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ORIGINAL ARTICLE
Jeff S. Volek Æ Nicholas A. Ratamess Æ Martyn R. Rubin
Ana L. Go
´
mez Æ Duncan N. French
Michael M. McGuigan Æ Timothy P. Scheett
Matthew J. Sharman Æ Kei jo Ha
¨
kkinen
William J. Kraemer
The effects of creatine supplementation on muscular performance
and body composition responses to short-term resistance
training overreaching
Accepted: 6 November 2003 / Published online: 18 December 2003
Springer-Verlag 2003
Abstract To determine the effects of creatine supple-
mentation during short-term resistance training over-
reaching on performance, body composition, and resting
hormone concentrations, 17 men were randomly as-
signed to supplement with 0.3 g/kg per day of creatine
monohydrate (CrM: n=9) or placebo (P: n=8) while
performing resistance exercise (5 days/week for 4 weeks)
followed by a 2-week taper phase. Maximal squat and
bench press and explosive power in the bench press were
reduced during the initial weeks of training in P but not
CrM. Explosive power in the bench press, body mass,
and lean body mass (LBM) in the legs were augmented
to a greater extent in CrM (P £ 0.05) by the end of the
6-week period. A tendency for greater 1-RM squat
improvement (P=0.09) was also observed in CrM.
Total testosterone (TT) and the free androgen index
(TT/SHBG) decreased in CrM and P, reaching a nadir
at week 3, whereas sex hormone binding globulin
(SHBG) responded in an opposite direction. Cortisol
significantly increased after week 1 in CrM (+29%),
and returned to baseline at week 2. Insulin was signifi-
cantly depressed at week 1 ()24%) and drifted back
toward baseline during weeks 2–4. Growth hormone
and IGF-I levels were not affected. Therefore, some
measures of muscular performance and body composi-
tion are enhanced to a greater exten t following the
rebound phase of short-term resistance training over-
reaching with creatine supplementation and these
changes are not related to changes in circulating hor-
mone concentrations obtained in the resting, postab-
sorptive state. In addition, creatine supplement ation
appears to be effective for maintaining muscul ar per-
formance during the initial phase of high-volume resis-
tance training overreaching that otherwise results in
small performance decrements.
Keywords Cortisol Æ Muscle strength Æ Overtraining Æ
Power Æ Testosterone Æ Weight training
Introduction
We have previously demonstrated that creatine supple-
mentation enhances performance of maximal strength,
explosive power, and muscular endurance after 7 days
(Volek et al. 1997b, 1999). In a follow-up study, we re-
ported that creatine supplementation in conjunction
with a resistance training program augmented gains in
muscular strength, lean body mass, and muscular
hypertrophy (Volek et al. 1999). Several others studies
lasting 3 weeks (Burke et al. 2000) to 13 weeks (Larson-
Meyer et al. 2000) have reported similar ergogenic effects
of creatine on adaptations to resistance training. The
mechanism(s) by which creatine exerts this ergogenic
effect on chronic adaptations to training is/are contro-
versial and may be due to greater gains in lean body
mass (Volek et al. 1999), an effect on protein metabolism
(Parise et al. 2001), an increase in myosin heavy chain
mRNA and protein expressio n (Willoughby and Rosene
2001), an alteration in the expression of myogenic
transcription factors (Hespel et al. 2001), an increase in
satellite cell mitotic activity (Dangott et al. 1999), an
increase protein synthesis secondary to an increase in
cell swelling (Bemben et al. 2001; Haussinger et al. 1993),
J. S. Volek (&) Æ N. A. Ratamess Æ M. R. Rubin
A. L. Go
´
mez Æ D. N. French Æ M. M. McGuigan
T. P. Scheett Æ M. J. Sharman Æ W. J. Kraemer
Human Performance Laboratory, Department of Kinesiology,
University of Connecticut, Storrs, CT 06269, USA
E-mail: jeff.volek@uconn.edu
Tel.: +1-860-4866712
Fax: +1-860-4861123
K. Ha
¨
kkinen
Neuromuscular Research Centre and
Department of Biology of Physical Activity,
University of Jyvaskyla, Jyvaskyla, Finland
Eur J Appl Physiol (2004) 91: 628–637
DOI 10.1007/s00421-003-1031-z
or simply an increase in the intensity of individual
workouts resulting from a better match between ATP
supply and demand during exercise (Casey et al. 1996).
Resistance training results in increases in muscle fiber
hypertrophy and muscle size, a result of an increase in net
protein balance. The magnitude of muscle hypertrophy is
heavily influenced by nutrition and the anabolic and cat-
abolic hormonal milieu (Kraemer et al. 1995). Such hor-
monal signals create greater stimuli for increased receptor
interactions and gene level transcription and translation
of proteins (Turner et al. 1988). In turn, protein synthesis
is increased, which sets the stage for greater protein
accretion and muscle fiber hypertrophy with chronic
resistance training. Only a few studies have examined
whether the ergogenic effect of creatine on adaptations to
training is mediated by a change in circulating hormones.
Our labo ratory report ed that acute creatine supplemen-
tation for 7 days did not alter responses of testosterone,
cortisol, and hormones involved in regulation of water
balance (renin, aldosterone, angiotensin, arginine vaso-
pressin) to a single bout of heavy resistance exercise
(Volek et al. 1997b, 2001). Creatine supplementation
(20 g/day for 5 days) failed to alter testosterone, cortisol,
and growth hormone (GH) responses to a single bout of
heavy resistance exercise (Op T Eijnde and Hespel 2001).
Although acute creatine supplementation does not appear
to alter the responses of testosterone, cortisol, and GH to
a single bout of resistance exercise, hormone levels could
be altered over a prolonged resistance training program,
especially an overreaching-type program, which often
results in perturbations of the endocrine system (Fry et al.
1993).
