantly greater TBW levels on days 7 and 28 as
compared with presupplementation, but the increase was great-
er in the Cr group. The Tukey post hoc test revealed that a
Journal of Athletic Training 47
difference of 0.86 L was necessary for statistical significance.
The differences of 0.87 and 0.89 L experienced by the P group
were just higher than this value. Although no difference ex-
isted between the groups before supplementation, the Cr group
had a significantly greater TBW volume on days 7 and 28
than did the P group. As expected, men had a greater TBW
than women; however, there were no significant sex interac-
Extracellular Water and Intracellular Water Volumes
As expected, men had greater ICW and ECW volumes, but
there were no sex interactions. No other significant main ef-
fects or interactions, including a time-by-group interaction
5 1.02, P 5 .366) for ICW, were observed. Further-
more, when ICW was expressed relative to the TBW, no sig-
nificant changes were noted.
We examined the changes in muscle Cr, body mass, and
body water during periods of Cr loading and maintenance in
men and women. The supplementation protocol was indeed
effective for increasing muscle Cr concentrations. The increas-
es in muscle Cr were associated with increases in both TBW
and body mass. However, only TBW increased during the
loading phase, whereas the increase in body mass was not
observed until both the loading and maintenance phases were
Muscle Creatine
Several reports indicate that muscle Cr concentration can be
elevated when a normal diet is supplemented with oral Cr.
Our Cr group experienced a 20% increase in Cr concentration
during the first week (loading phase) of supplementation. This
increase was then maintained throughout the remaining 3
weeks (maintenance phase).
As expected, a large amount of between-subject variability
was observed for the change in muscle Cr concentration from
presupplementation to the end of the loading phase. Similar
findings have been reported previously,
which may explain
why some individuals do not experience an ergogenic ef-
reported that 20% to 30% of individuals
do not respond to Cr supplementation (,10 mmol/kg dry mass
[dm] [8%] in muscle Cr concentration). Similarly, we ob-
served that 4 subjects (28%) in our study failed to respond to
the supplementation. The dosages we used were not adjusted
for body mass; thus, each subject ingested equal amounts of
Cr. Because of this, it might be expected that a greater effect
would be seen in individuals with smaller body mass. How-
ever, this was not observed because the nonresponders repre-
sented a wide range of body mass (57.09–86.21 kg). Further-
more, the increase experienced by women (body mass 5 63.63
6 12.58 kg) was not different from that experienced by men
(body mass 5 87.46 6 11.98 kg). This is not unexpected
because the 7-day loading protocol should have been sufficient
for maximizing muscle uptake regardless of body mass.
example, women ingesting Cr experienced a greater increase
in urinary Cr excretion than did men after both the loading
and maintenance phases. Although sex differences have not
been reported previously, they are not unexpected. Any Cr not
taken in by the muscle or other tissues remains in the plasma
and is eventually filtered through the kidneys and excreted in
the urine. Because of their lower body mass, women had less
available tissue for Cr uptake, resulting in a greater amount of
excess Cr. Thus, factors other than the relative dose-response
relationship play a role in the total Cr uptake by the muscle.
observed that 20% of individuals achieved Cr
concentrations of approximately 150 to 160 mmol/kg dm after
supplementation. This concentration is considered to be the
upper limit of muscle Cr stores, although some individuals,
including 4 subjects in the present study, achieve higher levels.
Whereas a number of factors have been suggested to affect
muscle Cr uptake, the primary determinant appears to be the
initial muscle Cr concentration.
The normal muscle Cr
concentration of the human vastus lateralis appears to be ap-
proximately 124 mmol/kg dm.
In our subjects, the average
muscle Cr concentration before supplementation was 125.6
mmol/kg dm, with a large amount of between-subject vari-
ability (105.9–150.8 mmol/kg dm). Our findings are consistent
with those of previous authors,
who reported a wide vari-
ation (100–150 mmol/kg dm) in the initial muscle Cr content.
Increases in muscle Cr concentration after supplementation ap-
pear to be inversely related to the initial Cr concentration.
In support of the above, we observed a significant correla-
tion between the initial Cr levels and the increases in muscle
Cr after supplementation (r 520.75, P , .01). Subjects in
the Cr group with an initial Cr concentration less than 120
mmol/kg dm experienced an average increase of 33.4
mmol/kg dm (23.1%), whereas subjects with an initial Cr con-
centration greater than 120 mmol/kg dm only experienced an
average increase of 16.6 mmol/kg dm (11.2%) during the load-
ing phase.
Body Mass
Previous investigators
have reported increases in
body mass after a loading phase of Cr supplementation. Al-
though the Cr group did experience an increase in the present
study, the increase did not reach significance until the entire
supplementation protocol had been completed (1.31-kg in-
crease after 28 days). In contrast, the P group failed to expe-
rience any significant changes in body mass. This is consistent
with other studies reporting increases after a protocol of Cr
loading and maintenance.
However, body mass mea-
surements were not taken immediately after the loading phase
in those studies. Thus, whether their subjects experienced any
immediate changes in body mass is unknown. In our study,
the increase observed in the Cr group after the loading phase
(0.75 kg) was slightly lower than what the Tukey post hoc test
demonstrated as necessary for significance (0.88 kg). This was
unexpected because increases of 0.70 and 0.75 kg after loading
had previously been found to be statistically significant.
However, our findings are not isolated because others
have also failed to observe significant body mass changes after
a loading phase of supplementation.
Although 4 subjects (including 3 women) in the Cr group
failed to experience an increase in body mass after 28 days of
supplementation, the range for those who did was consistent
with gains previously observed, from 0.47 to 3.92 kg.
