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Creatine-dextrose and protein-dextrose induce similar strength gains during training


Abstract and Figures

Creatine supplementation during resistance exercise training has been reported to induce greater increases in fat-free mass (FFM), muscle fiber area, and strength when compared with a placebo. We have recently shown that timing of nutrient delivery in the postexercise period can have positive effects on whole body protein turnover (B. D. Roy et al., Med Sci Sports Exerc. 32(8):1412-1418, 2000). We tested the hypothesis that a postexercise protein-carbohydrate supplement would result in similar increases in FFM, muscle fiber area, and strength as compared with creatine monohydrate (CM), during a supervised 2-month resistance exercise training program in untrained men. Young healthy male subjects were randomized to receive either CM and glucose (N = 11; CM 10 g + glucose 75 g [CR-CHO] (CELL-Tech)) or protein and glucose (N = 8; casein 10 g + glucose 75 g [PRO+CHO]), using double-blinded allocation. Participants performed 8 wk of whole body split-routine straight set weight training, 1 h.d(-1), 6 d.wk(-1). Measurements, pre- and post-training were made of fat-free mass (FFM; DEXA), total body mass, muscle fiber area, isokinetic knee extension strength (45 and 240 degrees.s(-1)), and 1 repetition maximal (1RM) strength for 16 weight training exercises. Total body mass increased more for CR-CHO (+4.3 kg, 5.4%) as compared with PRO-CHO (+1.9 kg, 2.4%) (P < 0.05 for interaction) and FFM increased after training (P < 0.01) but was not significantly different between the groups (CR-CHO = +4.0 kg, 6.4%; PRO-CHO = +2.6 kg, 4.1%) (P = 0.11 for interaction). Muscle fiber area increased similarly after training for both groups (approximately 20%; P < 0.05). Training resulted in an increase in 1RM for each of the 16 activities (range = 14.2-39.9%) (P < 0.001), isokinetic knee extension torque (P < 0.01), with no treatment effects upon any of the variables. We concluded that postexercise supplementation with PRO-CHO resulted in similar increases in strength after a resistance exercise training program as compared with CR-CHO. However, the greater gains in total mass for the CR-CHO group may have implications for sport-specific performance.
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Creatine-dextrose and protein-dextrose
induce similar strength gains during training
Departments of Medicine (Neurology and Neurological Rehabilitation) and Kinesiology, McMaster University, Hamilton,
Ontario, CANADA
dextrose and protein-dextrose induce similar strength gains during training. Med. Sci. Sports Exerc., Vol. 33, No. 12, 2001, pp.
2044–2052. Background: Creatine supplementation during resistance exercise training has been reported to induce greater increases
in fat-free mass (FFM), muscle fiber area, and strength when compared with a placebo. We have recently shown that timing of nutrient
delivery in the postexercise period can have positive effects on whole body protein turnover (B. D. Roy et al., Med Sci Sports Exerc.
32(8):1412–1418, 2000).Purpose: We tested the hypothesis that a postexercise protein-carbohydrate supplement would result in similar
increases in FFM, muscle fiber area, and strength as compared with creatine monohydrate (CM), during a supervised 2-month resistance
exercise training program in untrained men. Methods: Young healthy male subjects were randomized to receive either CM and glucose
(N11; CM 10 g glucose 75 g [CR-CHO] (CELL-Tech
)) or protein and glucose (N8; casein 10 g glucose 75 g
[PROCHO]), using double-blinded allocation. Participants performed 8 wk of whole body split-routine straight set weight training,
1 h·d
, 6 d·wk
. Measurements, pre- and post-training were made of fat-free mass (FFM; DEXA), total body mass, muscle fiber area,
isokinetic knee extension strength (45 and 240°·s
), and 1 repetition maximal (1RM) strength for 16 weight training exercises.
Results: Total body mass increased more for CR-CHO (4.3 kg, 5.4%) as compared with PRO-CHO (1.9 kg, 2.4%) (P0.05 for
interaction) and FFM increased after training (P0.01) but was not significantly different between the groups (CR-CHO ⫽⫹4.0 kg,
6.4%; PRO-CHO ⫽⫹2.6 kg, 4.1%) (P0.11 for interaction). Muscle fiber area increased similarly after training for both groups (~
20%; P0.05). Training resulted in an increase in 1RM for each of the 16 activities (range 14.2-39.9%) (P0.001), isokinetic
knee extension torque (P0.01), with no treatment effects upon any of the variables. Conclusions: We concluded that postexercise
supplementation with PRO-CHO resulted in similar increases in strength after a resistance exercise training program as compared with
CR-CHO. However, the greater gains in total mass for the CR-CHO group may have implications for sport-specific performance. Key
Creatine monohydrate supplementation has been
shown to increase the intramuscular total creatine
(TCr) and phosphocreatine (PCr) pools (~10-20%)
in humans (12,13). An elevated intramuscular PCr may
permit enhanced temporal buffering of ADP during high-
intensity muscular contractions (5,9), a reduction in neuro-
muscular fatigue (31), and thus allow for an increase in the
total number of contractions performed during strength
training (8,37). Given that one of the most potent stimuli for
increasing protein synthesis in skeletal muscle is muscle
contraction (21), a greater number of contractions over a
period of time may result in a greater cumulative stimulus
for protein synthesis and an increased net muscle protein
It has been consistently observed that an effect of acute
creatine ingestion (~20 g·d
5–10 d) is an increase of
between 1 and 2 kg in fat-free mass (FFM) (8,20,37). Most
of the increase is likely to be net water retention (12,13);
however, in the long-term, intracellular water retention,
resulting in cell swelling, could have positive effects upon
net protein retention (3). There is also in vitro evidence that
creatine can increase myosin specific protein synthesis
(14,15,38) and increase satellite cell mitotic activity during
muscle hypertrophy in a rat tenotomy model (7). Over a
period of time, an increase in myosin synthesis (assuming
no changes in protein breakdown) could promote an in-
crease in skeletal muscle protein.
It has been consistently reported that dietary supplemen-
tation with creatine monohydrate during a period of strength
training enhanced muscle mass and strength gains
(8,17,18,34,36). Each of these studies concluded that the
increase in FFM and strength was greater for the creatine-
supplemented group as compared with those who received
placebo (8,17,18,34,36). However, in most cases, the crea-
tine-supplemented group was not compared with a group
who received an isoenergetic and isonitrogenous “placebo”
(8,17,34,36). One study compared a combined creatine,
carbohydrate, and protein supplement with one containing
an isonitrogenous, but not isoenergetic, supplement contain-
ing protein and carbohydrate, and concluded that the FFM
gains during weight training were greater for the creatine
containing supplement (18).
Copyright © 2001 by the American College of Sports Medicine
Submitted for publication November 2000.
Accepted for publication March 2001.
The choice of the timing of nutrient delivery is also an
important consideration, for we and others have found that
the provision of glucose and amino acids in the postexercise
period enhanced aspects of protein metabolism that could
have significant effects upon FFM and strength gains
(26,33). Therefore, we chose an isoenergetic and isonitrog-
enous placeboand provided both supplements in the im-
mediate postexercise period to simulate the dietary practices
emerging from the results of studies showing a more posi-
tive protein balance when nutrients are consumed at that
time (25,32).