We have previously shown that amino acid supple-
mentation is effective for maintaining musc ular strength
and power during high-volume resistance training
overreaching (Ratamess et al. 2003). In that investiga-
tion, we developed a model of overreaching that resulted
in performance decrements initially, followed by a sub-
stantial ‘‘rebound effect’’ leading to improvements in
muscular strength and power. However, the effect of
creatine supplementation on resistance training over-
reaching is not well understood. Therefore, the primary
purpose of the present study was to investigate whether
creatine supplementation affected the hormonal re-
sponses to short-term resistance training overreaching
and the relationship to changes in muscular performance
and body composition.
Methods
Experimental design
A double-blind, randomized study was employed using two experi-
mental groups (creatine or placebo supplementation) who under-
went 4 weeks of resistance training (5 days/week) and
supplementation. The training program consisted of 2 weeks of
moderate-intensity/high-volume and 2 weeks of high-intensity/
moderate-volume resistance training. Acute overreaching was
produced by training the whole body on consecutive days, thereby
minimizing recovery in between workouts (Ratamess et al. 2003). At
the end of each training week, resting blood samples were obtained
and muscular performance was assessed. This experimental design
enabled us to investigate the time course of potential ergogenic effects
of creatine supplementation (e.g., recovery enhancement) during
resistance training overreaching in resistance-trained men.
Subjects
Seventeen resistance-trained men were randomly assigned to a
creatine monohydrate (CrM) or a placebo (P) group. The subjects
had the following characteristics [mean(SE)]: CrM group (n=9):
age=20.7 (1.9) years; height=179.3 (4.7) cm; body mass=88.5
(17.0) kg; and training experience=5.4 (2.1) years; P group (n=8):
age=21.3 (3.0) years; height=179.4 (6.4) cm; body mass=88.9
(11.1) kg; and training experience=5.1 (3.0) years. There were no
significant differences between groups in physical characteristics.
Each of the subjects was informed of the benefits and risks of
the investigation and subsequently signed an approved consent
form in accordance with the guidelines of the University Institu-
tional Review Board for use of human subjects. No subject had
any medical or orthopedic problem that would compromise his
participation and performance in the study. None of the subjects
were taking any medications, nutrition supplements (including
creatine for at least 8 weeks), or anabolic drugs that would con-
found the results of this study.
Resistance training
Prior to initiation of the 4-week overreaching program, each par-
ticipant underwent 4 weeks of base resistance training. This en-
sured that each subject began the study in a trained state. Base
training consisted of five exercises per workout (squat, bench press,
lat pull down, leg press, and seated shoulder press) for three sets of
8–10 repetitions with 1–3 min of rest in between sets performed for
2 days/week. Multiple-set, periodized resistance training was per-
formed on 4 consecutive days using a total-body program
(Table 1). Due to time limitation constraints with the subjects, the
overreaching program utilized training each muscle group on
consecutive days, thereby limiting recovery. The first 2 weeks
consisted of a higher volume, moderate intensity of resistance
exercise whereas the last 2 weeks consisted of high intensity with a
moderate volume of resistance exercise. All sets were performed
with repetition maximum (RM) loads such that all sets were either
performed to or near muscular exhaustion. When each subject was
able to complete the desired number of repetitions with the current
load, weight was added to subsequent sets or during the next
workout. All workouts were supervised by a certified strength and
conditioning specialist who also monitored the training loads
(Mazzetti et al. 2000). Following the 4-week experimental period,
each participant underwent a 2-week reduced-volume/frequency
resistance training phase. The program used during this phase was
identical to the base resistance training program used prior to
initiation of the 4-week overreaching protocol. Only week squat,
bench press, peak power attained during the ballistic bench press,
and jump squat were assessed following this training 2-week phase.
Supplementation and nutritional protocol
Subjects assigned to the CrM group ingested creatine monohydrate
in capsule form (Creatine Fuel, Twin Laboratories, Hauppauge,
N.Y., USA) at a dose 0.3 g/kg per day (divided into three equal
doses) for the 1st week and 0.05 g/kg per day (one dose) for the
remaining 3 weeks of training. This supplementation protocol in-
creased muscle creatine levels in our prior work (Volek et al. 1999).
Subjects in the P group consumed the same number of capsules
identical in appearance (powdered cellulose). All supplement doses
were administered by a registered dietician who calculated each
serving size and distributed the supplements in clearly marked
629
plastic bags. All subjects recorded the times of supplementation in
accordance with the investigators instructions. In order to control
for possible confounding effects of alterations in dietary intake over
the training period and to isolate the independent effects of the
supplementation treatments, an attempt was made to standardize
dietary nutrient intake at an isocaloric level for each subject. Prior
to beginning the study, subjects were weighed before and after a
seven-day period during which time they recorded all fooday/bev-
erages consumed according to instructions provided by the same
registered dietitian. If body weight fluctuated >1 kg during the 7-
day period, then subjects were provided with nutritional counseling
to either increase or decrease food intake in order to maintain body
weight. The seven-day food records were subsequently photocopied
and returned to subjects. Subjects reproduced this 7-day diet during
each week of the training and supplementation period.
Performance testing
Muscle testing (strength, power, local muscular endurance) was
performed prior to initiation of the 4-week overreaching period,
and after the completion of each training week. In addition, 1-RM
testing was performed after a 2-week reduced volume and fre-
quency period. 1-RM strength was determined for the free-weight
squat and bench-press exercises according to methods previously
described by Kraemer and Fry (1995). A warm-up set of five to ten
repetitions was performed using 40–60% of the perceived maxi-
mum 1-RM. After a 1-min rest period, a set of two to three repe-
titions was performed at 60–80% of the perceived maximum 1-RM.