At this time, the exact cause of the weight gain has not been
determined. However, increases in protein synthesis and water
retention are the 2 more commonly cited theories.
Protein Synthesis. It has been theorized that at least part
of the increase in body mass can be attributed to increased
48 Volume 38
Number 1
March 2003
protein synthesis and morphologic changes within the skeletal
Recently reported data suggest that Cr supplemen-
tation might amplify protein synthesis stimulation in response
to resistance training.
In that study, however, protein content
was only examined after 12 weeks of supplementation and
training. Thus, the effect of Cr after only 1 week or even after
4 weeks of training is unknown. As mentioned previously,
because a number of authors
reported increases in
body mass in as few as 5 to 7 days, it is unlikely that these
changes can be explained by protein synthesis alone.
Water Retention. The gains in body mass observed are
likely due to water retention during supplementation. Creatine
is an osmotically active substance. Thus, any increase in the
body’s Cr content should result in increased water retention
and consequent gains in body mass.
For example, 1 subject
in the present study, who reported having a fairly consistent
body mass throughout the previous year, experienced a 4.8-kg
increase in body mass during the first week of supplementa-
tion, 90% of which was accounted for by the increase in TBW.
The limited number of investigators
who have re-
ported TBW volumes during supplementation provide con-
trasting results. Significant increases in TBW have been ob-
served after 6
and 9
weeks of supplementation, whereas a
similar 4-week protocol failed to affect TBW.
whether the subjects in these studies actually experienced an
increase in muscle Cr is unknown because Cr concentrations
were not measured. Furthermore, in each of these studies, a
bioelectric impedance analysis was used to estimate TBW.
Such analysis is a prediction of TBW and is associated with
errors ranging from 1.5 to 2.5 L.
Dilution techniques, such
as the deuterium oxide and sodium bromide we used, are con-
sidered criterion measures of body water.
To our knowl-
edge, we are the first to directly measure muscle Cr and fluid
balance during supplementation, and our results suggest that
increases in muscle Cr concentrations are associated with wa-
ter retention. Both groups had similar TBW volumes at the
beginning of the study. However, although both groups ex-
perienced an increase in TBW during the first week of sup-
plementation, the Cr group’s TBW was significantly greater
than the P group’s TBW after both the loading and mainte-
nance phases (see Table). These findings support previous re-
search because the increase experienced by the Cr group
(4.86%) is similar to that observed using the bioelectric im-
pedance analysis measure (5.30% and 4.47%).
We initially theorized that water retention would be respon-
sible for the immediate gains in body mass after supplemen-
tation. As expected, the changes in TBW experienced by the
Cr group were similar to those observed for body mass. The
greatest increase in TBW (1.37 L) occurred during the first
week of supplementation, whereas the greatest difference com-
pared with presupplementation occurred after 28 days of sup-
plementation (2.04 L). It is interesting to note, however, that
the increase in TBW we observed would actually account for
a greater increase in body mass. We would expect that a TBW
increase of 1.37 L would be associated with a body mass in-
crease of approximately 1.37 kg. Yet, the Cr group only ex-
perienced a nonsignificant 0.75-kg increase during this time.
An explanation for this finding is not readily apparent but must
involve decreased caloric intake or increased caloric expen-
diture (or both) during supplementation. A BOD POD Body
Composition Tracking System digital scale was used for all
body mass measurements, and a dilution technique was used
to determine TBW. We also performed a bioelectric impedance
analysis assessment of TBW as a secondary measure. When
we analyzed these data, we observed a significant and identical
1.37-L increase in TBW after the loading phase. Thus, we do
not question the validity of our data.
Fluid Intake. During the loading phase, the subjects in both
groups ingested their respective supplements with approxi-
mately 454 mL of water 5 times per day. It is possible that
the increase in TBW content is the result of an increased fluid
intake during the week (;15.89 L). This is the most likely
explanation for the slight increase experienced by the P group.
However, the greater increase experienced by the Cr group
suggests that the subjects experienced greater water retention.
Thus, Cr uptake may have influenced water retention. Because
fluid intake and urinary volume were not assessed, we could
not determine whether increased fluid intake or decreased fluid
loss or both were responsible for the change in body water.
Caloric Intake and Expenditure. We instructed our sub-
jects to maintain their normal, habitual diet throughout the
supplementation period. Although we did not record dietary
intake, other authors
have reported consistent caloric in-
takes while increases in body mass occurred during supple-
mentation. Anecdotally, our subjects reported a decreased ap-
petite at times during the supplementation period because they
described a ‘full’ feeling from ingesting the supplement and
fluid on 5 occasions each day. Decreases in caloric intake dur-
ing supplementation have been previously reported.
tunately, TBW volumes were not assessed in those studies;
thus, it is unknown if they increased or not. It is also possible
that the subjects in the Cr group experienced an ergogenic
effect, allowing for greater training volume during this period.
This may have resulted in greater caloric expenditure. Thus,
it is possible that increased fluid intake, decreased caloric in-
take, and increased caloric expenditure are responsible for our
Intracellular Water Retention. Because Cr is primarily
stored intramuscularly (95%), it is more likely that the increase
in TBW would be intracellular because of the direct influx of
water into the muscle cell. Previous investigators
unable to determine whether increases in lean body mass were
due to cellular water retention or gains in actual muscle pro-
tein, because only TBW was assessed during supplementation.