We hypothesized, a priori, that isoenergetic and isoni-
trogenous creatine-glucose and protein-glucose supple-
ments, consumed in the immediate postexercise period,
would be equivalent in their capacity to enhance the strength
and FFM gains after an 8-wk period of supervised strength
Subjects. Twenty-three young, healthy, male volun-
teers were recruited to participate in the study. Written
informed consent was obtained from each participant, and
the study was approved by the McMaster University Ethics
Committee. None of the participants were performing reg-
ular physical activity (2per week) at the start of the
study and had not done so for the preceding 6 months.
Before, and after, participation in the 8-wk exercise training
program (see below), all subjects completed 4-d diet records
(analyzed using Nutritionist V, First Data Bank, San Bruno,
CA) to develop a dietary checklist for each of the testing
sessions and to ensure that no subjects were vegans. The
physical and dietary characteristics of the subjects are pre-
sented in Table 1.
Experimental protocol. The participants were ran-
domized using a double-blind design to receive a commer-
cially available supplement containing creatine monohy-
drate and glucose (N12; ~ 308 kcal (assuming no energy
from creatine) 10-g creatine monohydrate; 75-g dextrose;
2-g taurine; 250-mg ascorbic acid; 300-
g chromium pico-
linate; 200-mg
-lipoic acid; 100-mg phosphorus; 150-mg
potassium; 60-mg sodium; 70-mg magnesium, and 20-mg
calcium [CR-CHO] (CELL-Tech
)), or protein and glucose
(N11; ~ 340 kcal 10-g caseinate; 75-g dextrose
[PRO-CHO]) after each exercise training session under di-
rect supervision of a research assistant (Table 2). The sup-
plements had identical grape flavoring and were mixed into
cold water and consumed within 30 min of exercise com-
pletion. The research assistant who supervised each session
mixed up the drinks and ensured that each drink was con-
sumed within 5 min. Because of the direct supervision,
compliance was 100% with supplement consumption on
five of the six exercise days. On one of the six exercise days,
the drink was mixed the night before and kept refrigerated
and was to be consumed within 30 min of exercise comple-
tion on the semisupervised day (see below). Compliance
was reported to be 100% by the subjects on this day.
After the first testing session, there were a total of three
subjects in the CR-CHO and one subject in the CR-CHO
group who dropped out of the study during the training
period for various personal reasons. Thus, there were a total
of 8 participants who completed all aspects of the training/
testing in the PRO-CHO group and 11 who completed all
aspects of the training/testing in the CR-CHO group. Each
subject completed 8 wk of supervised whole body split-
routine weight training, 1 h·d
, and completed
pre- and post-testing as described below.
Pre- and post-testing. Pre- and post-testing were
each conducted over an 8-d period. Before pretesting, each
subject completed three familiarization sessions under su-
pervision. Strength testing (one repetition maximal strength
(1RM)) was conducted over a 3-d period (days 1-3) for each
of 16 exercises. The legs were tested on the first day (leg
press, leg curl, leg extensions, standing calf raises), fol-
lowed by chest and back exercises (machine bench press,
latissimus pull-down, vertical bench press, seated narrow
low row, machine chest fly, seated machine wide-grip row),
and, finally, shoulder and arm exercises (seated machine
shoulder press, standing cable lateral raise, seated triceps
machine extension, seated biceps curl (preacher), standing
triceps extension (press-down) with angled bar, standing
biceps curl with cambered bar). Subjects initially performed
a warm-up set of 12 repetitions at approximately 50% of
their estimated 1RM, and a second preparatory set of three
repetitions at approximately 85% of estimated 1RM. The
first set was the first attempt at the predicted 1RM. A
successful lift was judged being through the full range of
motion of the exercise and was performed with proper
technique as assessed by an investigator. There was a 2-min
rest period between each successive attempt of a new 1RM.
If a subject could not lift the initial 1RM, the weight was
reduced accordingly and a 2-min rest period was provided
before the next 1RM attempt.
TABLE 1. Baseline subject characteristics.
CR-CHO (N11) PRO-CHO (N8) Significance
Age (yr) 23.9 2.9 23.5 3.4 NS
Height (cm) 175.6 8.3 177.4 7.1 NS
Body mass (kg) 76.1 25.2 76.8 9.0 NS
Body fat (%) 18.0 9.5 18.5 4.5 NS
Fat/bone free mass (kg) 57.8 11.4 59.9 8.5 NS
Results are mean SD; body fat and fat free mass were determined by DEXA scanning
(see text).
TABLE 2. Supplement composition.
(Cell-Tech) PRO-CHO
Energy intake (kcal) 308 340
Carbohydrate (dextrose) (g) 75 75
Protein (casein hydrolysate) (g) Nil 10
Nonmacronutrient contents
Creatine monohydrate (g) 10 Nil
Taurine (g) 2 Nil
Ascorbate (mg) 250 Nil
Chromium picolinate (
g) 300 Nil
-lipoic acid (mg) 200 Nil
Phosphorus, potassium (mg) 100, 150 Nil
Sodium, calcium, magnesium (mg) 60, 20, 70 Nil
The supplement was consumed under supervision within 30 min of completion of each
exercise session (6/7 dwk
CREATINE AND STRENGTH TRAINING Medicine & Science in Sports & Exercise
After the strength testing (day 4), subjects performed
strength and fatigue testing of the knee-extensors using an
isokinetic dynamometer (Biodex Medical Systems; System
3, Shirley, NY). Low-velocity (45°·s
) and high-velocity
) isokinetic torque were both assessed. The sub-
jects leg was strapped into the unit with Velcro
across the leg, chest, and lap, and leg length, seat height,
seat-back position, and seat position were recorded for sub-
sequent testing. Subjects performed one warm-up at each
velocity, and the second trial was recorded as their peak
power at the given velocity. After a 3-min rest period, a
fatigue test was performed consisting of 3 sets of 10 con-
tractions at 180°·s
with a 2-min rest period between each
set. Isokinetic strength/fatigue testing and 1RM strength
testing were performed pretraining, in the 5th week of
training and posttraining. Test-retest (2-5 d between ses-
sions) coefficients of variation for isokinetic strength were
2.4% (45°·s
) and 3.4% (240°·s
), and for 1RM testing
ranged from 0.8 to 5.3%.
For the next 3 days (days 57), subjects followed a
customized (isoenergetic and isonitrogenous with habitual
intake), flesh-free, checklist diet, performed no exercise,
and on day 8 an individual prepackaged diet was provided.