Subsequently, three to four maximal trials (one-repetition sets)
were performed to determine the 1-RM. Rest periods in between
trials were 2–3 min. A complete range of motion and proper
technique were required for each successful 1-RM trial. For the
squat exercise, each subject was instructed to descend until the
upper thighs were parallel to the ground. A research assistant was
located lateral to the subject and gave a verbal ‘‘up’’ signal to
initiate the concentric action of the exercise. For the bench press,
each subject lowered the bar until it came in contact with the chest
musculature. ‘‘Bouncing’’ the weight off of the chest and excessive
arching of the back were not permitted. Strength testing was per-
formed at the same time each session and approximately 24 h
following the last training session. All subjects refrained from
activity not related to the present investigation for at least 24 h
prior to testing.
Power testing was performed prior to initiation of the training
program and after each 2-week phase. Upper and lower body
power was measured using the ballistic bench press and jump
squat exercises, respectively, with the Ballistic Measurement Sys-
tem (BMS; Norsearch Limited, Lismore, Australia). The BMS
enables ballistic movement and has been described in detail else-
where (Volek et al. 1997b). For the jump squat, each subject
descended to a position in which the thigh musculature was
parallel to the ground. In a ballistic manner, each subject as-
cended as rapidly as possible and proceeded to jump as high as
possible while minimizing any contributions from the arms. The
weight was released upon jumping and bar displacement was
calculated via a rotary encoder attached to the BMS and inter-
faced with a computer. For the ballistic bench press, each subject
lowered the weight from the fully extended elbow position until it
came in contact with the chest musculature. The concentric action
of the exercise was performed as rapidly as possible and the
weight was released upon completion. The BMS incorporates a
unidirectional electromagnetic braking system, which immediately
prevented descending bar movement once engaged; thus, the bar
was safely released. The jump squat and ballistic bench press were
performed with a load corresponding to 30% of the squat and
bench press 1-RM, respectively, attained during the pre-training
testing period. Testing order was randomized such that half of the
subjects began with the squat jump and half began with the
ballistic bench press. Each subject was given three to five maximal
trials with 2 min of rest in between trials and the largest power
output attained was recorded for analysis.
Following peak power testing, each subject performed a 20-
repetition jump squat protocol used to measure high-intensity local
muscle endurance. Loading for this assessment consisted of 30% of
each subjects pre-training 1-RM squat. Subjects were instructed to
jump as high as possible for each repetition while maintaining
proper exercise technique and range of motion. Mean power was
assessed at five repetition intervals and the percentage decline was
calculated: [(mean power reps. 1–5))(mean power reps 16–20)/
mean power rep 1–5]·100.
Body composition
Body mass was measured on a digital platform scale to the
nearest 100 g. Total body water (TBW) was estimated via bio-
electrical impedance analysis using a modified scale platform
Table 1 Resistance–training program
Monday, Wednesday Tuesday, Thursday Friday
Week 1
Back squat 3·10–12
a
Leg press 3·10–12
a
1-RM squat
Bench press 3·10–12
a
Incline bench press
3·10–12
a
1-RM bench
press
Lat pulldown 3·10–12
c
Bent-over row
3·10–12
c
Lunge 3·10–12
c
Stiff-leg deadlift
3·10–12
c
Seated shoulder press
3·10–12
c
Upright row 3·10–12
c
Dumbbell curl
3·10–12
c
Barbell curl 3·10–12
c
Lying triceps
extension 3·10–12
c
Dips 3·10–12
c
Leg raise 3·20
a
Sit-ups 3·20
a
Week 2
Back squat 3·8–10
a
Leg press 3·8–10
a
Squat
Bench press 3·8–10
a
Incline bench press
3·8–10
a
Bench press
Lat pulldown 3·8–10
c
Bent-over row 3·8–10
c
Jump squats
Lunge 3·8–10
c
Stiff-leg deadlift
3·8–10
c
Ballistic bench
press
Seated shoulder press
3·8–10
c
Upright row 3·8–10
c
Dumbbell curl
3·8–10
c
Barbell curl 3·8–10
c
Lying triceps extension
3·8–10
c
Dips 3·8–10
c
Leg raise 3·20
a
Sit-ups 3·20
a
Week 3
Back squat 5·5
a
Leg press 5·5
a
Squat
Bench press 5·5
a
Incline bench press
5·5
a
Bench press
Deadlift 5·5
c
High pull 5·5
c
Lat pulldown 5·5
c
Bent-over row 5·5
c
Seated shoulder
press 5·5
c
Close-grip bench
press 5·5
c
Week 4
Back squat 5·3
a
Leg press 5·3
a
Squat
Bench press 5·3
a
Incline bench press
5·3
a
Bench press
Deadlift 5·3
c
High pull 5·3
c
Jump squats
Lat pulldown 5·3
c
Bent-over row 5·3
c
Ballistic bench
press
Seated shoulder press
5·3
c
Close-grip bench
press 5·3
c
a
3 min of rest between sets
b
2 min of rest between sets
c
1 min of rest between sets
630
mounted with pressure electrodes in contact with the feet (TBF-
105 Body Fat Analyzer; Tanita Corporation of America, Skokie,
Ill., USA). Repeat TBW measurements obtained on 12 men on
four occasions separated by 1 week between tests demonstrated a
coefficient of variation of 1.8%. Percentage body fat and bone
mineral density were obtained using dual-energy X-ray absorp-
tiometry (DEXA) with a total body scanner (Prodigy; Lunar
Corporation, Madison, Wis., USA) that uses a constant potential
X-ray source of 76 kVp and a cerium filter that produces dual-
energy peaks of 38 and 62 keV. All analyses were performed by
the same technician using computer algorithms (software version
2.17.008). Quality assurance was assessed by analyzing a phan-
tom spine provided by the company and daily calibrations were
performed prior to all scans using a calibration block provided
by the manufacturer. Intra-class correlation coefficients (R‡0.98)
were obtained for bone mineral content, lean body mass, and fat
mass from repeated scans on a group of ten men and women in
our laboratory who were tested on 2 consecutive days.
