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Previous research has indicated that creatine retention is influenced by intramuscular creatine concentration and extracellular concentrations of glucose and insulin. This study examined whether different nutritional strategies affect whole body creatine retention. Specifically, 16 males with no history of creatine supplementation participated in this study. Subjects donated 24-hr urine samples for 4 days. After an initial control day, subjects were matched according to body mass and assigned to ingest in a single blind manner either 5 g of dextrose (D), 5 g of creatine monohydrate (CM), 5 g of CM + 18 g dextrose (C+D), or an effervescent creatine (EC) supplement (5 g of creatine + 18 g dextrose + 320 mg of sodium [as sodium carbonate and bicarbonate] + 175 mg of potassium [as potassium bicarbonate]) four times/day for 3 days. Creatine retention was estimated by subtracting total urinary creatine excretion from total supplemental creatine intake over the 3 day period. Data were analyzed by ANOVA. Results revealed that creatine retention was increased following creatine supplementation in all groups (D=0±0; CM= 36.6±9; C+D=48.0±7; EC=37.8±8 g, p=0.001). However, creatine retention in the C+D group was significantly greater than the CM group while no differences were observed between the EC and CM groups. This resulted in a greater percentage of creatine retention in the CD group (D= 0±0; CM=61±15; C+D=80±11; EC=63±13 %, p=0.001). These preliminary findings suggest that in accordance with previous research, ingesting dextrose (18 g) with CM (5 g) augments whole body creatine retention while EC supplementation appears to be no more effective than ingesting CM alone.
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Creatine Retention Following 3 Formulations of Creatine Ingestion
37
JEPonline
Journal of Exercise Physiologyonline
Official Journal of The American
Society of Exercise Physiologists (ASEP)
ISSN 1097-9751
An International Electronic Journal
Volume 6 Number 2 May 2003
Nutrition and Exercise
DIFFERENCES IN CREATINE RETENTION AMONG THREE NUTRITIONAL
FORMULATIONS OF ORAL CREATINE SUPPLEMENTS
MIKE GREENWOOD, RICHARD KREIDER, CONRAD EARNEST, CHRISTOPHER RASMUSSEN,
ANTHONY ALMADA
Sport & Exercise Nutrition Laboratory, Center for Exercise, Nutrition & Preventive Health Research
Department of Health, Human Performance & Recreation, Baylor University, Waco, Texas
ABSTRACT
DIFFERENCES IN CREATINE RETENTION AMONG THREE NUTRITIONAL FORMULATIONS OF
ORAL CREATINE SUPPLEMENTS. Mike Greenwood, Richard Kreider, Conrad Earnest, Christopher
Rasmussen, Anthony Almada. JEPonline. 2003;6(2):37-43. Previous research has indicated that creatine
retention is influenced by intramuscular creatine concentration and extracellular concentrations of glucose and
insulin. This study examined whether different nutritional strategies affect whole body creatine retention.
Specifically, 16 males with no history of creatine supplementation participated in this study. Subjects donated
24-hr urine samples for 4 days. After an initial control day, subjects were matched according to body mass and
assigned to ingest in a single blind manner either 5 g of dextrose (D), 5 g of creatine monohydrate (CM), 5 g of
CM + 18 g dextrose (C+D), or an effervescent creatine (EC) supplement (5 g of creatine + 18 g dextrose + 320
mg of sodium [as sodium carbonate and bicarbonate] + 175 mg of potassium [as potassium bicarbonate]) four
times/day for 3 days. Creatine retention was estimated by subtracting total urinary creatine excretion from total
supplemental creatine intake over the 3 day period. Data were analyzed by ANOVA. Results revealed that
creatine retention was increased following creatine supplementation in all groups (D=0±0; CM= 36.6±9;
C+D=48.0±7; EC=37.8±8 g, p=0.001). However, creatine retention in the C+D group was significantly greater
than the CM group while no differences were observed between the EC and CM groups. This resulted in a
greater percentage of creatine retention in the CD group (D= 0±0; CM=61±15; C+D=80±11; EC=63±13 %,
p=0.001). These preliminary findings suggest that in accordance with previous research, ingesting dextrose (18
g) with CM (5 g) augments whole body creatine retention while EC supplementation appears to be no more
effective than ingesting CM alone.
Key Words: Exercise, Sport Nutrition, Dietary Supplementation, Ergogenic Aid
INTRODUCTION
Creatine Retention Following 3 Formulations of Creatine Ingestion
38
Creatine supplementation (5 g taken 4 times/day) has been reported to increase muscle creatine and phosphocreatine
content by 5 to 30%. However, a significant amount of intra-subject variability has been reported in the literature
regarding the magnitude that creatine stores are increased in response to creatine loading and how elevations in
muscle creatine content affect performance (1). Research on the variability in creatine retention has indicated that
creatine uptake into the muscle is influenced by the amount of creatine in the muscle before supplementation, as well
as glucose-stimulated increased insulin release (2,3). In this regard, studies have suggested that co-ingestion of
creatine with large amounts of glucose (97 g) and/or combinations of glucose and protein may enhance creatine
storage (2-5). Consequently, it has been proposed that creatine storage may be glucose and/or insulin dependent (6).
Theoretically, co-ingestion of creatine with other nutrients that have been reported to affect insulin sensitivity and/or
glucose availability may enhance creatine retention (7).