The day before biochemical testing (day 7), a 24-h urine
sample was collected, and in the evening body composition
(total body mass (TBM)), fat-free mass (FFM), and whole
body fat (body fat %)) were measured by dual energy x-ray
absorptiometry (DEXA; Model QDR-1000/W, Hologic
Inc., Waltham, MA) as previously described (20). The scans
were completed before and after supplementation at the
same time of the evening and 4 h after a defined light snack
(250 kcal, 60% carbohydrate). Whole body scans were
performed from head to toe in the single beam mode, and
bone mineral content (BMC), fat, and lean mass were cal-
culated using custom software (V 5.56, Hologic Inc.). FFM
was taken as BMC lean. All subjects were scanned with
their hands pronated at their sides and feet between 25 and
30 cm apart. The same investigator completed all of the
testing and recorded the subject position on the first trial to
ensure similar positioning for the subsequent trial. In a
previous reproducibility experiment, using the identical ma-
chine and with the same operator training program, it was
found that the coefficient of variation (CV) was 1.6, 1.4, and
1.8%, for whole body BMC, lean mass, and fat mass,
respectively, in 21 young female subjects (20.9 1.6 yr)
tested between 1 and 2 wk apart (6). From these data, it was
calculated that a sample size of 11 was sufficient to detect
a change in whole body lean mass of 2.0% (6). Given that
most acute creatine loading studies demonstrated increases
in mass of about 2.02.5% (5,8,20), we concluded a priori
that the power was adequate to avoid a type II statistical
error in the current study.
On day 8, the subjects arrived at the laboratory after
consuming 50% of their daily energy and nitrogen intake
provided as a prepackaged diet and performing no exercise.
A plastic catheter (20 Ga) was inserted into the antecubital
vein, and a blood sample was collected for plasma (heparin)
and serum (untreated) analysis of metabolites and enzymes
as outlined below. The serum sample was allowed to clot,
and the plasma sample blood was immediately centrifuged
at 1200 rpm and the plasma/serum were stored at 50°C
until subsequent analysis (see below). Subjects then per-
formed unilateral leg model weight exercise such that one
leg was exercised while the other remained in a resting state.
The dominant leg was exercised using 2 10 repetitions of
leg press at 80% of 1RM and 6 10 repetitions of leg
extension at 80% of 1RM. Each set was recorded and if the
subject was unable to complete 10 repetitions, the posttest-
ing protocol was modified to match the pretesting protocol.
Subjects were also infused with tracer doses of
alanine for 6 h after the exercise session for analysis of
protein turnover (data not reported in this study). The sub-
jects had a muscle biopsy of the vastus lateralis taken 2 h
after the exercise session from the nonexercised (rested) leg
using a suction modification. The sample was immediately
blotted and trimmed of any connective tissue if required.
One sample was quenched and stored in liquid nitrogen one
min after the sample was taken (29) for subsequent analysis
of phosphocreatine and creatine as previously described
(32). A second sample was mounted in optimal cutting
temperature (OCT) embedding medium that was prechilled
in isopentane cooled in liquid nitrogen, snap frozen, and
stored at 80°C until subsequent analysis (see below).
Exercise training. After the pretraining testing session,
subjects began a 6-d·wk
split-routine/straight set training
program lasting 8 wk (see below). Three workouts were
designed and performed twice per week (2 d of each of the
3 exercise types described above (legs, chest and back,
shoulder and arms)). All training sessions from Monday to
Friday were monitored by one of two of the investigators
(NY, CB) to ensure correct technique and compliance to the
workout intensity. Saturday training sessions were per-
formed without direct supervision; however, there was an
independent person verifying attendance at the training cen-
ter via a sign-in system. The order of the workouts was
staggered to prevent the same workout from falling on a
Saturday each week.
The program design utilized only machine exercises
(Badger Magnum, Milwaukee, WI) to ensure safety and to
reduce the learning curverequired by the subjects for
performance of the exercises. The exercise intensity was
initiated as approximately 80% of the predetermined 1 RM
for each exercise. In subsequent exercise sessions, the load
was adjusted to cause muscular failure within 612 repeti-
tions. The load was constantly adjusted between training
sessions to remain within the desired range of repetitions
and intensity.
The first three training sessions of week 1 were performed
for only 1 set of each exercise at the prescribed intensity.
The final three training sessions of week 1 were performed
for 2 sets of each exercise, and in weeks 28 there were 3
sets performed for each exercise. Every set was performed
to the point of muscular failure (fatigue). Training logs were
kept to record the volume and intensity of each workout.
Subjects were instructed not to engage in any new additional
exercise programs but were encouraged to continue with
Official Journal of the American College of Sports Medicine
their previous activity levels. All subjects performed 48
workouts with the exception of one person in each of the
groups who only completed 47 workouts between the pre-
and post-testing sessions.
Biochemical analyses. Plasma samples were ana-
lyzed for aspartate aminotransferase (AST) (intra-assay CV
9.1%), urea nitrogen (intra-assay CV 6.3%), and cre-
atinine (intra-assay CV 7.7%) by using kit assays (nos.
505, 640, and 555-A, respectively, Sigma, St. Louis, MO).
Creatine kinase activity (CK) was determined in serum
using a kit assay (no. DG147, Sigma) (intra-assay CV
6.1%). Urine was analyzed using the above creatinine (intra-
assay CV 7.2%) and urea (intra-assay CV 5.4%) kits
with appropriate dilutions for urine analyses.
Muscle samples frozen in liquid nitrogen were lyophi-
lized, powdered, and extracted in 0.5 M perchloric acid/1
mM EDTA and neutralized using 2 M KHCO
as previously
described (32). The extracts were analyzed for ATP, PCr,
and creatine by using an enzymatic method that has recently
been described in detail by our group (32). We found un-
usually low ATP and low PCr concentrations in about 50%
of the samples. It was subsequently discovered that some of
the samples had been left on a counter for up to 30 min
during a move of the laboratory. Thus, the ATP and PCr
values were of no use, and we shall only report the total
creatine values (given that partial thawing would increase
free creatine, decrease PCr, yet would not alter the total
creatine concentration due to the stoichiometry of the cre-
atine kinase reaction). The intra-assay CV was 3.7% for
total creatine.
Histochemical analysis. The OCT embedded biopsy
samples were serially sectioned (7
m thick) on a cryostat
microtome (Micron International, Walldorf, Germany) with
sample and cabinet temperatures at 20°C. Samples were
stained for myosin ATPase activity after preincubation at a
pH of 4.3, 4.6, and 10.1 using established methods (4), with
pre- and post-training cross-sectional samples assayed si-
multaneously. A total of 150500 fibers were available for
analysis from each subject. Fiber analyses were performed
using image analysis software (Image Pro Plus, Media Cy-
bernetics, Silver Springs, MD) interfaced with a microscope
(Olympus BX60, Melville, NY) and a digital camera (SPOT
Diagnostics Instruments, Inc., Sterling Heights, MI). We
used a custom MACRO program written within the image
analysis software to automatically calculate individual fiber
areas and to determine the percentage of each fiber type.
From this program, we determined the total number and area
of type I and II fibers at pH 4.3 and 10.1, respectively. The
program also allowed for the determination of the type I
fibers at pH 4.6, yet individual identification of the IIA and
IIB fibers had to be thresholded by the operator for each
slide. When the analysis of % total fiber area and mean fiber
area were tested for reproducibility, the intra-assay CVs
were 1.5% and 2.6%, respectively. When two serial sections
of the same muscle biopsy were tested for day to day
reproducibility of % total fiber area, and mean area of fibers
the interassay CVs were 2.4% and 1.3%, respectively.