Side effects
Resting pulse was measured by palpation of the radial artery and
blood pressure was measured with a sphygmomanometer by the
same investigator. In order to assess potential side effects and
subjective changes in body function to the supplementation regi-
men a questionnaire used in prior creatine studies by our labora-
tory (Volek et al. 2000, 2001) was provided to subjects at the end of
the study. The questionnaire asked subjects which group they
thought were in and assessed changes in appetite, thirst, skin,
muscle cramping, stomach distress, diarrhea, flatulence, headache,
sex drive, sleepiness, nervousness, and aggression.
Biochemical analyses
Blood samples were obtained before and after each training week
via venipuncture, after 5 min in a supine position, in the early
morning hours (between 0500 and 0930 hours), and after a 10-h
overnight fast and abstinence from exercise for at least 12 h.
Blood sampling occurred during a standardized time of day for
each subject in order to minimize the effects of diurnal hormonal
variations. Whole blood samples were processed and centrifuged
at 1,500 g. Serum and/or plasma was harvested and stored at
)80C until analyzed. Whole blood was used to determine
hemoglobin in duplicate using the cyanmethemoglobin method at
540 nm (Sigma Diagnostics, St. Louis, Mo., USA) and hemat-
ocrit was analyzed in triplicate via standard microcapillary
techniques and microcentrifugation. Serum glucose concentra-
tions were measured in duplicate using standard colorimetric
procedures at 450 nm (Sigma Diagnostics). Serum creatine kinase
(CK) and plasma ammonia concentrations were determined in
duplicate using standard colorimetric procedures at 340 nm
(Sigma Diagnostics). Serum uric acid concentrations were
determined in duplicate using standard colorimetric procedures
at 520 nm (Sigma Diagnostics). Serum total testosterone, human
GH, sex-hormone binding globulin (SHBG), insulin-like growth
factor-1 (IGF-1), insulin, and cortisol concentrations were
determined in duplicate using standard radioimmunoassay (RIA)
techniques. Serum total testosterone, cortisol, insulin, and SHBG
were measured with
125
I solid-phase RIA (Diagnostic Products,
Los Angeles, Calif., USA). Serum IGF-1 was measured with
125
I
solid-phase RIA using an extraction procedure (Diagnostic
Products). Serum 22 kDa GH was measured using a
125
I liquid-
phase RIA with double-antibody technique (Nichols Institute
Diagnostics, San Juan Capistrano, Calif., USA). All samples for
each hormone were determined in duplicate in the same assay to
avoid interassay variance and were thawed only once for each
assay procedure. Intra-assay variance was less than 5% for all
hormones.
Statistical analyses
Statistical evaluation of the data was accomplished by using a two-
way analysis of variance (ANOVA) with one between- (CrM and P)
and one within- (time) factor after normal data distribution was
determined. When a significant F value was achieved, a Fishers
LSD test was used to locate the pairwise differences between means.
An independent t-test was used to analyze the delta change in
performance improvements between 0 and 6 weeks of the study.
Relationships among baseline hormones and the changes in hor-
mone concentrations to changes in performance and body com-
position measures were examined using Pearsons product-moment
correlation coefficients. Using the nQuery Advisor software (Sta-
tistical Solutions, Saugus, Mass., USA) the statistical power for the
n size used ranged from 0.80 to 0.92. Significance was set at
P £ 0.05.
Results
Performance
There were significant main time effects for 1-RM squat
and bench press and a significant interaction effect for
the squat when considering the change from week 0 to
week 1 (Fig. 1). Maximal squat was unchanged at
week 1 in CrM and progressively increased each week
thereafter. However, 1-RM squat was significantly re-
duced after week 1 in P but returned to baseline values
by week 2. 1-RM bench press significantly decreased in
P but remained unchanged in CrM at week 1, was not
different from baseline at week 2, and progressively in-
creased each week thereafter. Analysis of the delta
change in 1-RM squat performance from weeks 0–6
revealed only a trend for greater improvement in CrM
than P (P=0.09) but not with the 1-RM bench press.
There were significant main time effects for explosive
peak power in the jump squat and a significant time and
interaction effect for the ballistic bench press (Fig. 2).
Jump-squat peak power was unchanged at weeks 2 and
4 and significantly increased after the reduced frequency/
volume phase. There was a trend for the CrM group to
experience a greater increase at week 6 (group·time,
P=0.154). Ballistic bench press peak power significantly
decreased at week 2 in P but did not change in CrM
(group·time, P=0.053) and was significantly higher at
weeks 4 and 6 in CrM than P. The decline in mean
power during the 20 repetition jump squat protocol
ranged between –12% and –14% for both groups. Power
output was unchanged at weeks 2 and 4 but increased
significantly after the reduced volume/frequency phase
at week 6 (Table 2).
Body composition
There were significant main time effects for changes in
total body mass, lean body mass, fat mass and per-
centage body fat (Table 3). The increases in body
mass and lean body mass tended to be greater in the
CrM group. A similar pattern of response was ob-
served for the legs with the CrM group demonstrating
631
a significantly greater increase in lean body mass in
this region. Compared to baseline, total body water
(kg) was significantly increased at weeks 1, 2, 3, and 4
in the creatine group. There were no significa nt
changes in TBW expressed as a percent of body mass
nor were there any changes in bone mineral content or
bone mineral density for either group (data not
shown).