More recently, however, fluid distribution has been assessed
but only using the bioelectric impedance analysis predic-
We directly measured fluid distribution using dilution
techniques and observed a 1.13-L (4.62%) increase in ICW in
the Cr group. However, this change was not statistically sig-
nificant. Increases in ICW have been reported previously using
the bioelectric impedance analysis prediction.
In those
studies, increases of 3.30 L (9.0%) and 1.00 L (4.93%) were
statistically significant.
The nonsignificant increase we observed accounted for
55.4% of the increase in TBW volume, which is fairly con-
sistent with normal fluid distribution (approximately two thirds
of the TBW is intracellular). This suggests an equal distribu-
tion of fluid during supplementation. Interestingly, an increase
in cell volume appears to be an anabolic proliferative signal,
which may be the first step in muscle protein synthesis.
Because of this, increased cell volume has been suggested as
a mechanism for protein synthesis stimulation and increased
muscle mass under conditions of muscular overload during Cr
Journal of Athletic Training 49
Adverse Effects
None of the blood or urinary measures suggested any ad-
verse effects as a result of supplementation. Furthermore, none
of the subjects in the present investigation experienced muscle
cramping or any other side effects (other than increased body
mass) during the supplementation protocol. However, whether
any subjects performed exercise bouts resulting in a large
amount of water loss is unknown. Thus, a potential relation-
ship between Cr supplementation and heat illness cannot be
established from the results of the present investigation.
Limitations of the Study
As mentioned previously, caloric and fluid intakes were not
recorded, and differences in either of these factors could have
influenced the changes in body mass and fluid balance. Fur-
thermore, each subject was involved in an individualized re-
sistance training program. These training protocols were not
controlled for; however, the volume of each training session
was recorded. Because of a large amount of variability across
subjects, a relationship between training volume and changes
in body mass and fluid balance could not be established. Fur-
thermore, training protocols before supplementation were not
recorded, so comparisons could not be made. Thus, it is pos-
sible that the differences in training volume may also have
influenced the changes in body mass and fluid balance.
Our results indicate that the supplementation protocol was
effective in increasing muscle Cr concentrations. Increased
muscle Cr content was associated with an increased body mass
and TBW volume. Thus, supplementation does result in water
retention. It was initially hypothesized that the water would be
preferentially retained intracellularly, altering fluid distribu-
tion. However, this was not observed. Therefore, the theory
of a Cr-related fluid shift is not supported because fluid dis-
tribution remained normal. An alteration in fluid distribution
during supplementation had been suggested as a cause of mus-
cle cramping and other heat-related problems anecdotally as-
sociated with Cr supplementation. Because the subjects failed
to experience any side effects beyond weight gain, it cannot
be determined whether athletes supplementing their habitual
diet with oral Cr monohydrate will be more predisposed to
muscle cramping and heat illness than athletes who are not
ingesting Cr. However, our results do not support the fluid-
shift theory behind Cr supplementation and heat illness. Thus,
from this investigation, a potential relationship between Cr
supplementation and heat illness cannot be established. It will
be of value for future researchers to focus on changes in fluid
balance and the occurrence of heat illness when Cr supple-
mentation is combined with fluid loss during exercise.
This work was supported in part by a grant from the National
Athletic Trainers’ Association Research and Education Foundation
and in part by a grant from the National Institutes of Health to the
University of Virginia, General Clinical Research Center, MO1
RR00847. We thank Dr Lori Wideman, Dr Judy Weltman, Sandra
Jackson, RN, and the University of Virginia General Clinical Re-
search Center staff for their assistance during the data collection. We
also thank Experimental and Applied Sciences (EAS) Inc, Golden,
CO, for supplying the Cr monohydrate used in the investigation.
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... Regarding the safety of creatine supplementation, several studies evaluating the hypothetical toxicity of creatine supplementation (at the recommended dose) in humans have not found any evidence of side effects for the kidney and liver [1,3,9,23]. In particular, a multicenter study of more than 1500 patients demonstrated no alterations in kidney and liver parameters associated with creatine supplementation [24]. ...
... The only directly demonstrated side effect of Cr supplementation is weight gain due to the increase in total intracellular body water without altering fluid distribution [23]. ...
... Creatine is an osmotically active substance known as a retention substance, driving water intracellularly, particularly in muscular cells where is present 95% of body creatine; although creatine supplementation increases total body water, fluid distribution is not altered [23]. Interestingly, an increase in cell volume appears to be an anabolic proliferative signal, which is supposed to be the first step in mouse protein muscular synthesis [104,105]. ...
Full-text available
Creatine supplementation has been one of the most studied and useful ergogenic nutritional support for athletes to improve performance, strength, and muscular mass. Over time creatine has shown beneficial effects in several human disease conditions. This review aims to summarise the current evidence for creatine supplementation in advanced chronic liver disease and its complications, primarily in sarcopenic cirrhotic patients, because this condition is known to be associated with poor prognosis and outcomes. Although creatine supplementation in chronic liver disease seems to be barely investigated and not studied in human patients, its potential efficacy on chronic liver disease is indirectly highlighted in animal models of non-alcoholic fatty liver disease, bringing beneficial effects in the fatty liver. Similarly, encephalopathy and fatigue seem to have beneficial effects. Creatine supplementation has demonstrated effects in sarcopenia in the elderly with and without resistance training suggesting a potential role in improving this condition in patients with advanced chronic liver disease. Creatine supplementation could address several critical points of chronic liver disease and its complications. Further studies are needed to support the clinical burden of this hypothesis.