Statistics. All data were analyzed using analysis of
variance (ANOVA) with a two-way split-plot design (be-
tween factor CR-CHO/PRO-CHO; within factor PRE/
POST training). Where appropriate, Tukey post hoc analysis
was employed to make pair-wise comparisons. Any power
calculations were performed using between-group compar-
isons with a two-tailed test,
0.05 and
0.20; N/group
, where Z Z-score, SD standard
deviation of the differences between the groups, and D
mean difference between the groups. Statistical significance
was considered to be at level P0.05. Statistical analysis
was performed using a computerized statistical package
(Statistica 5.1, Statsoft, Tulsa, OH).
Dietary analysis. There were no differences between
the groups in habitual energy intake or the percentage of
major macronutrients. Energy, carbohydrate, and protein
intake increased for the PRO-CHO group during the study
as compared with their habitual intake (P0.05); however,
during the 2-month trial, there were no differences between
the groups in terms of their habitual energy, protein, fat, and
carbohydrate intake (Table 3).
Anthropometry. There was a significant increase in
total body mass for both groups; however, the increase for
the CR-CHO group was greater (5.4%) as compared with
the PRO-CHO group (2.4%) (P0.05 for interaction).
Both groups increased FFM as a result of the training
program (P0.05), and there was a trend toward an
interaction between treatment and training (P0.11, two-
tailed; 0.055, one-tailed). A post hoc sample size calculation
revealed that 13 subjects/group would have been required to
detect a significant interaction between supplement and
training for FFM (see Statistics section). Fat mass was
reduced for the PRO-CHO group only after training (P
0.05 for interaction). The percentage of body fat was re-
duced similarly for both groups after training (P0.05). A
summary of the results is found in Table 4.
Muscle analyses. There were no differences in mus-
cle total creatine concentration between the groups before
TABLE 3. Diet analysis before and during training.
Pre (Habitual) During Study (8 wk)
Daily energy intake (kcal)
Cr-CHO 2858.5 792.8 2814.1 579.1
PRO-CHO 2673.5 708.3 3117.4 837.8*
Daily carbohydrate consumption (g)
Cr-CHO 353.4 114.9 381.6 94.8
PRO-CHO 334.6 97.2 418.2 92.8*
Daily fat consumption (g)
Cr-CHO 105.7 34.5 89.7 22.7
PRO-CHO 98.4 34.1 108.9 44.4
Daily protein consumption (g)
Cr-CHO 122.5 35.4 131.7 23.8
PRO-CHO 96.2 35.3 125.7 43.2*
Relative protein intake (gkg
Cr-CHO 1.60 0.58 1.64 0.45†
PRO-CHO 1.25 0.53 1.60 0.64†
Results are mean SD.
* Significant group time interaction (P0.05); symbol identifies significant
differences from pre training.
† Significant main effect for time (P0.05).
CREATINE AND STRENGTH TRAINING Medicine & Science in Sports & Exercise
training; however, the CR-CHO group had a higher total
creatine concentration after the training period as com-
pared with PRO-CHO (P0.05) (Table 5). There were
no between-group differences in the percentage area or
mean area for each of the major fiber types between the
groups before training. after the training program, there
were large increases in fiber areas of all fiber types that
were similar for both groups (P0.01). The data anal-
ysis was identical for each of the three major fiber types;
however, thresholding of the fiber density was difficult
for three of the Cr-CHO and two of the PRO-CHO
subjects at pH 4.6, and a full data set was available for the
total type I and II fibers.
Strength measurements. There were no between-
group differences in baseline 1RM strength for any of the 16
exercises listed in Table 2. There were significant increases
in 1RM strength for each of the exercises from pretesting to
that at 4 wk and 8 wk (post) (P0.01). There were no
treatment effects on the rate of increase in strength for any
of the 16 exercises (Table 6). In addition, there were sig-
nificant and similar increases for both groups in isokinetic
torque of the knee extensors at both slow (45°·s
) and fast
) contraction speeds from baseline to 4 wk and
from 4 wk to 8 wk of training (P0.05). The fatigue index
(F.I. % [maximum minimum]) was similar for both
groups before and after training across all three sets
(Table 7).
Plasma and urine analyses. Plasma AST activity
increased similarly for both groups after training but was
still within the normal range for age (P0.05). Serum CK
activity decreased similarly for both groups after training (P
0.05). There were no treatment or training effects upon
blood urea nitrogen concentration. Plasma creatinine con-
centration was higher for the CR-CHO group after training
but unchanged in the PRO-CHO group (P0.05 for in-
teraction). Twenty-four-hour urinary creatinine and urea N
excretion were not affected by either training or treatment
(Table 8).
Side effects. Two of the male subjects experienced a
transient, mild sense of abdominal discomfort on the CR-
CHO trial, and one reported a similar effect with the PRO-
CHO trial.
The main finding in the current study was that the
strength increases after 8 wk of strength training were iden-
tical for subjects who consumed a creatine/glucose supple-
ment (CR-CHO) as for those who consumed an isoenergetic
and isonitrogenous protein/glucose supplement (PRO-CHO)
postexercise. In spite of the similar increases in strength, the
increases in total body mass were higher for the CR-CHO as
compared with PRO-CHO group.
There have been four studies that have found greater
increases in strength for subjects who consumed creatine as
compared with a placebo during strength exercise training
(8,17,34,36). Differences in initial training status cannot
explain the differences as one study examined previously
untrained subjects (34), whereas the other studies used ei-
ther moderately trained (8,36), or highly trained athletes
(17). We specifically chose subjects who were untrained
because strength and lean mass increases would be expected
to be greater (1,19) as compared with already well-trained
athletes (8), and therefore a differential treatment effect
would be magnified. Clearly, the strength increases in spe-
cific weight exercises ranging from 14 to 40% in the current
study were significant, identical between groups and among
the highest increases reported to date for this duration of
training (2,19,28). Gender differences in the response to
creatine also cannot explain the different outcome in our
study as compared with the four previously mentioned, for
three studies had exclusively male (8,17,36), whereas the
other used exclusively female (34) subjects. Finally, a type
II statistical error (small sample size) is not a likely expla-
nation for the increases in strength that were observed,
because these were greater for the CR-CHO group in seven
of the exercises, greater for the PRO-CHO group in six of
the exercises, and identical for three of the testing exercises.
Therefore, the lack of a difference in strength increase
between the two treatment groups in our study is likely due
to the fact that strength training on either supplement re-
sulted in similar strength gains. In addition to the lack of a
treatment effect on the increases in movement specific
TABLE 4. Anthropometry measurements before and after training (DEXA).
Pre Post (8 wk) % Change
Total mass (kg)
CR-CHO 76.1 25.2 80.4 24.7*,5.4
PRO-CHO 76.8 9.1 78.7 7.8* 2.4
Fat/bone-free mass (kg)
CR-CHO 57.8 11.4 61.8 11.7* 6.4
PRO-CHO 59.9 8.4 62.5 7.8* 4.1
Fat mass (kg)
CR-CHO 15.6 15.0 15.7 14.8 0.6
PRO-CHO 14.2 3.9 13.4 3.15.6
% Fat
CR-CHO 18.0 9.5 17.3 9.2* 3.9
PRO-CHO 18.5 4.5 17.1 3.9* 7.5
Results are mean SD.