Hormonal responses
Hormonal responses are presented in Table 4. There
were significant main time effects for total testoster-
one, free androgen index (FAI: total testosterone/
SHBG), cortisol, and insulin, and a trend for SHBG
(P<0.06). Total testosterone decreased in CrM and P,
reaching a nadir at week 3 ()11% and –19%,
Fig. 2 Peak power during the jump squat (upper graph) and
ballistic bench press (lower graph) during 4 weeks of resistance
training overreaching and after a 2-week reduced volume/frequency
phase. There were significant main time effects and a group·time
interaction effect for the ballistic bench press. *P £ 0.05 from
baseline for collapsed means (upper graph) and from corresponding
creatine or placebo baseline (lower graph). Values are mean (SE)
Fig. 1 Maximal squat (upper graph) and bench press (lower graph)
strength during 4 weeks of resistance training overreaching and
after a 2-week reduced volume/frequency phase. Data analyzed
with a 2·6 (weeks 0–6) and 2·2 (week 0–1) ANOVA. *P £ 0.05
from baseline for collapsed means;
#
significant (P £ 0.05) group·-
time (week 0–1) interaction effect. Values are mean (SE)
Table 2 Mean power output
(W) during the 20-repetition
jump-squat protocol. Values
are mean (SD). %
Decline=[(mean power
repetitions 1–5))(mean power
repetitions 16–20)/mean
power repetitions 1–5]·100
Repetitions % Decline Main time
effect
Group·
time
1–5 6–10 11–15 16–20
Week 0 CrM 1,522 (293) 1,457 (282) 1,387 (282) 1,319 (240) )13.4% 0.068 0.674
P 1,470 (193) 1,410 (189) 1,361 (172) 1,278 (154) )13.1%
Week 2 CrM 1,502 (292) 1,455 (288) 1,404 (285) 1,310 (247) )12.8% 0.024 0.619
P 1,461 (136) 1,408 (131) 1,347 (115) 1,272 (133) )12.9%
Week 4 CrM 1,498 (320) 1,462 (296) 1,391 (260) 1,287 (248) )14.1% 0.016 0.503
P 1,441 (128) 1,399 (115) 1,321 (86) 1,242 (979 )13.8%
Week 6 CrM 1,586 (298) 1,551 (298) 1,491 (290) 1,396 (289) )12.0% 0.057 0.792
P 1,485 (89) 1,445 (88) 1,386 (83) 1,304 (102) )12.2%
632
respectively) and returning to baseline at week 4.
Serum SHBG responded in an opposite direction to
that of total testosterone. The FAI was significantly
decreased at week 1 and reached the lowest point at
week 3. Free testosterone responded in a similar
fashion but the changes were not significant. The CrM
group exhibited a significant increase in cortisol after
week 1 (+29%), which returned to baseline by
week 2; whereas cortisol was unchanged in the P
group. Insulin levels were significantly depressed at
week 1 and drifted back toward baseline during
weeks 2–4. GH and IGF-I levels were not significantly
altered over the training study. There were no signif-
icant relationships betwe en baseline hormone levels or
the changes in hormones with changes in performance
or body composition.
Table 3 Total and regional
body composition responses
determined using dual-energy
X-ray absorptiometry (DXA).
Values are mean (SD). BM
Body mass,LBM soft tissue lean
body mass, FM fat mass, BMC
bone mineral content
Total Creatine group Placebo group P
Week 0 Week 4 D Week 0 Week 4 D Main time
effect
Group·
time
BM
scale
(kg) 86.7 (16.9) 89.2 (16.7) +2.5 88.9 (11.1) 89.8 (10.5) +0.9 0.000 0.002
BM
DXA
(kg) 87.3 (16.5) 89.9 (16.6) +2.6 89.3 (11.1) 90.5 (10.2) +1.2 0.000 0.115
% Fat 17.4 (9.2) 16.1 (9.5) )1.3 20.2 (8.8) 19.3 (8.6) )0.9 0.001 0.467
LBM (kg) 67.2 (5.6) 70.6 (5.8) +3.4 66.9 (5.4) 68.9 (6.0) +2.0 0.000 0.153
FM (kg) 16.5 (12.1) 15.8 (12.5) )0.7 18.8 (10.4) 18.1 (9.9) )0.7 0.022 0.994
BMC (g) 3,577 (401) 3,555 (395) )22 3,652 (302) 3,566 (247) )86 0.105 0.321
Arms
% Fat 15.1 (10.3) 16.0 (11.4) +0.9 17.5 (9.0) 16.6 (8.6) )0.9 0.994 0.557
LBM (kg) 8.7 (0.6) 8.3 (2.9) )0.4 8.3 (0.7) 8.8 (1.1) +0.5 0.858 0.374
FM (kg) 1.8 (1.4) 1.7 (1.6) )0.1 2.0 (1.2) 1.9 (1.0) )0.1 0.080 0.611
BMC (g) 528 (70) 519 (67) )9 588 (123) 534 (61) )54 0.108 0.245
Legs
%Fat 18.0 (8.0) 16.4 (8.0) )1.6 20.2 (7.2) 18.7 (7.7) )1.5 0.002 0.417
LBM (kg) 22.0 (2.5) 23.6 (2.7) +1.6 21.7 (2.0) 22.3 (1.9) +0.6 0.000 0.022
FM (kg) 5.5 (3.4) 5.3 (3.6) )0.2 6.0 (2.7) 5.8 (2.6) )0.2 0.046 0.927
BMC (g) 1,425 (134) 1,426 (139) +1 1,291 (461) 1,391 (106) +100 0.422 0.430
Trunk
% Fat 18.3 (10.6) 17.3 (10.8) )1.0 21.9 (10.3) 20.9 (10.1) )1.0 0.112 0.940
LBM (kg) 32.5 (2.9) 33.7 (2.7) +1.2 32.8 (3.5) 33.8 (3.0) +1.0 0.007 0.699
FM (kg) 8.6 (7.1) 8.3 (7.1) )0.3 10.2 (6.3) 9.9 (6.2) )0.3 0.116 0.973
BMC (g) 1,132 (190) 1,012 (385) )120 1,151 (131) 1,151 (100) 0 0.342 0.336
Table 4 Blood hormonal responses in subjects who supplemented with creatine monohydrate (CrM) or placebo ( P). Values are
mean (SD).FAI Free androgen index, GH growth hormone, IGF-I insulin-like growth factor-I, SHBG sex hormone binding globulin, TT
total testosterone