... However, the impact of Cr on fluid distribution in the LP has yet to be explored in females. One previous study evaluated a mixed sample of males and females and reported a significant increase in TBW and body mass (BM), with no effect on ICF, after a 7-day loading, and 21-day maintenance supplementation protocol, only controlling for the MC phase at the pre-supplementation time point [18]. While prior mixed-sex studies demonstrated improved hydration-related outcomes with Cr loading in the follicular phase (FP) [19], the shift in fluid distribution that occurs in the LP highlights the need for a further understanding of how Cr supplementation may impact fluid distribution in females across the MC. ...
... Both NM subjects and those using HC, with controlled timepoints, were enrolled in order to improve the generalizability to females. Sample size estimation was determined a priori on the primary outcome variables of fluid distribution with an assumed average effect size of 0.45 and a power of 0.80 [15,18,[21][22][23], requiring a total sample size of 42 (n = 21 per treatment) based on previous studies. Post hoc power calculations demonstrated an average effect size of 1.28 and power of 0.90, demonstrating adequate power. ...
... In a sample of 13 well-trained males, significant increases in TBW (2.3 L) and BM (1.1 kg) were reported following Cr supplementation, with no significant changes for the PL in either TBW or BM (2.3 L and 0.1 kg, respectively) [15]. These findings are consistent with one mixed-sex study that demonstrated a significant increase in BM (0.75 kg; p < 0.05) and TBW (1.37 L; p < 0.05) following a 7-day Cr loading phase when compared to the PL group [18]. Powers et al. (2003) found no significant sex interactions despite noting smaller fluctuations in TBW and BM in the female subjects, however, sex-specific data were not analyzed. ...
Full-text available
This study examined the effects of creatine (Cr) loading on body mass (BM) and fluid markers of total body water (TBW), extra-cellular fluid (ECF), and intra-cellular fluid (ICF) across the menstrual cycle (MC). Thirty moderately active females, either naturally-menstruating (NM) or using hormonal contraceptives (HC), were randomized to Cr (Cr; 4 × 5 g/day of creatine monohydrate for 5 days; n = 15) or a non-caloric placebo (PL; n = 15) using a double-blind, placebo-controlled design, with a menstrual phase crossover. BM, TBW, ECF, and ICF were measured at pre- and post-supplementation in randomized order of follicular phase (FP; NM: MC days 0–8, HC: inactive pill days) or luteal phase (LP; NM: ≤15 days from next projected cycle start date, HC: active pill days) using bioelectrical impedance spectroscopy. Acute hydration status and salivary estrogen were used as covariates. Change in BM was not different between groups across MC ([PL-Cr] Δ 0.40 ± 0.50 kg; p = 0.427) or between MC phase across groups ([FP-LP] Δ 0.31 ± 0.48 kg; p = 0.528). TBW (p = 0.802), ECF (p = 0.373), and ICF (p = 0.795) were not different between supplement groups at pre-supplementation/FP time points. There were no significant differences between the NM and HC subjects at any time point, for any outcome (p > 0.05). Following LP supplementation, significant changes were observed in TBW (Cr: Δ 0.83 ± 0.38 L, PL: Δ −0.62 ± 0.38 L; p = 0.021), ECF (Cr: Δ 0.46 ± 0.15 L, PL: Δ −0.19 ± 0.15 L; p = 0.013), and ICF (Cr: Δ 0.74 ± 0.23 L, PL: Δ −0.02 ± 0.23 L; p = 0.041). These data demonstrate an increase in all fluid compartments in the LP following Cr loading, without observed alterations in body weight for females.
... Regardless of this calculation error, this is still 83% higher than the 12% increase in muscle creatine content reported by Hultman et al. (1996) after ingesting 3 g of CM for 14 days. Most creatine loading studies using 20 g of CM per day only report average increases of muscle creatine content of ∼15%-25% in participants after 5-7 days of loading when carbohydrates are excluded (Harris et al., 1992;Hultman et al., 1996;Powers et al., 2003;Syrotuik & Bell, 2004). As stated previously, using lower quantities of creatine supplementation (i.e., 3 g of CM) raises muscle content creatine levels to only ∼12% . ...
... It should also be noted that the authors of this study reported muscle creatine content levels in millimole per kilogram of wet weight, but it is customary to report muscle creatine content level in millimole per kilogram of dry weight as reported in various creatine publications (Febbraio et al., 1995;Hultman et al., 1996;Kreider et al., 2017;Powers et al., 2003). Nevertheless, the content of water in muscle has been reported to range from ∼75% to 79% (Hargens et al., 1983;Mannion et al., 1993;Mitchell et al., 1945;Ward & Lieber, 2005) with a mean content of ∼77%; thus, data between muscle wet weight and muscle dry weight can be compared by applying the following conversion factor: 1 mmol/kg dry muscle mass = 0.23 mmol/kg wet muscle mass (Mannion et al., 1993). ...
... Despite the myriad of potential mechanisms purported to augment muscular hypertrophy, intracellular water retention appears to be central. In an RCT consisting of men (n = 16) and women (n = 16), loading with creatine (25 g/d for 7 d) resulted in an increment of »1.4 L (41.98 § 11.78 to 43.35 § 12.19 L) in total body water, whereas 3 subsequent weeks using a maintenance dose of 5 g/d increased total body water by 2.1 L (41.98 § 11.78 to 44.02 § 12.37 L) compared with baseline [71]. This increase in total body water was predominantly intracellular [71]. ...