Over the last few years, a number of creatine containing products have been marketed with claims to enhance creatine
transport into muscle. Most of these contain glucose with other nutrients designed to optimize cell volume and/or
transport creatine or glucose (e.g., taurine, glutamine, etc). Additionally, several different forms of creatine have
been marketed (liquid, candy, gum, effervescent, creatine citrate, etc). For example, effervescent creatine citrate
products have been marketed as a more optimal means of ingesting creatine because they theoretically enhance the
suspension and solubility of the creatine in liquid, optimize pH levels to prevent degradation of creatine to creatinine,
and reduce purported gastrointestinal problems that may interfere with creatine transport in the gut. Although there
is some evidence that ingesting creatine with large amounts of glucose or glucose/protein optimizes creatine storage,
little is known whether any other types of products promote creatine retention. Therefore, the purpose of this pilot
study was to examine the effects of ingesting several nutritional strategies designed to enhance creatine uptake on
whole body creatine retention.
METHODS
Subjects
Sixteen apparently healthy males with no history of creatine use participated in this pilot study. All subjects in this
investigation participated in a familiarization session. During the familiarization session, subjects were informed as to
the experimental procedures, completed a personal/medical history form, exercise history form, creatine
supplementation history form, and signed informed consent statements in adherence with the human subject’s
guidelines of Arkansas State University and the American College of Sports Medicine. Subject’s descriptive
characteristics were (mean ±SD) 22.3±1.4 yrs, 82±8 kg, and 182±6 cm. No subject in this trial was a vegetarian and
all subjects reportedly consumed daily diets inclusive of meat.
Supplementation Protocol
Subjects donated a 24-hr urine sample on the day preceding the initiation of supplementation in order to establish
the subject’s normal daily excretion of creatine in response to their normal diet. After this control day, subjects
were matched according to total body mass and randomly assigned to ingest in a single-blind manner one of the
following supplements four times daily for 3-d.
Placebo (P): 5 g of dextrose with one 0.5 g capsule of corn starch.
Creatine Monohydrate (CM): 5 g of CM with one 0.5 g capsule of corn starch.
Creatine Monohydrate + Dextrose (CM + D): 5 g of CM + 18 g dextrose;
Effervescent Creatine (EC) 5 g of creatine citrate + 18 g dextrose + 320 mg of sodium [as sodium
carbonate and bicarbonate] + 175 mg of potassium [as potassium bicarbonate])
Subjects were instructed to mix the powdered supplements with water and to ingest the supplements at 8:00 a.m.,
12:00 p.m., 4.00 p.m., and 8.00 p.m. each day in order to standardize supplement intake. Dextrose and creatine
powders were placed in generic single serving packets for single-blind administration and were comprised of similar
mesh size, texture, taste, and appearance. The creatine monohydrate used in the study was from SKW (Trotsberg,
Germany) and the effervescent creatine was obtained from FSI Nutrition (Boys Town, Nebraska). Subject
Creatine Retention Following 3 Formulations of Creatine Ingestion
39
compliance in taking the supplements was verified daily by research assistants and all subjects were instructed to
maintain their regular eating habits during the investigation period. Subjects’ dietary intake was monitored with daily
nutritional logs that were turned in each morning and it was noted that all subjects were meat eaters.
Procedures
During the familiar session, subjects were instructed by the primary investigator on how to record nutritional intake
on the provided nutritional log sheets. In addition, the primary investigator disseminated in a single blind manner the
respective creatine products along with a verbal and written description of the supplementation protocol. Subjects
were provided eight 3 L urine collection containers in order to collect 24 hr urine samples over the course of the
study and were also requested to record the number of times they urinated each day. The 24 hr baseline urine sample
time parameter was initiated at 8 am the day before supplementation protocols began. Subjects were asked to
refrigerate their urine samples during the 24 hr time period.
Subjects reported daily to the Human Performance Laboratory between 7 and 8 am in order to drop off urine
samples. Subjects also turned in daily nutritional intake logs, which included type and amount of fluid ingested over
the 24 hr time period. Urine volume and fluid intake for the 24 hr period were recorded. Urine samples were
vortexed and a standard qualitative urinalysis was performed to assess urine specific gravity (Chem Strip 10SG,
Roche Diagnostics, Indianapolis, IN). In addition, approximately 10 ml of urine was transferred into labeled urine
storage tubes and stored at -80 C°. Urine samples were shipped on dry ice to researchers in the Department of
Biomedical Sciences, Queen’s Medical Center, at the University of Nottingham, England for blinded analysis of
creatine and creatinine levels using standard high performance liquid chromatography (HPLC) methods (2,3,5).
Daily creatine and creatinine excretion (g) were determined by multiplying daily excretion (g/L) by urine volume
expressed in L. Daily creatine retention was calculated by subtracting daily creatine excretion (g) from daily
supplemental creatine (20 g). Cumulative creatine retention was determined by subtracting the total amount of
creatine excreted over the 3-d supplementation period from the total amount of creatine supplemented to the diet
during the 3-day loading period (i.e., 60 g). Percent creatine retention was determined by dividing the cumulative
amount of creatine retained over the supplementation period by the total amount of creatine supplemented to the diet.