Week 0 Week 1 Week 2 Week 3 Week 4 Main time
effect
Group · time
TT (nmol/l) CrM 34.8 (9.8) 34.2 (7.6) 34.0 (6.9) 31.0 (10.9)* 33.3 (8.0) 0.019 0.715
P 29.9 (6.2) 27.0 (5.6) 26.2 (2.8) 24.3 (3.1) 28.7 (6.8)
SHBG (nmol/l) CrM 21.4 (10.2) 22.6 (12.2) 22.7 (10.8) 22.2 (6.2)* 23.7 (9.7)* 0.053 0.150
P 22.9 (8.9) 24.9 (10.1) 25.2 (10.4) 27.6 (12.0) 24.9 (10.9)
FAI (TT/SHBG) CrM 1.77 (0.53) 1.66 (0.37)* 1.64 (0.46)* 1.41 (0.39)* 1.49 (0.36)* 0.000 0.437
P 1.51 (0.69) 1.25 (0.52) 1.19 (0.45) 1.02 (0.38) 1.29 (0.47)
Free T (pmol/l) CrM 126 (37) 124 (29) 129 (33) 120 (33) 125 (24) 0.554 0.500
P 105 (25) 94 (28) 89 (18) 93 (32) 97 (27)
Cortisol (nmol/l) CrM 614 (164) 792 (314)
**, ***
582 (186) 607 (154) 465 (219)
**
0.009 0.008
P 590 (157) 465 (138) 483 (159) 454 (145) 467 (62)
Insulin (IU/ml) CrM 11.0 (9.5) 8.2 (6.5)* 8.5 (5.8)* 8.7 (6.1)* 9.2 (5.9) 0.042 0.972
P 10.7 (8.2) 8.2 (5.7) 9.4 (7.9) 8.6 (6.9) 9.5 (9.0)
GH (ng/ml) CrM 0.23 (0.08) 0.21 (0.06) 0.24 (0.11) 0.30 (0.27) 0.23 (0.08) 0.249 0.586
P 0.22 (0.07) 0.31 (0.14) 0.29 (0.11) 0.32 (0.14) 0.32 (0.14)
IGF-I (nmol/l) CrM 39.9 (5.9) 38.9 (3.6) 38.1 (2.4) 0.414 0.167
P 43.8 (9.9) 47.0 (13.0) 45.0 (10.8)
*Significantly different (P £ 0.05) from week 0 value for collapsed group means
**Significantly different (P £ 0.05) from week 0 value for CrM group
***Significantly different (P £ 0.05) from corresponding value for P group
633
Blood metabolite responses
Metabolic responses are presented in Table 5. There was
a significant time and interaction effect for uric acid.
Uric acid increased in the P group at week 1 (+18%)
and gradually returned to baseline by week 3, whereas
values declined in the CrM group at week 1 ()11%) and
remained below baseline through week 4. Ammonia
values were reduced at week 1 and tended to remain
below baseline through week 4. CK was significa ntly
elevated at week 1 and returned toward baseline over
the remainder of the study. Glucose was significantly
lower at week 1 and remained below baseline through
week 4. There were no significant changes in total ch o-
lesterol and triglycerides. Hemoglob in and hem atocrit
values were reduced at week 1 and remained below
baseline through week 4. Plasma creatinine was signifi-
cantly increased in the CrM group (+5–8%) and un-
changed in the P group.
Side effects
There were no significant changes in resting heart rate or
blood pressure responses. Reported side effects were
minimal and occurred at a similar frequency for both
groups. The most common complaint was increased
thirst (two placebo and three creatine subjects) and
sleepiness (three creatine subjects). In the CrM group,
seven subjects reported not knowing their supplement
group and two thought they were in the P group. In the
P group, two subjects reported not knowing their sup-
plement group, five thought they were in the CrM
group, and one thought he was in the P group.
Discussion
A major aim of this study was to assess whether the
resting circulating hormonal milieu was altered by cre-
atine supplementation and whether this was related to
changes in performance and body composition during
resistance training overreaching. The findin gs from this
study indicate that alterations in resting hormones do
not explain the performance and body composition re-
sponses to creatine supplementation and short-term
resistance training overreaching in a group of men with
similar training backgrounds. Although the overreach-
ing protocol resulted in significant changes in the cir-
culating endocrine milieu, creatine supplementation
does not appear to be mediating its effect though hor-
monal mechanisms. These results were obtained in a
homogenous group of resistance-trained men. We
intentionally chose men with a resistance training
background in order to reduce the large variations that
can occur in strength gains at the onset of a structured
program in untrained individuals (e.g. , neural adapta-
tions which could potentially mask any supplement ation
benefits). To further equate the training status of all
subjects, we trained each subject for 4 weeks using a
structured base program before matching and random-
izing subjects into supplementation groups. This type of
standardization is also necessary in order to minimize
the effect of differences in hormone concentrations that
may exist between subjects as a result of training.
Previous work indicates that 5–7 days of creatine
supplementation does not alter hormonal responses to a
single bout of heavy resistance exercise (Op T Eijnde
and Hespel 2001; Volek et al. 1997a, 2001). However,
Table 5 Blood metabolite responses in subjects supplemented with creatine monohydrate (CrM) or placebo (P). Values are mean (SD).