* Main effect for time (P0.05).
Significant group time interaction (P0.05).
TABLE 5. Muscle total creatine and muscle fiber characteristics.
Pre 8 wk % Change
Total creatine (mmolkg dry
CR-CHO 134.8 12.0 142.9 8.3* 6.0 3.5
PRO-CHO 125.6 6.3 124.1 7.0 1.1 2.3
Type Itotal area (%)
CR-CHO 33.5 7.4 33.8 12.6 1
PRO-CHO 35.8 13.3 36.1 13.8 1
Type IItotal area (%)
CR-CHO 66.5 7.3 66.1 12.1 1
PRO-CHO 64.1 13.3 63.8 13.8 1
Type Ifiber area (
CR-CHO 4318.3 943.7 5330.1 960.721.8 11.2
PRO-CHO 4652.7 868.9 5483.4 1617.117.4 18.7
Type IIfiber area (
CR-CHO 4743.0 830.4 5994.5 1077.425.0 20.4
PRO-CHO 5614.4 964.2 7238.3 1699.126.5 25.7
Results are mean SD.
* Significant interaction with CR-CHO showing an increase and no effect for
PRO-CHO (P0.05).
Type II fibers were significantly larger than type I (P0.05).
Main effect for training (P0.05).
Official Journal of the American College of Sports Medicine
strength, we also did not find an effect of treatment upon the
increases in isokinetic knee extension strength. Further-
more, we did not find any differences in the fatigue index
with repetitive knee extension isokinetic movements. This
latter finding supports the results of a previous study that did
not find an effect of creatine supplementation upon PCr
resynthesis (35). Alternatively, our lack of between-group
fatigue resistance in the isokinetic trials could indicate a lack
of statistical power due to the fact that only a subgroup of
individuals may show enhanced PCr resynthesis after sup-
plementation (10).
Another interesting observation was that similar increases
in strength occurred in spite of the higher concentration of
total creatine in the CR-CHO group as compared with the
PRO-CHO group. This did show that the treatment was
effective in increasing the total creatine content. It could be
argued that although total creatine content was increased,
we were not able to show an increase in phosphocreatine,
due to technical reasons described above. However, in the
training study performed by Volek and colleagues (36),
neither the total nor phospho-creatine concentration in skel-
etal muscle were higher at 12 wk for those who were
supplemented with creatine, yet they demonstrated that both
performance and FFM increases were greater for CR versus
One of the reasons that may explain the differing results
between our study and previous work (8,17,34,36) is that the
dietary interventions in these studies were not designed to
provide similar energy contents. For example, in these stud-
ies the placebowas either cellulose (36), maltodextrin
(34), or glucose (8). In another study, the placebo and
creatine supplements each contained 99 g of glucose,3gof
taurine, and ~ 1.1 g each of sodium and potassium phos-
phate with the creatine group also getting an additional
TABLE 6. 1RM measurements before and after training.
Pre 4 wk 8 wk
% Change
(Pre-8 wk)
Shoulder press
CR-CHO 163 36 182 45* 203 5620
PRO-CHO 169 47 183 50* 197 5414
Lateral raise
CR-CHO 39 84810* 55 1229
PRO-CHO 39 95312* 56 1030
Bench press
CR-CHO 160 52 176 46* 192 4517
PRO-CHO 145 43 158 48* 175 4617
Vertical bench press
CR-CHO 192 51 225 55* 254 5924
PRO-CHO 175 45 206 55* 229 6724
Chest flys
CR-CHO 170 37 233 39* 257 4534
PRO-CHO 166 56 220 61* 239 6431
Lattissimus pull-down
CR-CHO 133 16 158 25* 167 2520
PRO-CHO 132 29 161 34* 175 3225
Wide row
CR-CHO 109 17 140 27* 156 3630
PRO-CHO 109 22 144 33* 161 3332
Narrow row (seated)
CR-CHO 127 16 155 21* 167 2524
PRO-CHO 130 29 158 29* 172 3124
Bicep curl (standing)
CR-CHO 126 24 160 34* 174 3928
PRO-CHO 125 37 156 41* 166 4625
Arm curl (preacher)
CR-CHO 113 23 134 28* 148 3124
PRO-CHO 113 39 136 39* 151 4625
Tricep press-down
CR-CHO 129 25 167 35* 184 4430
PRO-CHO 123 29 152 32* 163 4025
Tricep extension
CR-CHO 87 19 116 25* 126 2631
PRO-CHO 88 23 105 35* 113 3522
Leg press
CR-CHO 511 128 640 133* 724 13629
PRO-CHO 523 134 641 124* 724 14528
Leg curl
CR-CHO 125 24 169 44* 187 5333
PRO-CHO 128 35 169 42* 193 5534
Leg extension
CR-CHO 217 64 285 83* 337 9236
PRO-CHO 228 92 288 84* 339 10133
Leg calf raise
CR-CHO 131 33 177 35* 199 4234
PRO-CHO 125 54 188 52* 209 5840
Results are mean SD; values are in pounds.
* Significant increase from pre (P0.01).
Significant increase from 4 wk (P0.01).
CREATINE AND STRENGTH TRAINING Medicine & Science in Sports & Exercise
15.75 g of CM (17). One study compared several different
nutritional supplements (maltodextrin 190 g·d
(PL); 290 g
60 g protein·d
(GF); and 64 g car-
bohydrate/d 67 g protein·d
20 g creatine·d
taurine and glutamine)(P)) during 28 d of resistance training
in young men (18). They concluded that GF and P were
superior in terms of total mass accretion compared with PL
and that P was superior in terms of FFM accretion (18).
Unfortunately, the energy content between the supplements
in the latter study varied substantially (18), which limited
the interpretation regarding an effect of energy and/or com-
position. In the current study, we compared supplements
with nearly identical amounts of energy, with creatine and
casein protein hydrolysate being the major difference be-
tween the groups. In the CR-CHO group, there were also
some minor compounds present (i.e., taurine), which, in the
amounts found, have not been shown to have a direct in-
fluence upon the outcome variables examined in the current
study. For example, taurine (present in the highest quantity
in our study) was present in higher concentrations in the
supplements used in one study (17) where the effects of
creatine and training upon FFM and strength were similar to
the three other studies in which the supplements did not
contain taurine (8,34,36). Furthermore, the timing of inges-
tion of the supplement with respect to the training sessions
has not been optimized in the latter studies (8,17,34,36). We
have shown that immediate postexercise glucose supple-
ments can reduce myofibrillar protein breakdown (26) and
enhance muscle glycogen resynthesis (25), and others have
shown that amino acid (33) and amino acid-glucose (24)
supplements can enhance net protein balance, after strength
exercise. It is also advantageous to consume creatine with
glucose in the postexercise period because insulin (30) and
muscle contraction (12) can stimulate creatine uptake into
skeletal muscle. For these reasons, and because most ath-
letes consume some nutrition and/or supplement during or
after exercise, we chose to compare a creatine/carbohydrate
supplement to a protein/carbohydrate supplement provided
in the immediate postexercise period.