Statistical Analyses
Data were analyzed by repeated measure ANOVA with LSD post-hoc procedures for all daily measurements. A
factorial ANOVA with LSD post-hoc procedure was used to assess all cumulative (i.e., 3 day) data measures. Data
were analyzed using the SPSS for Windows version 10.05 statistical package (SPSS Inc., Chicago, IL). Statistical
significance was determined as p<0.05. Data are presented as means±SD.
RESULTS
No significant interactions (p>0.05) were observed among groups in fluid intake, urine specific gravity, or urinary
creatinine excretion. Table 1 presents mean daily urine volume, creatine excretion, and creatine retention observed
for the placebo (P), creatine monohydrate (CM), creatine monohydrate dextrose (C+D), and effervescent creatine
(EC) groups. No significant interactions were observed among groups in urine volume. Daily creatine excretion
expressed in g/L increased in all groups ingesting creatine during the supplementation period in comparison to their
control day and the placebo group. Significant differences were also observed among the creatine supplementation
treatments. Post-hoc analysis revealed that creatine excretion was greater in the CM and EC groups in comparison to
the C + D group. Significant group effects (p=0.001) were also observed among daily estimated creatine retentions
during the 3-d creatine-loading period. Average daily creatine retention was 0±0, 12.2±1.3, 16.1±2.2, and 12.6±2.5,
g/d for the P, CM, C+D, and HP groups respectively. Post-hoc analysis revealed that average daily creatine retention
was significantly greater in the C+D group in comparison to the P, CM, and EC groups. This resulted in a greater
percentage of creatine retention in the CD group (D=0±0; CM=61±15; C+D=80±11; EC=63±13 %, p=0.001).
Creatine Retention Following 3 Formulations of Creatine Ingestion
40
0
10
20
30
40
50
60
Placebo Creatine Monohydrate Creatine + Dextrose Effervescent Creatine
Grams
c
d
e
b
d
b
c
e
b
d
Figure 1. Three-
day cumulative creatine retention for the placebo (P),
creatine monohydrate (CM), creatine + dextrose (C + D), and
effervescent creatine (EC) groups. Data are means±±SD. a=p<0.05
from placebo. b=p<0.05 from CM. c=p<0.05 from C + D. d=p<0.05
from EC.
Table 1. Daily urine volume, urinary creatine excretion, and estimated
creatine retention observed for the placebo (P), creatine monohydrate
(CM), creatine + dextrose (C+D), and effervescent creatine (EC) groups.
Control Day 1 Day 2 Day 3
Urine Volume (L) P
1.50±0.54 2.12±0.47 1.74±0.50 1.63±0.45
CM
2.16±0.70 3.10±1.10 2.66±1.32 3.31±1.13
C+D
2.50±0.42 2.13±0.40 2.00±0.40 2.00±0.52
EC
1.73±0.60 2.70±1.14 3.00±1.50 2.70±1.70
Urine Creatine (g/L) P
0.14±0.08 0.16±0.05 ce 0.12±0.05 ce 0.12±0.06 ce
CM
0.54± 0.64
5.54±2.55 abd 8.58±3.78 abd 9.28±6.3 ab
C+D
0.30±0.27 2.60±1.54 ace 3.00 ±1.40ace 6.42±3.72 a
EC
0.28±1.70 7.30±2.10abd 8.01±3.00 abd 7.00±6.42 ab
Creatine Retention (g/d)
P
0±0 bced 0±0 bced 0±0 bced
CM
14.46±2.55 bd
11.41±3.76 bd 10.72±6.30 b
C+D
17.40±1.54 bce
17.01±1.40 bce 13.603.72± b
EC
12.72±2.07 bd
11.42± 3.80 bd
10.72±6.30 b
a = p<0.05 difference from control day; b = p<0.05 from the P group.
c = p<0.05 from the CM group; d = p<0.05 from the C + D group.
e = p<0.05 from the EC group
Figure 1 presents the estimated cumulative
creatine retention expressed in grams observed
during the 3 day loading period. ANOVA
revealed significant differences among groups
(p=0.001) in total creatine retention. Post-hoc
analysis indicated that creatine supplementation
increased whole body creatine retention in all
groups in comparison to P group. However,
creatine retention in the C+D group was
significantly greater (p<0.001) than the CM
group while no differences were observed
between the EC and CM groups. Figure 2
presents the estimated cumulative percentage
of supplemental creatine retained during the 3-
d loading period for the P, CM, C+D, EC
groups, respectively. Further, significant
differences (p=0.001) were similarly observed
among groups when creatine retention was
expressed as a percentage of total creatine
supplemented in the diet.
DISCUSSION
The major finding from this study is that creatine retention in the C (5g)+D (18 g) group was significantly greater
than the CM group and that EC+D supplementation did not promote greater creatine retention compared to CM
supplementation. These findings are important because until now the only known methods for enhancing creatine
Creatine Retention Following 3 Formulations of Creatine Ingestion
41
0
10
20
30
40
50
60
70
80
90
Placebo Creatine Monohydrate Creatine + Dextrose Effervescent Creatine
Percent %
c
d
e
b
d
b
c
e
Figure 2. Percentage of creatine retained during the 3 day loading
period for the placebo (P), creatine monohydrate (CM), creatine +
dextrose(C + D) and effervescent creatine (EC) groups. Data are
means±±SD. a=p<0.05 from placebo.
b=p<0.05 from CM. c=p<0.05
from C + D. d=p<0.05 from EC.
uptake have been by co-ingestion of creatine
with large amounts of glucose (e.g., 35-97 g)
and/or glucose and protein (~50 g each) (2-5) or
by ingesting low dosages of D-Pinitol (7).