... In an RCT consisting of men (n = 16) and women (n = 16), loading with creatine (25 g/d for 7 d) resulted in an increment of »1.4 L (41.98 § 11.78 to 43.35 § 12.19 L) in total body water, whereas 3 subsequent weeks using a maintenance dose of 5 g/d increased total body water by 2.1 L (41.98 § 11.78 to 44.02 § 12.37 L) compared with baseline [71]. This increase in total body water was predominantly intracellular [71]. Total body water increased by 2.3 L (47.8 § 3.6 to 50.2 § 4.7 L) following creatine loading (0.3 g¢kg¢d À1 for 7 d) in soccer players [72], which despite a small sample size (n = 7 for the creatine group), the total body water was measured using the deuterium oxide dilution technique, which is considered the gold standard [73]. ...
Creatine supplementation has been shown to increase measures of lean body mass (LBM), however there is often high heterogeneity across individual studies. Therefore, we systematically reviewed and meta-analyzed randomized controlled trials (RCTs) investigating creatine supplementation on LBM. Sub-analyses were performed based on age, sex, and type of exercise. Based on PRISMA guidelines, we searched the following databases: Pubmed, SPORTDiscus, Web of Science, and Scopus (PROSPERO register: CRD42020207122) until May 2022. RCTs that investigated creatine supplementation on LBM were included. Animal studies and studies on individuals with specific diseases were excluded. Thirty-five studies were included, totaling 1192 participants. Overall (i.e., inclusion of all studies with and without exercise training interventions) revealed that creatine increased LBM by 0.68 kg (CI95%: 0.26, 1.11). Sub-analyses revealed greater gains in LBM when creatine was combined with resistance training [mean difference (MD): 1.10 kg; CI95%: 0.56, 1.65], regardless of age. There was no statistically significant effect of creatine on LBM when combined with mixed exercise (MD: 0.74 kg; CI95%: -3.89, 5.36) or without exercise (MD: 0.03 kg; CI95%: -0.65, 0.70). Further sub-analyses found that males on creatine increased LBM by 1.46 kg (CI95%: 0.47, 2.46), compared to a non-significant increase of 0.29 kg (CI95%: -0.43, 1.01) for females. In conclusion, the addition of creatine supplementation to a resistance training program increases LBM. During a resistance training program, males on creatine respond more favorably compared to females.
... Estos cambios pueden producirse en valores como masa corporal magra (LBM), masa corporal (BM), masa grasa (FM) y masa libre de grasa (FFM). Este suplemento puede aumentar la masa muscular incrementando la síntesis de proteínas [96] e incrementando la presión osmótica en el músculo [101][102][103]. ...
... Además, el HMB podría aumentar la oxidación de las grasas, mejorando la biogénesis mitocondrial mediante la activación de PGC-1α y, por lo tanto, reduciendo el porcentaje de masa grasa [131]. Por otro lado, se ha propuesto la suplementación con CrM para aumentar la masa muscular al aumentar la presión osmótica en el músculo, con lo que aumentaría el contenido de agua muscular [101][102][103], y a su vez promoverá la síntesis de glucógeno [14,15]. ...
Full-text available
El monohidrato de creatina (CrM) y el β-hidroxi β-metilbutirato (HMB) son suplementos deportivos ampliamente estudiados. Sin embargo, no está claro cómo actúan cuando se utilizan conjuntamente en el ámbito deportivo. Hay que añadir que la incógnita es todavía mayor, cuando hablamos de un deporte de carácter predominantemente aeróbico como el remo. Los objetivos de esta tesis han sido: 1) determinar mediante una revisión sistemática la eficacia de mezclar CrM más HMB en comparación con sus efectos aislados sobre el rendimiento deportivo, la composición corporal, los marcadores de daño muscular inducidos por el ejercicio (EIMD) y las hormonas anabólico-catabólicas. 2) determinar la eficacia y el grado de potenciación de 10 semanas de suplementación con CrM más HMB en el rendimiento deportivo, que se midió mediante una prueba incremental en remeros tradicionales de élite masculinos. 3) determinar el efecto y el grado de potenciación de 10 semanas de suplementación con CrM más HMB en los EIMD y hormonas anabólicas/catabólicas. En base a los objetivos planteados, los principales resultados de la tesis indican que: 1) La combinación de CrM más 3 g/día de HMB durante 1–6 semanas podría producir efectos positivos en el rendimiento deportivo (fuerza y rendimiento anaeróbico) y durante 4 semanas en la composición corporal (aumento de grasa masa libre y disminución de la masa grasa). 2) La ingesta de CrM más HMB durante 10 semanas mostró un efecto sinérgico sobre la potencia aeróbica durante una prueba incremental. 3) La combinación de CrM más HMB presentó un efecto sinérgico sobre la testosterona y la ratio testosterona/cortisol y un efecto antagonista sobre el cortisol en comparación con la suma de la suplementación individual o aislada. Las conclusiones obtenidas en la presente tesis doctoral indican que la combinación de estos dos suplementos puede ser de gran ayuda para los profesionales que rodean al deportista para mejorar el rendimiento aeróbico y la recuperación.
... This enhancement was commensurate with an overall greater creatine-specific increase in half-squat and leg press repetition number, ostensibly via realizing a greater volume-load earlier amidst the 12-week training timeframe. While it is reasonable to assume that the significantly-albeit minimally-increased repetitions achieved by CRE may explain the aforementioned greater relative body mass largely through skeletal muscle mass accretion, these results should be interpreted cautiously; it remains possible that the aforementioned body mass augmentations were due to increases in creatine-mediated total body water content [11,24]. Therefore, the use of more sensitive techniques such as bioelectrical impedance analysis, commensurate with detailed skeletal muscle mass assessment via dual X-ray absorptiometry or-more ideallyultrasonography may provide further insight into the mechanisms underlying the observed weight changes [25][26][27]. ...