A finding that also supports our observation of no differ-
ences in strength gains between the two supplements was
the finding of identical increases in muscle fiber diameter in
the current study. An earlier study found that a creatine-
supplemented group had greater increases in fiber diameter
after training as compared with a group who consumed a
placebo (36). Careful examination of the data revealed that
the diameter of the muscle fibers were 21.9% smaller (range
12.627%) for the creatine as compared with placebo sup-
plemented group at baseline before training and that after
training there was no difference in the fiber areas (36). Our
findings do show that after strength training there were no
differences in muscle fiber area between persons who con-
sumed creatine and carbohydrates as compared with those
who consumed protein and carbohydrates and that when
initial fiber areas are similar, the increase as a result of
training is similar for either CR-CHO or PRO-CHO.
A somewhat surprising finding was that although the
increase in strength and muscle fiber areas were identical
between the groups, the total mass for the CR-CHO group
was greater than for the PRO-CHO group. Although there
was a trend toward a greater increase in fat-free mass for the
CR-CHO group, this was not statistically significant (P
0.11). The maintenance of fat mass for the CR-CHO group
and the significant decrease in fat for the PRO-CHO group
can explain 37.5% of the difference between the groups in
total mass. If we assume that the trend for an increase in
FFM (paralleling the increase in total mass) is true, then
there are two hypotheses to explain this phenomenon. First,
the increase is due to higher total body water content. If
creatine does function as an osmolyte and draws water into
the cell (13), then the increase in weight could be total body
water. We did show a higher total muscle creatine content
for those who supplemented with creatine, which, in com-
bination with the fact that most of the bodys total creatine
is found in skeletal muscle (11,12), would fit the hypothesis
presented. Although an increase in muscle cell diameter
would be expected with an increase in myofibrillar water,
the absolute difference between the groups in lean mass
TABLE 7. Torque/fatigue measurements of the leg extensors before and
after training.
Speed/Group Pre 4 wk 8 wk
CR-CHO 219.6 48.2 233.2 44.8* 235.3 49.3
PRO-CHO 241.8 45.7 258.4 69.2* 260.9 62.5
CR-CHO 145.8 32.4 156.5 31.7* 162.4 31.3
PRO-CHO 157.5 27.7 164.7 26.6* 181.4 25.9
F.I. Set 1 (%)
CR-CHO 16.6 6.1 14.5 5.0
PRO-CHO 19.0 6.7 17.5 5.1
F.I. Set 2 (%)
CR-CHO 19.5 6.4 18.5 3.8
PRO-CHO 19.9 6.4 21.7 4.9
F.I. Set 3 (%)
CR-CHO 20.7 10.4 19.7 8.3
PRO-CHO 21.9 5.4 20.3 6.0
Results are means SD.
* Significant increase from pre values N (P0.05).
Significant increase from 4 wk (P0.05).
F.I., fatigue index, 10 repetitions at 180°s
(see text).
TABLE 8. Plasma and urine measurements before and after training.
Pre Post (8 wk)
CR-CHO 14.5 5.3 17.4 6.4*
PRO-CHO 16.7 5.8 18.1 6.3*
CR-CHO 61.2 16.9 40.0 21.2*
PRO-CHO 78.0 35.8 41.7 16.7*
Urea N (mgdL
CR-CHO 19.2 4.8 21.9 7.5
PRO-CHO 17.4 6.2 15.2 3.5
Creatinine (
CR-CHO 100.5 27.1 122.1 30.3*,
PRO-CHO 99.9 21.9 103.5 33.5*
Urinary urea N (g24 h
CR-CHO 9.66 6.5 10.1 5.4
PRO-CHO 10.3 2.1 9.2 3.9
Urinary creatinine (g24 h
CR-CHO 1.38 0.67 1.86 0.77
PRO-CHO 1.47 0.33 1.51 0.49
Results are mean SD.
* Significant main effect for training.
Significant Group time interaction (P0.05).
Official Journal of the American College of Sports Medicine
accretion was 1.4 kg, and, assuming that a 75-kg male has
30 kg of muscle mass, this amounts to a 4.7% increase in
muscle water mass (assuming that all the water is intracel-
lular), and the resultant area changes may not be detectable
with histochemical techniques. Alternatively, but not to the
mutual exclusivity of the aforementioned hypothesis, there
could be a greater increase in total creatine, hence, an
increase in volume of nonskeletal muscle tissues. The locus
of this is unclear as creatine transporters are found predom-
inantly in skeletal muscle, heart, kidney, and brain (11),
although creatine transporter mRNA is also found in liver
(27) and intestine (16). From a practical standpoint for the
athlete, it may be that those who participate in sports where
a high strength:lean mass ratio is important (i.e., wrestling,
jumping) should consider the PRO-CHO postexercise nu-
trition, whereas those in which a high absolute mass is
required (i.e., American football) could consider a creatine-
carbohydrate supplement (ignoring, for sake of argument,
any potential ethical issues in sport).
Finally, we found that the creatine-carbohydrate and pro-
tein-carbohydrate supplements were well tolerated by the
subjects with only minor abdominal discomfort reported in
two and one subject(s), respectively. From a biochemical
standpoint, we found a small but significant increase in
aspartate amino transferase activity for both groups after
exercise, with the values still being in the normal range.
Creatine kinase activity was slightly lower after exercise
training with no effect of supplementation, which was con-
sistent with an earlier report by our group after acute crea-
tine monohydrate supplementation (20). Plasma creatinine
concentration did increase to a greater extent for the creat-
ine-supplemented group after training, which was identical
to the findings of another study using highly trained football
players (17). As we and others have demonstrated, an in-
crease in creatinine in the plasma represents an increase in
the rate of appearance of creatinine to the nephron and
creatinine clearance is unchanged after acute (20,22) and
long-term (23) creatine supplementation.
In summary, we have shown that the provision of protein-
carbohydrate supplements in the postexercise period results
in similar increases in strength and muscle fiber area as
compared with a creatine-carbohydrate supplement after a
period of strength training. The increases in total mass were
greater for the creatine-carbohydrate supplement. Both sup-
plements were well tolerated. There may be sport-specific
supplement recommendations from these results.
This research was supported by MuscleTech Research and De-
velopment and Hamilton Health Sciences Department of Rehabili-
tation. Thanks to John Stein for help during data collection.
Address for correspondence: Dr. M. Tarnopolsky, Dept. of Neu-
rology, Rm. 4U4, McMaster University Medical Center, 1200 Main
St. W., Hamilton, Ontario, Canada, L8N 3Z5; E-mail: tarnopol@
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... Bibliografía: [108][109][110][111][112][113][114][115][116] Tópicos en nutrición y suplementación deportiva -Dr. Heber E. Andrada pág. ...
... Tópicos en nutrición y suplementación deportiva -Dr. Heber E. Andrada pág.114 ...