Harris and coworkers (1) were among the first
to show that the oral creatine monohydrate
supplementation (e.g., 5 g, 4-6 times per day, for
2 or more days) significantly increased total
creatine content of the quadriceps femoris
muscle. It was further observed that the greatest
uptake by skeletal muscle occurred in subjects
with a low initial total creatine content (1).
Several years later, Green and colleagues (2,3)
demonstrated via analysis of muscle biopsy,
urine, and plasma samples that ingesting 5 g of
creatine monohydrate, followed 30-minutes later
by ingesting 93 g of simple carbohydrate in
solution four times each day for 5 days resulted
in an increase in muscle phosphocreatine,
creatine, and total creatine compared to creatine
ingestion alone. These researchers also found that creatine plus carbohydrate ingestion dramatically elevated insulin
concentrations and glycogen synthesis. These findings led to the premise that creatine accumulation during creatine
supplementation in humans appears to be mediated in part by insulin. Investigation into this phenomenon has shown
that ingesting 35 g of carbohydrate with each dose of creatine may promote greater training adaptations than
ingesting creatine alone (4) and that the combination of carbohydrate (47g, 50g, 97g) and protein (50g) will also
augment creatine retention (5). Though this phenomenon is interesting, it can be onerous to the athlete, as one
would have to consume an extra 560 - 1,500 Kcals with creatine in order to promote these adaptations.
In a companion study to the present investigation, we evaluated whether D-pinitol supplementation during creatine
loading would affect whole body creatine retention in male subjects (7). Since D-pinitol has been reported to possess
insulin-like properties (8,9) and stimulate glucose uptake (10,11) it was theorized that the combination of creatine
monohydrate and D-pinitol might increase creatine retention. We found that co-administration of creatine
monohydrate (5g) with low-doses of D-pinitol (0.5g, twice/day) offered a non-caloric means of augmenting whole
body creatine stores. However, since D-pinitol is fairly expensive, it has yet to be heavily marketed for consumer use
in relation to augmenting creatine retention. Consequently, there has been interest in determining whether other
nutritional interventions may augment creatine retention such as the present study suggesting lower dosages (18 g) of
carbohydrate supplementation that are more affordable.
Another interesting finding in this study was that effervescent creatine supplementation did not promote greater
whole body creatine retention compared to creatine monohydrate supplementation alone. The primary difference
between these two strategies is that effervescent creatine provides creatine citrate rather than creatine monohydrate in
a carbohydrate containing effervescent drink theoretically designed to optimize creatine delivery to the muscle. This
finding contrasts marketed claims that effervescent creatine is a better means of promoting whole body creatine
retention than creatine monohydrate. Further, that improving the mixing characteristics of creatine in fluid through
adding effervescence; optimizing the pH of the fluid creatine is mixed to prevent degradation to creatinine; and/or
attempting to minimize GI distress affects whole body creatine retention. Although one study has reported ergogenic
benefit from effervescent creatine citrate supplementation (12), we know of no other investigations that have
Creatine Retention Following 3 Formulations of Creatine Ingestion
42
examined the efficacy of effervescent creatine citrate on whole body creatine retention. However, present findings
suggest that effervescent creatine may actually be a less efficient means of augmenting whole body creatine stores. In
this regard, the present study revealed that adding 18 g of dextrose to creatine monohydrate promoted greater whole
body creatine retention than ingesting creatine monohydrate alone or effervescent creatine. Since the effervescent
creatine also contained 18 g of dextrose, one would expect that effervescent creatine would at least promote a similar
increase in whole body creatine retention than the creatine + dextrose group. Since the effervescent creatine group
promoted similar whole body creatine retention than creatine monohydrate alone, it could be argued that creatine
citrate is a less efficient form of creatine than creatine monohydrate. Speculatively, this reduced absorption efficiency
may be due to variations in intestinal and/or muscle absorption characteristics of creatine citrate in comparison to
creatine monohydrate. However, more research is needed to examine possible differences between creatine citrate
and creatine monohydrate before conclusions can be drawn.
In summary, results of this pilot study indicate that ingesting dextrose (18 g) with CM (5 g) significantly augments
whole body creatine retention over a three-day period. This finding is important because to date, previous
investigations have utilized larger quantities of carbohydrate (35-97g) to enhance creatine retention. Therefore, based
on the findings of this investigation, creatine retention can be increased even with relatively small amounts of
simultaneous carbohydrate ingestion. Further, effervescent creatine has been marketed as a highly effective method to
enhance creatine uptake but the results of this pilot study indicate that creatine citrate (EC) supplementation is no
more effective than ingesting CM alone. While the results of this study support previous research, additional research
is warranted to examine the possible influence that varying dosages of creatine monohydrate and dextrose
supplementation may have on levels of whole body creatine retention. Further, it is vital to continue the line of
research regarding the safety and efficacy of the several different forms of creatine that are being marketed today
(liquid, candy, gum, effervescent, creatine citrate, etc).