Full-text available
Creatine monohydrate supplementation in females is largely under-represented in the literature, and their potentially differential hemodynamic responses are unknown. Methods: Twentyeight resistance-trained women (25.5 ± 6.1 years, 59.7 ± 6.3 kg, 163 ± 5 cm) were randomly assigned to the supplement creatine monohydrate (CRE; 5 g creatine monohydrate + 5 g dextrose) or placebo (PLA; 10 g dextrose) four times per day for 7 days in a double-blind fashion. Each subject subsequently completed resistance training sessions (3 × week) for four weeks with four sets to muscular failure of both half-squat and leg press exercises. The change in body mass (BM), exercise repetition number (REP), rated perceived exertion (RPE), and cardiovascular variables were assessed (sessions 1, 6, and 12). Statistical analyses were performed at a significance level of p ≤ 0.05. Results: Analyses revealed a significant CRE-specific BM increase (p = 0.013), as well as significantly greater halfsquat (p = 0.006) and leg press (p = 0.017) REP per set versus PLA. Additionally, CRE demonstrated significantly lower relative RPE values at session 12 compared with previous sessions. Any significant main or interaction effects were observed for the studied cardiovascular variable. Conclusions: The present data substantiate the creatine’s efficacy to improve muscular performance in females while demonstrating the safety of combined creatine monohydrate supplementation and resistance training on cardiovascular parameters.
... One study reports a significant increase in fat-free mass following 3 days of loading and 7 days of maintenance supplementation at a dose of 20 and 5 g/day, respectively (Safdar et al., 2008). However, this gain in fat-free mass is most likely due to increased fluid retention following Cr supplementation (Bone et al., 2017;Powers et al., 2003) rather than a true increase in myofibrillar protein content. As such, the lack of a significant gain in LBM for our study is in line with what is expected in response to 2 weeks of Cr supplementation. ...
Full-text available
Creatine (Cr) supplementation is a well-established strategy to enhance gains in strength, lean body mass, and power from a period of resistance training. However, the effectiveness of creatyl-L-leucine (CLL), a purported Cr amide, is unknown. Therefore, the purpose of this study was to assess the effects of CLL on muscle Cr content. Twenty-nine healthy men ( n = 17) and women ( n = 12) consumed 5 g/day of either Cr monohydrate ( n = 8; 28.5 ± 7.3 years, 172.1 ± 11.0 cm, 76.6 ± 10.7 kg), CLL ( n = 11; 29.2 ± 9.3 years, 170.3 ± 10.5 cm, 71.9 ± 14.5 kg), or placebo ( n = 10; 30.3 ± 6.9 years, 167.8 ± 9.9 cm, 69.9 ± 11.1 kg) for 14 days in a randomized, double-blind design. Participants completed three bouts of supervised resistance exercise per week. Muscle biopsies were collected before and after the intervention for quantification of muscle Cr. Cr monohydrate supplementation which significantly increased muscle Cr content with 14 days of supplementation. No changes in muscle Cr were observed for the placebo or CLL groups. Cr monohydrate supplementation is an effective strategy to augment muscle Cr content while CLL is not.
... We emphasize this observation, especially for polydipsia, since creatine is an osmotically active substance [95]. We hypothesized that the higher intramuscular water retention and slower release to the extracellular medium would lead to dehydration [96] and interfere with this outcome. Nevertheless, as observed elsewhere [30,97,98], the water balance was not affected. ...
Full-text available
Diabetes mellitus (DM) is a worldwide health concern, and projections state that cases will reach 578 million by 2030. Adjuvant therapies that can help the standard treatment and mitigate DM effects are necessary, especially those using nutritional supplements to improve glycemic control. Previous studies suggest creatine supplementation as a possible adjuvant therapy for DM, but they lack the evaluation of potential morphological parameters alterations and tissue injury caused by this compound. The present study aimed to elucidate clinical, histomorphometric, and histopathological consequences and the cellular oxidative alterations of creatine supplementation in streptozotocin (STZ)-induced type 1 DM rats. We could estimate whether the findings are due to DM or the supplementation from a factorial experimental design. Although creatine supplementation attenuated some biochemical parameters, the morphological analyses of pancreatic and renal tissues made clear that the supplementation did not improve the STZ-induced DM1 injuries. Moreover, creatine-supplemented non-diabetic animals were diagnosed with pancreatitis and showed renal tubular necrosis. Therefore, even in the absence of clinical symptoms and unaltered biochemical parameters, creatine supplementation as adjuvant therapy for DM should be carefully evaluated.
... Other muscle solutes, including elements that can be acutely changed, contribute to its osmotic environment. It is well documented that rapid creatine supplementation protocols are associated with an increase (~1 kg) in body mass that is largely attributed to a gain in body water [44][45][46]. Results from the larger study from which the Bone MuscleSound ® data were collected included a 6% increase in muscle creatine concentrations and a 22% increase in muscle glycogen when their respective loading protocols were undertaken according to best practice principles [29]. The corresponding changes in total body water and intracel-lular water, measured via BIS, were 1.3% and 1.4% (creatine loaded), and 2.3% and 2.2% (glycogen loaded), respectively [29]. ...