CK Creatine kinase, TC total cholesterol, TG triglycerides, Hb hemoglobin, Hct hematocrit
Week 0 Week 1 Week 2 Week 3 Week 4 Main time
effect
Group·time
Uric acid (mg/dl) CrM 6.1 (1.3) 5.4 (1.5)
**
5.3 (1.6)
**
5.1 (1.4)
**
5.0 (1.4)
**
0.000 0.002
P 6.1 (1.6) 7.2 (2.4)
**
6.6 (1.7) 6.1 (1.7) 5.6 (1.8)
Ammonia
(lmol/l)
CrM 42.8 (19.1) 24.1 (21.3)
*
23.8 (18.0)
*
34.5 (17.4) 27.0 (19.0) 0.000 0.424
P 38.2 (18.4) 20.5 (13.3) 17.1 (5.0) 35.5 (18.7) 37.2 (13.2)
CK (IU/l) CrM 91 (69) 836 (920)
*
242 (124) 228 (146) 142 (74) 0.000 0.617
P 72 (38) 1297 (1630) 177 (79) 162 (106) 88 (47)
Glucose (mg/dl) CrM 95.4 (10.5) 87.1 (7.2)
*
92.8 (7.2)
*
88.5 (6.3)
*
90.4 (7.0)
*
0.000 0.472
P 97.9 (8.9) 90.0 (10.0) 92.8 (9.3) 89.0 (8.6) 88.2 (4.5)
TC (mg/dl) CrM 190 (38) 181 (38) 187 (45) 189 (41) 193 (30) 0.406 0.430
P 189 (46) 181 (38) 191 (36) 180 (35) 180 (51)
TG (mg/dl) CrM 81 (31) 69 (32) 82 (40) 89 (42) 92 (44) 0.292 0.127
P 126 (91) 99 (74) 126 (94) 102 (59) 90 (63)
Hb (g/dl) CrM 15.2 (1.0) 15.1 (1.2)
*
14.9 (1.0)
*
14.7 (0.9)
*
14.9 (0.8)
*
0.005 0.192
P 15.7 (1.1) 14.6 (1.0) 15.0 (0.6) 14.8 (1.0) 14.8 (0.6)
Hct (%) CrM 44.9 (2.4) 42.2 (1.9)
*
42.3 (1.9)
*
43.1 (1.9)
*
43.2 (1.5)
*
0.000 0.957
P 44.4 (2.0) 41.3 (2.4) 42.0 (1.6) 42.4 (2.0) 42.8 (1.3)
Creatinine (mg/dl) CrM 1.65 (0.09) 1.74 (0.09)
**
1.76 (0.13)
**, ***
1.77 (0.09)
**, ***
1.79 (0.13)
**, ***
0.005 0.000
P 1.60 (0.07) 1.60 (0.07) 1.54 (0.04) 1.57 (0.03) 1.61 (0.06)
*Significantly different (P £ 0.05) from week 0 value for collapsed
group means
**Significantly different (P £ 0.05) from week 0 value for corre-
sponding CrM or P group
***Significantly different (P £ 0.05) from corresponding value for
P group
634
exercise-induced (acute) and resting (chronic) hormone
concentrations may be controlled by different regulatory
mechanisms and reflect the systems ability to cope with
an applied exercise stress versus a regulatory mechanism
to which the involved tissues are constantly exposed
(Fry et al. 199 1). Since changes in resting hormones
would be more likely to contribute to the changes in
performance and bod y composition resulting from a
training progra m, this study focused on the effects of
creatine supplementation on resting hormones. The
overreaching protocol resulted in significant decreases in
total testosterone, FAI, and insulin whereas SHBG and
cortisol were significantly increased.
The reduction in total testosterone was expected since
it has been shown that resting total testosterone de-
creases during high volume or high intensity resistance
training overreaching (Fry et al. 1993; Raastad et al.
2001). Although not significant, SHBG concentrations
tended to increase more in the P group, which may have
been due to the need to increase the carrying capacity of
testosterone stimulated by a reduced availability of free
testosterone. It has been previously shown that free
testosterone also decreases when the volume an day/or
intensity are significantly increased (Ha
¨
kkinen et al.
1987; Ha
¨
kkinen and Pakarinen 1991).
The significant increase in cortisol concentrations at
week 1 in the CrM but not the P group was unexpected
since we failed to observe changes in resting or exercise-
induced levels of cortisol after 7 days of creatine sup-
plementation in our prior work (Volek et al. 1997b,
2001). However, Op Teijnde and Hespel (2001) recently
reported that cortisol levels were significantly higher 90
and 120 min after an acute bout of heavy resistance
exercise following 5 days of creatine supplementation.
Resting concentrations of cortisol have been shown to
be highly variable over the course of various resistance
training programs (Fry and Kraemer 1997). Generally,
significant increases in volume or intensity result in
higher resting concentrations of cortisol (Ha
¨
kkinen et al.
1987; Ha
¨
kkinen and Pakarinen 1991). The increased
cortisol response at week 1 could have been due to a
direct effect of creatine or more likely due to the greater
force-producing capabil ities (and exertion during train-
ing) exhibited by the CrM group.
Resting concentrations of serum 22-kD GH were not
significantly altered by the resistance training program,
which is consistent with our prior work in younger and
older populations (Krae mer et al. 1999). A recent study
demonstrated that creatine supplementation augmented
the GH response to a bout of heavy resistance exercise
(Schedel et al. 2000); however, creatine had no effect on
GH responses to resistance exercise in another study (Op
T Eijnde and Hespel 2001). GH has been shown to
stimulate the release of IGF-I from the liver with peak
values of IGF-I occurring approximately 16–28 h fol-
lowing GH stimulation (Copeland et al. 1980). Circu-
lating IGF-I levels also tend to be more sensitive to
changes in nutritional intake than exercise stress,
and can be elevated by protein and carbohydrate
supplementation in young men engaged in daily bouts
of heavy resistance exercise (Kraemer et al. 1999). The
results of the present study indicate that short-term
resistance training overreaching, with or without crea-
tine supplementation, does not alter resting concentra-
tions of GH or IGF-1.
Resting serum glucose and serum insulin concentra-
tions were reduced throughout the experimental period
in both groups at several time points. These findings are
unique as to our knowledge reductions in resting serum
glucose have not typically been observed during resis-
tance training. However, basal concentrations of insulin
are not regulated by normal basal serum glucose con-
centrations (e.g., 80–100 mg/dl) and have been shown to
be lower during strength training (Miller et al. 1984) and
in bodybuilders wi th large muscle mass (Szczypaczewska
et al. 1989). Although insulin secretion is pulsatile and a
basal value may not be indicative of a positive training
adaptation, our data support previous investigations
and may show greater insulin sensitivity during resis-
tance training overreaching.