ACKNOWLEDGMENTS
We would like to thank the subjects who participated in this study and the laboratory assistants in the Human
Performance Laboratory at Arkansas State University who assisted in data acquisition and analysis. This study was
funded in part by MetaResponse Sciences (Laguna Niguel, CA). Investigators from Arkansas State collected,
analyzed and interpreted data from this study and have no financial interest in the outcome of results reported.
Presentation of results in this study does not constitute endorsement by the researchers or the institutions that they
are affiliated of the nutrients investigated.
Current address for M. Greenwood, PhD, CSCS*D, R.B. Kreider, PhD, EPC and C. Rasmussen, MS, CSCS, EPC is
The Exercise & Sport Nutrition Laboratory, Department of Health, Human Performance & Recreation Center for
Exercise, Nutrition, Preventive Health, Research, Baylor University, P.O. Box 97313 Waco, TX 76798-7313.
Current address for C. P. Earnest, PhD is The Cooper Institute, Division of Epidemiology & Clinical Applications,
12330 Preston Road, Dallas TX 75230. Current address for A.L. Almada, MSc is MetaResponse Sciences, Inc.,
30131 Town Center Drive, # 211, Laguna Niguel, CA 92677. Address correspondence to: Mike Greenwood, PhD,
CSCS*D.
Address for Correspondence: Michael Greenwood, PhD, CSCS *D, Exercise & Sport Nutrition Laboratory,
Department of HHPR, Baylor University, PO Box 97313, Waco, TX 76798-7313. Phone: (254) 710-7687;
FAX: (254) 710-3527 ; E-mail: Mike_Greenwood@baylor.edu
Creatine Retention Following 3 Formulations of Creatine Ingestion
43
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... In creatine research, the efficacy of creatine supplementation is determined by assessing the magnitude in which creatine supplementation protocol increases muscle creatine content as typically measured from muscle biopsy samples and/or muscle and brain creatine content as determined from magnetic resonance spectroscopy (MRS) [15]. Since oral ingestion of CrM is nearly 100% bioavailable (i.e., it's either absorbed by tissue or excreted in urine), whole-body creatine retention with CrM supplementation can also be estimated as the difference between daily intake of CrM and urinary creatine output [22]. Purported forms of creatine that do not increase blood creatine concentrations, do not increase uptake of creatine through tissue-specific creatine transporters, and ultimately do not increase tissue creatine levels by physiologically meaningful amounts would not affect creatine-related metabolic function. ...
... This is the reason that some researchers initially administered CrM to participants in warm to hot water [12] or hot tea [60]. Creatine solubility can also be improved by administering CrM in lower pH solutions like juices and sport drinks that generally have pH levels ranging from 2.5-3.5 [61] and/or blending CrM with carbohydrate and/or protein powders or in juice which helps suspend CrM in solution, reduce sedimentation, and enhance creatine uptake into muscle [20][21][22][23]62]. ...
... Prior studies indicate that CrM loading (i.e., 4 × 5 g/day for 5-7 days) or low-dose longterm intake (e.g., 3-6 g/day for 4-12 weeks) increases muscle creatine retention typically by 20-40% depending on initial creatine content in the muscle [12,22,[68][69][70][71]] and brain creatine content by 5-15% [72][73][74][75][76][77]. CrM supplementation has been reported to improve acute exercise performance particularly in intermittent high-intensity exercise bouts as well as enhance training adaptations in adolescents [78][79][80][81][82], young adults [29,55,[83][84][85][86][87][88][89][90][91][92], and older individuals [8,77,[93][94][95][96][97][98][99][100][101]. ...
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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.
... For most of these forms of creatine, reports show that they are no better than traditional creatine monohydrate in terms of strength gain or results achieved. [4] Reliable studies have yet to publish reports for creatine ethyl ester and creatine with cinnulin extract. However, recent research does suggest that adding it to β-alanine creatine monohydrate can produce greater effects than when taken creatine monohydrate alone. ...
... Additional studies have shown that creatine retention is increased by addition of dextrose or small amounts of Dpinitol (a herbal extract with insulin-like properties). While these nutritional supplements have proven to increase creatine retention in muscles, several recent studies show that these combinations are no more effective than creatine monohydrate to increase muscle strength and endurance or improve athletic performance [4]. Some other recent studies, however, point to potential positive effects on anaerobic strength, muscle hypertrophy, and muscle strength when combined with creatine protein [7]. ...
Article
The subject of the research is impact of creatine monohydrate on a mass of swimmers. The test was performed on a sample of 60 swimmers among members of the Academic Swimming Club „22. April“ divided into two groups aged between 21 and 25. All respondents are male and in good health. The respondents belonging to this population are at the zenith of morphological and motor development and are well motivated to advance in swimming. The measurement was carried out at the end of May and half of June 2008 at the premises of the Recreation Center Srpske Toplice (water temperature 28°C). The respondents were measured for body mass at baseline and after 21 days of taking creatine. The main objective of the paper is to determine whether taking creatine for three weeks shows significant differences in a mass gain of swimmers. The results of the research show that the differences in body mass between the two measurements have statistical significance.