Full-text available
Researchers and practitioners in sports nutrition would greatly benefit from a rapid, portable, and non-invasive technique to measure muscle glycogen, both in the laboratory and field. This explains the interest in MuscleSound®, the first commercial system to use high-frequency ultrasound technology and image analysis from patented cloud-based software to estimate muscle glycogen content from the echogenicity of the ultrasound image. This technique is based largely on muscle water content, which is presumed to act as a proxy for glycogen. Despite the promise of early validation studies, newer studies from independent groups reported discrepant results, with MuscleSound® scores failing to correlate with the glycogen content of biopsy-derived mixed muscle samples or to show the expected changes in muscle glycogen associated with various diet and exercise strategies. The explanation of issues related to the site of assessment do not account for these discrepancies, and there are substantial problems with the premise that the ratio of glycogen to water in the muscle is constant. Although further studies investigating this technique are warranted, current evidence that MuscleSound® technology can provide valid and actionable information around muscle glycogen stores is at best equivocal.
... The safety of creatine supplementation has been thoroughly investigated, and when used appropriately, short-and long-term supplementation (up to 30 g·d −1 for 5 years) is safe and well-tolerated in healthy individuals. The only reproducible side effects that have been consistently observed are weight gain (a potential 1 kg to 2 kg increase after creatine loading), primarily as a result of water retention, and decreased urine output (11,12). Other side effects that have been anecdotally reported include nausea, diarrhea, and related gastrointestinal distress, muscle cramps, and heat intolerance. ...
Creatine is a popular and widely used ergogenic dietary supplement among athletes, for which studies have consistently shown increased lean muscle mass and exercise capacity when used with short-duration, high-intensity exercise. In addition to strength gains, research has shown that creatine supplementation may provide additional benefits including enhanced postexercise recovery, injury prevention, rehabilitation, as well as a number of potential neurologic benefits that may be relevant to sports. Studies show that short- and long-term supplementation is safe and well tolerated in healthy individuals and in a number of patient populations.
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Two intermittent high-intensity exercise protocols were performed before and after the administration of either creatine or a placebo, and performance characteristics and selected physiological responses were studied. Each exercise protocol consisted of 10 6-s bouts of high-intensity cycling at 2 exercise intensities (130 rev/min [EX130]: ∼820 W and 140 rev/min [EX140)]: ∼ 880 W) so that in EX130 the same amount of exercise was performed before and after the administration period, whereas an exercise intensity in EX140 was chosen to induce fatigue over the 10 exercise bouts. Sixteen healthy male subjects were randomly assigned to the 2 experimental groups. A double-blind design was used in this study. There were no significant changes in the placebo group for any of the measured parameters. Performance towards the end of each exercise bout in EX140 was enhanced following creatine supplementation, as shown by a smaller decline in work output from baseline along the 10 trials. Although more work was performed in EX140, after vs before the administration period, blood lactate accumulation decreased (mean and SEM), from 10.8 (0.5) to 9.1 (0.8) mmol·l−1 and plasma accumulation of hypoxanthine decreased from 21.1 (0.4) to 16.7 (0.8) μmol·l−1, but there was no change in oxygen uptake measured during 3 exercise and recovery periods [3.18 (0–1) vs 3.14 (0.1) l·min−1]. In EX130 blood lactate accumulation decreased, from 7.0 (0.5) to 5.1 (0.5) mmol·l−1, and oxygen uptake was also lower, decreasing from 2.84 (0.1) to 2.78 (0.1) l·min−1. A significant increase in body mass (11 kg: range 0.3 to 2.5 kg) was found in the creatine group. The mechanism responsible for the improved performance with creatine supplementation are postulated to be both a higher initial creatine phosphate content availability and an increased rate of creatine phosphate resynthesis during recovery periods. The lower blood lactate and hypoxanthine accumulation can also be explained by these mechanisms.
This study examined the effects of 26 days of oral creatine monohydrate (Cr) supplementation on near-maximal muscular strength, high-intensity bench press performance, and body composition. Eighteen male powerlifters with at least 2 years resistance training experience took part in this 28-day experiment. Pre and postmeasurements (Days 1 and 28) were taken of near-maximal muscular strength, body mass, and % body fat. There were two periods of supplementation: Days 2 to 6 and Days 7 to 27. ANOVA and t-tests revealed that Cr supplementation significantly increased body mass and lean body mass with no changes in % body fat. Significant increases in 3-RM strength occurred in both groups, both absolute and relative to body mass; the increases were greater in the Cr group. The change in total repetitions also increased significantly with Cr supplementation both in absolute terms and relative to body mass, while no significant change was seen in the placebo (P) group. Creatine supplementation caused significant changes in the number of BP reps in Sets 1, 4, and 5. No changes occurred in the P group. It appears that 26 days of Cr supplementation significantly improves muscular strength and repeated near-maximal BP performance, and induces changes in body composition.