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This book is intended for anyone passionate about nutrition and sports supplementation. It aims to introduce readers to what regards the subject, combining areas such as nutrition, biological chemistry, the physiology of the exercise, food science and pharmacology. It is by no means intended to replace a good book on each of these areas, just try to give a general snapshot of each of the substances that are currently being used in the world of supplementation sports, its functions, applications, benefits and doses that are usually used. Heber E. Andrada October 5, 2020
... A suplementação de CR também está associada a um aumento inicial de peso, possivelmente devido à retenção de água relacionada à captação de CR pelo músculo. No entanto, esse ganho de peso inicial pode estar relacionado a um aumento subsequente na força muscular, que pode ser atribuído a um maior volume e intensidade de treinamento alcançado com a suplementação de CR (Tarnopolsky et al., 2001). Engelhardt et al. (1998) avaliaram os efeitos da suplementação de nas concentrações de creatina e creatinina em atletas. ...
Full-text available
Nutritional supplements integrated with any physical or sports activity are substances aimed at increasing physical performance, improving physical effort efficiency, enhancing physical recovery processes after intense exertion, enhancing training quality, and facilitating physiological adaptations. Among the most commonly used supplements is creatine (CR), a non-essential nitrogenous compound formed by three amino acids: glycine, arginine, and methionine, whose main benefit lies in improving performance in high-intensity activities. The consumption of CR along with carbohydrate (CHO) sources promotes supplement absorption compared to isolated consumption due to increased plasma insulin levels. The human body can absorb approximately 25% more CR when ingested with a CHO source. This review aimed to provide an expanded outlook on the consumption of CR combined with CHO sources and its relationship with increased CR transport into muscle cells in individuals engaging in strength exercises. Studies have shown that the increase or improvement in CR absorption by muscle cells may be related to increased blood glucose levels and consequent insulin release, which acts in a co-dependent and direct manner on the membrane transporter that regulates the entry of CR together with sodium into the intracellular environment, demonstrating that CHO supplementation is not necessary every time CR is consumed, but instead that this improvement consists of increased serum glucose and insulin release.
... Whey protein (WP) and creatine monohydrate (CrM) are the two dietary supplements commonly used to promote muscle strength and hypertrophy [1][2][3][4]. WP is acid soluble and thus digested quickly. WP contain enriched essential amino acids, including branched chain amino acids (BCAA) that the body needs for tissue synthesis, energy, and health. ...
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The present study examined the effect of simultaneous ingestion of whey protein (WP) and creating monohydrate (CrM) on body composition, selected measures of muscular strength and power, and risks for potential renal dysfunction. Fifteen professional athletes including nine males and six females specialized in track and field, Olympic weight lifting, and modern pentathlon volunteered to participate in the study. Subjects underwent a four-week treatment period during which they ingested both (WP) and CrM while maintaining their regular diet and training intensity and volume. Body composition and performance of one-min pull-up, one-min push up, one-min squat-to-stand, standing long jump, triple jump, and 30-s single leg lateral jumps were measured before and after the treatment. Urine samples were collected throughout the treatment to determine albumin and creatinine concentrations. No changes in body weight, muscle mass, and % body fat were noted following the treatment. The treatment, however, improved (p < 0.05) scores in one-min pull-up, one-min push up, one-min squat-to-stand, triple jump, 30-s single leg lateral jump tests. No differences in urinary albumin and creatinine were found throughout the treatment period. In conclusion, co-supplementation of WP and CrM for four weeks is an effective yet safe ergogenic strategy in enhancing strength and power in professional athletes.
... In support of this theory, Esmarck and coworkers [107] found that ingesting carbohydrate and protein immediately following exercise doubled training adaptations in comparison to waiting until 2-hours to ingest carbohydrate and protein. Additionally, Tarnopolsky and associates [430] reported that post-exercise ingestion of carbohydrate with protein promoted as much strength gains as ingesting creatine with carbohydrate during training. A recent study by Kreider and colleagues [431] found that protein and carbohydrate supplementation post workout was capable of positively supporting the post exercise anabolic response. ...
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Abstract Sport nutrition is a constantly evolving field with literally thousands of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper presents a well-referenced overview of the current state of the science related to how to optimize training through nutrition. More specifically, this article discusses: 1.) how to evaluate the scientific merit of nutritional supplements; 2.) general nutritional strategies to optimize performance and enhance recovery; and, 3.) our current understanding of the available science behind weight gain, weight loss, and performance enhancement supplements. Our hope is that ISSN members find this review useful in their daily practice and consultation with their clients.
Full-text available
In 2011, we published a paper providing an overview about the bioavailability, efficacy, and regulatory status of creatine monohydrate (CrM), as well as other “novel forms” of creatine that were being marketed at the time. This paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM, and that CrM was recognized by international regulatory authorities as safe for use in dietary supplements. Moreover, that most purported “forms” of creatine that were being marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy. We also provided examples of several “forms” of creatine that were being marketed that were not bioavailable sources of creatine or less effective than CrM in comparative effectiveness trials. We had hoped that this paper would encourage supplement manufacturers to use CrM in dietary supplements given the overwhelming efficacy and safety profile. Alternatively, encourage them to conduct research to show their purported “form” of creatine was a bioavailable, effective, and safe source of creatine before making unsubstantiated claims of greater efficacy and/or safety than CrM. Unfortunately, unsupported misrepresentations about the effectiveness and safety of various “forms” of creatine have continued. The purpose of this critical review is to: (1) provide an overview of the physiochemical properties, bioavailability, and safety of CrM; (2) describe the data needed to substantiate claims that a “novel form” of creatine is a bioavailable, effective, and safe source of creatine; (3) examine whether other marketed sources of creatine are more effective sources of creatine than CrM; (4) provide an update about the regulatory status of CrM and other purported sources of creatine sold as dietary supplements; and (5) provide guidance regarding the type of research needed to validate that a purported “new form” of creatine is a bioavailable, effective and safe source of creatine for dietary supplements. Based on this analysis, we categorized forms of creatine that are being sold as dietary supplements as either having strong, some, or no evidence of bioavailability and safety. As will be seen, CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety. Additionally, CrM is the source of creatine recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.
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Context The impact of timing the consumption of protein supplements in relation to meals on resistance training–induced changes in body composition has not been evaluated systematically. Objective The aim of this systematic review was to assess the effect of consuming protein supplements with meals, vs between meals, on resistance training–induced body composition changes in adults. Data Sources Studies published up to 2017 were identified with the PubMed, Scopus, Cochrane, and CINAHL databases. Data Extraction Two researchers independently screened 2077 abstracts for eligible randomized controlled trials of parallel design that prescribed a protein supplement and measured changes in body composition for a period of 6 weeks or more. Results In total, 34 randomized controlled trials with 59 intervention groups were included and qualitatively assessed. Of the intervention groups designated as consuming protein supplements with meals (n = 16) vs between meals (n = 43), 56% vs 72% showed an increase in body mass, 94% vs 90% showed an increase in lean mass, 87% vs 59% showed a reduction in fat mass, and 100% vs 84% showed an increase in the ratio of lean mass to fat mass over time, respectively. Conclusions Concurrently with resistance training, consuming protein supplements with meals, rather than between meals, may more effectively promote weight control and reduce fat mass without influencing improvements in lean mass.