... Consequently, creatine supplementation may help athletes recover from intense exercise and/or tolerate intensified periods of training to a greater degree. Third, there is evidence that athletes who supplement with creatine during training experience fewer musculoskeletal injuries, accelerated recovery time from injury [78,128] and less muscle atrophy after immobilization [129,130]. Whether this is due to a greater resistance to injury and/ or ability to recover from injury remains unclear. ...
... A number of different forms of creatine (e.g., creatine salts, creatine complexed with other nutrients, creatine dipeptides, etc.) have been marketed as more effective sources of creatine than creatine monohydrate [187]. However, there are no peer-reviewed published papers showing that the ingestion of equal amounts of creatine salts [188][189][190][191] or other forms of creatine like effervescent creatine [128], creatine ethyl ester [43,192,193], buffered creatine [41], creatine nitrate [194,195], creatine dipeptides, or the micro amounts of creatine contained in creatine serum [196] and beverages (e.g., 25-50 mg) increases creatine storage in muscle to a greater degree than creatine monohydrate [187]. In fact, most studies show that ingestion of these other forms have less physiological impact than creatine monohydrate on intramuscular creatine stores and/or performance and that any performance differences were more related to other nutrients that creatine is bound to or co-ingested with in supplement formulations. ...
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Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine ‘loading-phase’ required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.
... Steenge et al. (2000) compared a mixture of protein (50 g) and carbohydrates (47 g) co-ingested with creatine and found a significantly greater uptake compared to creatine alone. Greenwood et al. (2003) used a lower dose of carbohydrate (18 g) with creatine (5 g) and reported similar findings, that is, creatine uptake was significantly greater following co-ingestion compared to creatine alone. Similarly, Pittas et al. (2010) found that a lower-dose of protein mixed with carbohydrates (14 g protein hydrolysate, 7 g leucine, 7 g phenylalanine, and 57 g dextrose) co-ingested with creatine (5 g) augmented whole-body creatine retention over a 24 h period compared to a higher dose of carbohydrate (95 g) ingested with creatine, however, the uptake into skeletal muscle was not determined. ...
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It is well-established that creatine supplementation augments the gains in muscle mass and performance during periods of resistance training. However, whether the timing of creatine ingestion influences these physical and physiological adaptations is unclear. Muscle contractions increase blood flow and possibly creatine transport kinetics which has led some to speculate that creatine in close proximity to resistance training sessions may lead to superior improvements in muscle mass and performance. Furthermore, creatine co-ingested with carbohydrates or a mixture of carbohydrates and protein that alter insulin enhance creatine uptake. The purpose of this narrative review is to (i) discuss the purported mechanisms and variables that possibly justify creatine timing strategies, (ii) to critically evaluate research examining the strategic ingestion of creatine during a resistance training program, and (iii) provide future research directions pertaining to creatine timing.
... Similarly, Steenge et al., (2000) proposed that adding 47 g of carbohydrate and 50 g of protein to CM was as effective as adding 96 g of carbohydrate in boosting creatine levels [83] . Another study speculated that adding dextrose to the mix increased creatine levels [84] . Overall, it appears that the best results come from combining creatine monohydrate with carbohydrates or creatine with carbohydrates and proteins [49,85,86] . ...
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Athletes take nutritional supplements because they believe it will provide them with a convenient and effective source of nutrients. Creatine and ß-hydroxy-ß-methyl-butyrate (HMB) are two of the most popular and legal ergogenic dietary supplements. These two compounds may have a comparable ergogenic effect since they favor muscle protein synthesis and proteolysis during exercise. This narrative review seeks to offer the most recent scientific literature on these two ergogenic aids in detail. HMB has been found to improve strength and lean muscle mass by acting as an anti-catabolic agent, reducing muscle breakdown and protein degradation following exercise. In terms of muscle absorption and the ability to boost high-intensity exercise capacity, creatine monohydrate (CM) is the most clinically effective nutritional supplement. Athletes utilize creatine pills to boost their exercise performance. The combination of CM and HMB has the potential to increase fat-free mass while lowering fat mass.
... Another reason cited by the authors is the exercise protocol, as the 800-m run might be too short of using creatine as an ergogenic resource. It has also been reported that creatine intake is concomitant with carbohydrates or carbohydrates and proteins, which promotes consistent creatine absorption (Green et al., 1996;Greenwood et al., 2003;Steenge et al., 2000;Thomas et al., 2016). Moreover, the interval between creatine supplementation and placebo was 28 days (4 weeks), and previous research has shown that creatine reserves can take 4-6 weeks to return to baseline (Greenhaff, 1995;Hultman et al., 1996;Vandenberghe et al., 1997), depending on the athlete. ...
Article
This systematic review aimed to identify nutritional interventions and supplements that improve the performance for wheelchair athletes. Intervention trials involving high-performance wheelchair athletes were analyzed, including those that comprised a nutritional intervention, defined as any intervention related to food, beverages, and supplementation aiming at evaluating the performance of wheelchair athletes. Of the included studies, four evaluated caffeine supplementation, of which one also evaluated sodium citrate supplementation; two studies evaluated vitamin D supplementation; one study assessed creatine monohydrate supplementation; and one assessed carbohydrate supplementation. Most studies were conducted on athletes with spinal cord injury. Athletes who consumed caffeine exhibited an improvement in performance, but this finding is not strong enough to become a recommendation.