The effects of creatine supplementation on force-time curve (FTC) characteristics were investigated in collegiate track athletes. Sixteen male and 20 female athletes were randomly divided into a placebo (P, n = 21) and a creatine (Cr, n = 15) group. Six weeks of supplementation consisted 0.3 g per kilogram of body weight per day of Cr monohydrate or non-nutritive placebo. Subjects were involved in a periodized weight-training program centered on explosive exercises. Pretesting and posttesting consisted of 7-site skinfold analysis, countermovement vertical jump (CMJ), and static vertical jump (SJ). SJ was performed on a 61.0-[chi] 121.9-cm ATMI (Advanced Medical Technologies, Newton, MA) force plate and was analyzed for FTC. No differences were found between the 2 treatments for FTC. The CMJ showed a significant group by time interaction with the Cr group improving at a greater rate than did the P group. Lean body mass (LBM) significantly increased in the Cr group after the treatment period. These results suggest that 6 weeks of Cr supplementation can favorably enhance LBM and CMJ performance in track athletes. (C) 2000 National Strength and Conditioning Association
Anaerobic working capacity (AWC) estimated from the critical power test provides a theoretically and experimentally valid estimate of work capacity associated with muscle energy reserves adenosine triphosphate and phosphocreatine. Creatine monohydrate (CM) supplementation has been shown to increase phosphocreatine stores in skeletal muscle and, in theory should increase AWC. Therefore, the purpose of this study was to examine the effects of supplementation with CM, CM plus carbohydrate (CHO), or CHO alone on AWC. Using a double-blind random design, 26 young men (mean age +/- SD, 19.9 +/-1.6 years) were assigned to 1 of 3 treatment conditions: (a) 35 g of flavored CHO powder as a placebo (PL, n = 8); (b) 5.25 g of CM and 1 g of CHO in a flavored powder blend (CM, n = 9); and (c) 5.25 g of CM and 33 g of CHO in flavored powder blend (CM-CHO, n = 9). The subjects completed 3 phases of testing on an electronically braked cycle ergometer: (a) familiarization (3 learning trials to establish power outputs for subsequent testing); (b) pretesting (4 bouts performed at power outputs selected to elicit fatigue in 1-10 minutes); and (c) posttesting (4 bouts performed at the same power outputs as pretesting but completed after ingesting the supplements 4 times per day for 6 consecutive days). The results indicated that CM and CM-CHO supplementation significantly (p <= 0.05) increased AWC by 9.4 and 30.7%, respectively These data suggest that 33 g of CHO may augment the effects of CM supplementation on AWC. (C) 1999 National Strength and Conditioning Association
Thirty-six (16 men, 20 women) collegiate track and field athletes (sprinter, jumpers, and throwers) were randomly divided into a placebo (P, n = 21) group and a creatine supplemented (C, n = 15) group. Six weeks of supplementation consisted of 0.30 g?kg-1?d-1 of creatine monohydrate (Crm) or a placebo. Subjects were involved in a preseason conditioning program that consisted of interval sprinting and multijoint, large-muscle-group weight-training movements programmed in a periodized manner. Pretesting (PRE) and posttesting (POS) consisted of a 7-site skinfold analysis, hydrostatic weighing, countermovement vertical jump, static vertical jump, and 5 +/- 10-second maximum cycle ergometer rides. Data were analyzed using G T analysis of variance. Significant interactions occurred for several variables. Creatine effected superior gains (percent change creatine vs. placebo) in countermovement vertical jump height (7.0 vs. 2.3%), countermovement vertical jump power index (6.8 vs. 3.1%), average cycle peak power (12.8 vs. 4.8%), cycle average power (10.8 vs. 3.1%), cycle total work (10.8 vs. 3.5%), cycle initial rate of power production (30.0 vs. 11.2%), and lean body mass. These results suggest that 6 weeks of Crm intake can favorably enhance vertical jump, power output, work capacity, and lean body mass in men and women collegiate track and field athletes following a periodized training program. (C) 1999 National Strength and Conditioning Association
The purpose of this study was to test the validity of a multiple frequency bioimpedance spectroscopy (BIS) technique that estimates extracellular fluid volume (ECV), intracellular fluid volume (ICV), and total body water (TBW). Thirteen healthy males (mean +/- SD: age, 23 +/- 3 yr; body mass, 80.6 +/- 14.7 kg) had their TBW and ECV measured by ingesting dilution tracers (7.27 g deuterium oxide, 1.70 g sodium bromide; blood samples at 0 and 4 h). ICV was calculated as TBW minus ECV. Impedance was measured (50-500 kHz) at rest, on a nonconducting surface, with a BIS analyzer. Electrode placement, posture, exercise, food/fluid intake, and ambient temperature were controlled. Dilution measures (TBW, 51.00 +/- 9.30; ECV, 19.88 +/- 3.14; ICV, 31.12 +/- 6.80 L) and BIS volumes (TBW, 50.03 +/- 7.67; ECV, 20.95 +/- 3.33; ICV, 29.04 +/- 4.51 L) were significantly different for ECV (P < 0.01) and ICV (P < 0.05); some individual differences were large. The correlation coefficients of dilution versus BIS volumes (r = 0.93 to 0.96) were significant at P < 0.0001; SEEs were: TBW, 2.23 L; ECV, 1.26 L; and ICV, 1.71 L. We concluded that BIS is valid for between-subject comparisons of body fluid compartments, is appropriate in clinical settings where change in ECV/ICV ratio is important, and should be used by comparing the required level of accuracy to the inherent technique error/variance.
1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated. 2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak. 3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%. 4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content. 5. No side effects of creatine supplementation were noted. 6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
A high-pressure liquid chromatographic method for bromide measurement is used to determine extracellular water volume in humans. The method uses 5 microL serum ultrafiltrate and has a sensitivity of 7.5 pmol. Because of the extreme sensitivity of this method, relatively small quantities of Br can be administered and small amounts of blood are needed for the analysis. By this method, the mean corrected Br space in 82 healthy adults representing a wide range of body weights was 0.218 +/- .034 L/kg (mean +/- 1 SD) with a range of 0.153-0.295 L/kg, which is consistent with reported values. There was a significant, inverse relationship between corrected Br space per kilogram and obesity as measured by body mass index. The corrected Br space in six children aged 3-36 mo was 0.335-0.394 L/kg, which is also consistent with reported values in children of this age. This method for Br measurement can easily and readily be applied for the determination of extracellular water volume.