Few supplement combinations that are marketed to athletes are supported by scientific evidence of their effectiveness. Under the rigor of scientific investigation, we often see that the patented combination fails to provide any greater benefit when compared to an active (generic) ingredient. The focus of this chapter is supplement combinations and dosing strategies that are effective at promoting an acute physiological response that may improve/enhance exercise performance and/or influence chronic adaptations desired from training. In recent years, there has been a particular focus on two nutrition ergogenic aids—creatine monohydrate and protein/amino acids—in combination with specific nutrients in an effort to augment or add to their already established independent ergogenic effects. These combinations and others are discussed in this chapter.
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To investigate the effect of acute changes of extracellular osmolality on whole body protein and glucose metabolism, we studied 10 male subjects during three conditions: hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl [2-5%; (wt/vol)] during 17 h; hypoosmolality was produced by intravenous administration of desmopressin, liberal water drinking, and infusion of hypotonic saline (0.4%); and the isoosmolality study consisted of ad libitum oral water intake by the subjects. Leucine flux ([1-13C]leucine infusion technique), a parameter of whole body protein breakdown, decreased during the hypoosmolality study ( P < 0.02 vs. isoosmolality). The leucine oxidation rate decreased during the hypoosmolality study ( P < 0.005 vs. isoosmolality). Metabolic clearance rate of glucose during hyperinsulinemic-euglycemic clamping increased less during the hypoosmolality study than during the isoosmolality study ( P < 0.04). Plasma insulin decreased, and plasma nonesterified fatty acids, glycerol, and ketone body concentrations and lipid oxidation increased during the hypoosmolality study. It is concluded that acute alterations of plasma osmolality influence whole body protein, glucose, and lipid metabolism; hypoosmolality results in protein sparing associated with increased lipolysis and lipid oxidation and impaired insulin sensitivity.
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This randomized double-blind cross-over study assessed protein (PRO) requirements during the early stages of intensive bodybuilding training and determined whether supplemental PRO intake (PROIN) enhanced muscle mass/strength gains. Twelve men [22.4 +/- 2.4 (SD) yr] received an isoenergetic PRO (total PROIN 2.62 or carbohydrate (CHO; total PROIN 1.35 supplement for 1 mo each during intensive (1.5 h/day, 6 days/wk) weight training. On the basis of 3-day nitrogen balance (NBAL) measurements after 3.5 wk on each treatment (8.9 +/- 4.2 and -3.4 +/- 1.9 g N/day, respectively), the PROIN necessary for zero NBAL (requirement) was 1.4-1.5 The recommended intake (requirement + 2 SD) was 1.6-1.7 However, strength (voluntary and electrically evoked) and muscle mass [density, creatinine excretion, muscle area (computer axial tomography scan), and biceps N content] gains were not different between diet treatments. These data indicate that, during the early stages of intensive bodybuilding training, PRO needs are approximately 100% greater than current recommendations but that PROIN increases from 1.35 to 2.62 do not enhance muscle mass/strength gains, at least during the 1st mo of training. Whether differential gains would occur with longer training remains to be determined.
Purpose: The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle creatine accumulation. Methods: Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine (N = 10) or placebo (N = 9) group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training. Results: After 12 wk, significant (P < or = 0.05) increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported. Conclusion: Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training, presumably mediated via higher quality training sessions.
Several neuromuscular disorders are associated with reductions in intramuscular adenosine triphosphate (ATP) and/or phosphocreatine (PCr). These alterations have been primarily characterized using 31P–magnetic resonance spectroscopy (31P-MRS). We prospectively measured total creatine, PCr, and ATP in muscle biopsies from 81 patients: normal controls (n = 33), mitochondrial cytopathy (n = 8), neuropathic (n = 3), dystrophy/congenital myopathies (n = 7), inflammatory myopathy (n = 12), and miscellaneous myopathies (n = 18) using direct biochemical analysis. Intramuscular concentrations of PCr and ATP were lower for the dystrophy/congenital myopathy, inflammatory myopathy, and mitochondrial disease patients with ragged red fiber (RRF) as compared with normal controls (P < 0.05). Total creatine was lower for the dystrophy/congenital myopathy group as compared with the normal control group (P < 0.05). These values compare favorably to results from other studies using 31P-MRS and provide external validation for the values obtained using that method. Given the reductions in high-energy phosphate compounds in these patients, there is the potential for therapeutic intervention with creatine monohydrate supplementation. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1228–1233, 1999.
Creatine and creatine phosphate act as a buffer system for the regeneration of ATP in tissues with fluctuating energy demands. Following reports of the cloning of a creatine transporter in rat, rabbit, and human, we cloned and sequenced a creatine transporter from a human intestinal cDNA library. PCR amplification of genomic DNAs from somatic cell hybrid panels localized two creatine transporter (CT) genes: CT1 to Xq26-q28 and CT2 to 16p11.2. Refinement of CT1 to Xq28 was confirmed by FISH. Identification of CT2 sequences in YACs and cosmid contigs that had been ordered on human chromosome 16 enabled its assignment to the proximal end of 16p11.2. Sequencing of the CT2 gene identified sequence differences between CT1 and CT2 transcripts that were utilized to determine that CT2 is expressed in testis only. CT2 is the most proximally identified gene on chromosome 16p to date. The existence of an autosomal, testis-specific form of the human creatine transporter gene suggests that creatine transporter activity is critical for normal function of spermatazoa following meiosis.
The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K+]0 = 4.0 mM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical observation that PA may exert both artiarrhythmic and arrhythmogenic effects. The primary mechanism by which PA modifies excitability would seem to differ considerably from that of the structurally similar local anesthetic agent lidocaine.
The observation that increased muscular activity leads to muscle hypertrophy is well known, but identification of the biochemical and physiological mechanisms by which this occurs remains an important problem. The hypothesis has been proposed that creatine, an end product of contraction, may be the chemical signal coupling increased muscular activity and increased contractile mass. Two muscle models have been used in experimental tests of this hypothesis: differentiating skeletal muscle cells in culture and the fetal mouse heart in organ culture. Using these culture models, it is possible to alter the intracellular creatine concentration and to measure the effect of increased creatine concentrations on the rates of synthesis and accumulation of both muscle-specific and nonspecific proteins. The results show that muscle-specific protein synthesis in both skeletal and cardiac muscle is selectively stimulated by creatine.
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.
The concentrations of ATP, phosphocreatine (PCr), creatine, and lactate were determined in muscle biopsy samples frozen immediately or after a delay of 1-6 min. During the delay the samples were exposed to normal air or a gas mixture of 6.5% CO2-93.5% O2. The ATP content was unchanged, but PCr increased significantly from 72 mmol after rapid freezing to 85 mmol X kg dry muscle-1 during the 1st min in air. The lactate concentration increased (2.8 to 5.2 mmol X kg-1). If muscles were made anoxic by circulatory occlusion for 4-6 min before sampling, no increase in PCr was observed. Direct homogenization of fresh tissue in perchloric acid gave the same ATP, PCr, and lactate contents as frozen samples. It is concluded that the ATP and PCr contents in muscle are unaffected by freezing but that the biopsy procedure activates the energy utilization processes resulting in PCr decrease. It is suggested that the muscle PCr content after a 1-min delay in tissue freezing corresponds to the level in resting fresh muscle.