... Greater increases in muscle Cr are shown in those with lower initial muscle Cr content [5], while carbohydrate co-supplementation may increase Cr uptake via insulin-mediated stimulation [6,18] of the Cr transporter, CreaT. Although this mechanism of insulin stimulated Cr uptake remains to be mechanistically confirmed, if it holds true, this will only be relevant within the first few days at high doses (e.g., days 1 to 3 at 20 g·day −1 ) of supplementation prior to saturation of muscle Cr stores [19], but may be more relevant at lower doses (e.g., 3-5 g·day −1 , which takes up to 28 days to saturate). Indeed, the upper threshold of saturation across individuals appears remarkably consistent [1], meaning the dosing protocol will be important. ...
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Creatine has been considered an effective ergogenic aid for several decades; it can help athletes engaged in a variety of sports and obtain performance gains. Creatine supplementation increases muscle creatine stores; several factors have been identified that may modify the intramuscular increase and subsequent performance benefits, including baseline muscle Cr content, type II muscle fibre content and size, habitual dietary intake of Cr, aging, and exercise. Timing of creatine supplementation in relation to exercise has recently been proposed as an important consideration to optimise muscle loading and performance gains, although current consensus is lacking regarding the ideal ingestion time. Research has shifted towards comparing creatine supplementation strategies pre-, during-, or post-exercise. Emerging evidence suggests greater benefits when creatine is consumed after exercise compared to pre-exercise, although methodological limitations currently preclude solid conclusions. Furthermore, physiological and mechanistic data are lacking, in regard to claims that the timing of creatine supplementation around exercise moderates gains in muscle creatine and exercise performance. This review discusses novel scientific evidence on the timing of creatine intake, the possible mechanisms that may be involved, and whether the timing of creatine supplementation around exercise is truly a real concern.
... Although several other forms of creatine have been proposed and marketed as alternatives, none have been shown to offer benefits above and beyond those seen with monohydrate. In this respect, a number of studies have been completed comparing various alternative forms of creatine, and the interested reader is directed to the following papers: [3][4][5]30,[159][160][161][162][163]. In this respect, one must also realize that several studies have sought to examine the impact of combining creatine with other ingredients, such as beta-alanine [164,165], beta-hydroxy-beta-methylbutyrate (HMB) [96,[166][167][168][169][170][171], glutamine [72], sodium bicarbonate [47], carbohydrates [22,44,99,172,173], and protein [22,59,99] to examine the potential for any synergistic outcomes. ...
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Creatine is one of the most studied and popular ergogenic aids for athletes and recreational weightlifters seeking to improve sport and exercise performance, augment exercise training adaptations, and mitigate recovery time. Studies consistently reveal that creatine supplementation exerts positive ergogenic effects on single and multiple bouts of short-duration, high-intensity exercise activities, in addition to potentiating exercise training adaptations. In this respect, supplementation consistently demonstrates the ability to enlarge the pool of intracellular creatine, leading to an amplification of the cell’s ability to resynthesize adenosine triphosphate. This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass. Additionally, creatine supplementation may speed up recovery time between bouts of intense exercise by mitigating muscle damage and promoting the faster recovery of lost force-production potential. Conversely, contradictory findings exist in the literature regarding the potential ergogenic benefits of creatine during intermittent and continuous endurance-type exercise, as well as in those athletic tasks where an increase in body mass may hinder enhanced performance. The purpose of this review was to summarize the existing literature surrounding the efficacy of creatine supplementation on exercise and sports performance, along with recovery factors in healthy populations.
... By contrast, other studies comparing serum Cr levels after ingestion of CrM and Cr nitrate or CEE have reported significantly higher serum Cr concentrations after CrM ingestion (13,35). In a study by Greenwood et al. investigating whole-body Cr retention, TCC in an effervescent form did not enhance whole-body Cr retention more than CrM (16). In this review, the above results were not determined to be substantial on exercise outcomes because it is ultimately the total change in intramuscular Cr stores, not plasma Cr levels, that provides ergogenic benefit (6,15,17,32). ...
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Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion’s survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.
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The purpose of this study was to examine the changes in bench press strength (BPS), vertical jump (VJ), 100 yd dash time, and fat-free weight (FFW) in football players following 8 weeks of supplementation with a carbohydrate placebo (CHO), creatine monohydrate (CM), or CM plus CHO. Using a double blind random design, 24 college football players were placed into one of three treatment conditions: CHO) 35g CHO; CM) 5.25g CM plus 1g CHO; or CM+CHO) 5.25g CM and 33g CHO. All treatments were similar in taste and were ingested four times per day for five consecutive days and twice daily thereafter. All subjects weight trained for 1 h and participated in 30 min of speed drills four times per week for 8 weeks. The CM+CHO group experienced significant (p<0.05) improvement in BPS, VJ, 100 yd dash time and FFW when compared to the CHO group. However, delta scores for the CM group were not significantly different from the CHO group. These data suggest that CHO taken with CM during training may be superior to training alone for enhancing exercise performance and FFW.