In several of our performance measures, creatine
supplementation generally resulted in improved perfor-
mance responses to the overreaching protocol [i.e.,
maintenance of muscular performance during the high-
volume phase, a statistically greater improv ement in the
ballistic bench press peak power output, and a tendency
(P=0.09) for a greater improvement in wee k squat].
Several other studies have reported that creatine sup-
plementation augments gains in musc ular after resis-
tance training programs lasting 3 weeks (Burke et al.
2000), 4 weeks (Arciero et al. 2001; Earnest et al. 1995;
Kelly and Jenkins 1998; Kreider et al. 1998), 5 weeks
(Stone et al. 1999), 6 weeks (Burke et al. 2001), 8 weeks
(Noonan et al. 1998), 9 weeks (Bemben et al. 2001),
10 weeks (Vandenberghe et al. 1997), 12 weeks (Volek
et al. 1999), and 13 weeks (Larson-Meyer et al. 2000).
Unique to this study, the same muscle groups were
trained 5 days in a row, thus reducing the amount of
recovery time between workouts to less than 24 h. The
mechanism for the performance improvements in the
creatine group could be due to a number of factors, but
a hormonal-mediated effect is not likely.
Creatine supplementation during resistance training
has been shown to accentuate muscle fiber hypertrophy
(Hespel et al. 2001; Volek et al. 1999), muscle cross-
sectional area (Hespel et al. 2001), myosin heavy chain
mRNA and protein expression (Willoughby et al. 2001),
and whole body leucine oxidation and plasma leucine
rate of appearance (Parise et al. 2001). In the present
study, the CrM group gained more lean body mass and
this was statistically significant in the legs. The magni-
tude of change in total body lean body mass (+3.4 kg)
was slightly greater than previously reported gains
ranging from 1.6 to 2.5 kg after 4 weeks of resistance
training and creatine in previous studies (Arciero et al.
2001; Earnest et al. 1995; Kelly and Jenkins 1998;
Kreider et al. 1998). This may be attributed to the
overreaching program used in the present study. The
635
short-term program used in the present study was peri-
odized (i.e., variation in the volume and intensity) and
supervised by a certified strength and conditioning
specialist, thus ensuring optimal effort during training
(Mazzetti et al. 2000). In addition, the subjects had
5 years of resistance training experience. It has been
shown that hypertrophy may be the major mechanism
for strength improvement in trained individuals
whereas neural mechanisms predominate in novice lift-
ers (Ha
¨
kkinen 1989). Thus, training status may have
been an influential factor affecting the magnitude of
lean body mass gain in the present study and in other
studies using previously untrained individuals.
Serum concentrations of uric acid were significantly
elevated in the P group, whereas values were reduced
in the CrM group. Elevated concentrations of uric
acid may reflect an intracellular energy deficit (via
greater stimulation of the purine nucleotide cycle) and
may be a possible indicato r of training stress (Row-
bottom et al. 1997). This suggestion was based on
endurance training where uric acid was inversely cor-
related to endurance performance (Rowbottom et al.
1997). We recently reported that a moderate-intensity/
high-volume squat protocol resulted in significant in-
creases in resting uric acid concentrations for 4 days
into recovery and that carnitine supplementation
attenuated this response, presumably via increasing
blood flow (Volek et al. 2002). Interestingly, creatine
supplementation has been shown to increase limb
blood flow measured by venous occlusive plethys-
mography (Arciero et al. 2001). The importance of
creatine-induced effects on blood flow and biomarkers
for exercise stress in mediating adaptations to resis-
tance training warrants further investigation.
There were no changes in total cholesterol and tri-
glycerides, which is consistent with our prior work
(Volek et al. 2000). In contrast, creatine supplementa-
tion reduced triglycerides in subjects with moderate hy-
percholesteremia who maintained their habitual training
(Earnest et al. 1996) and improved HDL-cholestero l and
VLDL-cholesterol in healthy young athletic men who
performed a combination of resistance and sprint /agility
training (Kreider et al. 1998). As expected, there was a
significant increase in serum creatinine (within normal
ranges), which is consistent with prior work in healthy
men (Volek et al. 2000, 2001). As muscle creatine
breakdown has been shown to occur at a constant rate,
this small increase in creatinine is likely a result of the
larger muscle creatine stores after creatine supplemen-
tation. There were small but significant decreases in
hemoglobin and hematocrit, which may have been due
to increases in plasma volume. Alternatively, plasma
proteins and erythrocytes may be broken down to sup-
port protein anabolism during stressful training.
Hemolysis and subsequent reductions in blood hemo-
globin has been shown to occur in endurance athletes
but also during strength training as evidenced by
reductions in blood hemoglobin and haptoglobin
(Schobersberger et al. 1990).
In summary, the lack of correlation among the
changes in resting circulating hormones and perfor-
mance/body composition suggests that resting hormonal
concentrations do not explain the performance and body
composition responses to creatine supplementation
during short-term resistance training overreaching in
resistance-trained men. Our data do not, however, ad-
dress acute post-exercise endocrine responses to a
workout (i.e., those anabolic responses suggested to be
the primary mediators of tissue growth and repair fol-
lowing resistance exercise), 24-h hormonal fluctuations,
nor do they address hormone kinetics including poten-
tial affects at the level of synthesis/secretion, target tissue
receptor interaction, or degradation of hormones. The
increases in lean body mass with creatine supplementa-
tion are consistent with other resistance training studies.
Acknowledgements The authors would like to thank Michael
Robertson, Scott and Heather Mazzetti, Craig Bankowski, Lisa
Larkin, Cori Stahl, John Melish, Katie Baker, Rob Phares, Stacy
Peterson, and Patty Burns for their assistance in the personal
training of the subjects in this study. We kindly thank Twin Lab-
oratories (Hauppauge, N.Y.) for providing the supplements for this
study.
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