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The purpose of this investigation was to determine the effect of creatine (Cr) loading on the onset of neuromuscular fatigue by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at the fatigue threshold (PWC(FT)) test. Using a double-blind random design, 15 women athletes [mean age 19.0 +/- 2.0 (SD) yr] from the university crew team received a placebo (n = 8; 20 g glucose) or Cr (n = 7; 5 g Cr monohydrate + 20 g glucose) four times per day for 5 consecutive days. Analysis of covariance was used to analyze the data (covaried for presupplementation PWC(FT) values). The adjusted mean postsupplementation PWC(FT) value for the Cr group (mean = 186 W) was significantly (P < 0.05) higher than that of the placebo group (mean = 155 W). These findings suggest that Cr loading may delay the onset of neuromuscular fatigue.
Article
Isulin is shown to directly enhance both the rate of transport and the uptake of cretine in vitro in isolated rat skeletal muscle. This action of the hormone on creatine transport is similar to that reported for the transport of some amino acids and sugars.
Article
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.
Article
Blood and urine samples were obtained from four groups of healthy male subjects (A-D, total n = 22) before, during and after ingesting the following: group A, 5 g of creatine in solution; groups B and C, 5 g of creatine and 93 g of simple carbohydrate in solution: group D, a creatine- and carbohydrate-free solution. Subjects ingested the above preparations every 4 h for the remainder of the day and throughout the next day (total daily creatine dose = 20 g), and reported back to the laboratory on day 3 to undergo the same procedures as on day 1. Throughout this time, subjects weighed and recorded all dietary intake, and those in groups B and C ingested a prescribed isoenergetic high carbohydrate diet. Subjects in group C also performed 1 h of cycling exercise at 70% of their maximal oxygen consumption on the morning of each day. On both days 1 and 3, peak plasma creatine concentration, the area under the plasma creatine concentration/time curve and urinary creatine concentration were lower in groups B and C than in group A. Conversely, serum insulin concentration was higher in groups B and C than in A. No differences were evident when comparing groups B and C. These data suggest carbohydrate ingestion augmented creatine retention during creatine feeding and that creatine retention was not further increased when exercise was performed prior to ingestion.
Article
This study investigated the effect of carbohydrate (CHO) ingestion on skeletal muscle creatine (Cr) accumulation during Cr supplementation in humans. Muscle biopsy, urine, and plasma samples were obtained from 24 males before and after ingesting 5 g Cr in solution (group A) or 5 g Cr followed, 30 min later, by 93 g simple CHO in solution (group B) four times each day for 5 days. Supplementation resulted in an increase in muscle phosphocreatine (PCr), Cr, and total creatine (TCr; sum of PCr and Cr) concentration in groups A and B, but the increase in TCr in group B was 60% greater than in group A (P < 0.01). There was also a corresponding decrease in urinary Cr excretion in group B (P < 0.001). Creatine supplementation had no effect on serum insulin concentration, but Cr and CHO ingestion dramatically elevated insulin concentration (P < 0.001). These findings demonstrate that CHO ingestion substantially augments muscle Cr accumulation during Cr feeding in humans, which appears to be insulin mediated.
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During the past few years, the insulin signalling system has emerged as a flexible network of interacting proteins. By utilizing the insulin receptor substrate (IRS)-proteins (IRS-1 and IRS-2), the insulin signal can be amplified or attenuated independently of insulin binding and tyrosine kinase activity, providing an extensible mechanism for signal transmission in multiple cellular backgrounds. By employing IRS-proteins to engage various signalling proteins, the insulin receptor avoids the stoichiometric constraints encountered by receptors which directly recruit SH2-proteins to their autophosphorylation sites. Finally, the shared use of IRS-proteins by multiple receptors is likely to reveal important connections between insulin and other hormones and cytokines which were previously unrecognized, or observed but unexplained.
Article
D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study investigates the effect of D-pinitol on glucose homeostasis in animal models of diabetes, and on glucose transport by cultured muscle cells. Plasma glucose concentrations were measured in normal, obese-diabetic (ob/ob) and streptozotocin (STZ)-diabetic mice after oral (p.o.) and intraperitoneal (i.p.) administration of D-pinitol. Glucose transport was measured in L6 rat muscle cells by 2-deoxyglucose (2DG) uptake. In STZ-diabetic mice, 100 mg kg−1 p.o. D-pinitol acutely decreased the hyperglycaemia (by 22% at 6 h). A similar decrease in plasma glucose (by 21%) was observed after 100 mg kg−1 i.p. D-pinitol. Insulin concentrations and the rate of insulin-induced (1 unit kg−1 actrapid i.p.) glucose disappearance were not altered by 100 mg kg−1 p.o. D-pinitol. Chronic administration of D-pinitol (100 mg kg−1 i.p. twice daily for 11 days) to STZ-diabetic mice maintained a reduction in plasma glucose concentrations from about 14 to 10 mmol l−1. In normal non-diabetic and severely insulin resistant ob/ob mice, 100 mg kg−1 p.o. D-pinitol did not significantly affect plasma glucose or insulin during acute studies. Incubation of L6 muscle cells with D-pinitol (10−3 M) increased basal 2DG uptake by 41% after 10 min and by 34% after 4 h. The effect of D-pinitol was inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. D-pinitol did not increase insulin-stimulated 2DG uptake by L6 cells. The data support the view that D-pinitol can exert an insulin-like effect to improve glycaemic control in hypoinsulinaemic STZ-diabetic mice. D-pinitol may act via a post-receptor pathway of insulin action affecting glucose uptake. British Journal of Pharmacology (2000) 130, 1944–1948; doi:10.1038/sj.bjp.0703523