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Timing of Creatine Supplementation and Resistance Training: A Brief Review

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The combination of creatine monohydrate supplementation and resistance training increases muscle mass and strength. In this brief narrative review, we propose that the timing of creatine supplementation in relation to resistance training may be an important factor to optimize hypertrophy and strength gains. Meta-analyses indicated that creatine supplementation immediately after resistance training was superior for increasing muscle mass compared to creatine supplementation immediately before resistance training (3 studies, standard mean difference 0.52, 95% CI 0.03-1.00, p = 0.04); however, this did not translate into greater muscular strength (p > 0.05). Further research is needed to confirm these limited findings and to determine the mechanisms explaining the potential greater increase in muscle mass from post-exercise creatine.
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2018, Volume 1 (Issue 5) OPEN ACCESS
Journal(of(Exercise(and(Nutrition(
!
Timing of Creatine Supplementation
and Resistance Training: A Brief
Review
Short Review,
Scott C. Forbes1, Darren G. Candow2
1Department of Physical Education, Brandon University, Brandon, Manitoba, Canada
2Faculty of Kinesiology & Health Studies, University of Regina, Regina, Saskatchewan, Canada
Abstract
The combination of creatine monohydrate supplementation and
resistance training increases muscle mass and strength. In this
brief narrative review, we propose that the timing of creatine
supplementation in relation to resistance training may be an
important factor to optimize hypertrophy and strength gains.
Meta-analyses indicated that creatine supplementation
immediately after resistance training was superior for increasing
muscle mass compared to creatine supplementation immediately
before resistance training (3 studies, standard mean difference
0.52, 95% CI 0.03 1.00, p = 0.04); however, this did not translate
into greater muscular strength (p > 0.05). Further research is
needed to confirm these limited findings and to determine the
mechanisms explaining the potential greater increase in muscle
mass from post-exercise creatine.!!
!
Key Words
: Supplements, Strength, Hypertrophy.
Corresponding author: Darren G. Candow, Darren.Candow@uregina.ca
Introduction
It is well established that resistance training increases muscle mass and strength over
time, possibly by increasing activation of the mammalian target of rapamycin
(mTOR) muscle protein synthetic pathway 1, satellite cell activation and proliferation
2, anabolic hormone production 3, and decreasing catabolic cytokine activity 4. The
combination of creatine supplementation and resistance training leads to greater
gains in muscle mass and strength compared to resistance training or creatine alone5.
Recent evidence suggests that the timing of ingestion may be an important factor
contributing to the greater gains in muscle mass and strength from creatine
supplementation 6,7,8,9. Specifically, (1) creatine supplementation immediately before
and immediately after resistance training sessions increases upper-and lower-body
strength more than placebo and resistance training 7, (2) post-exercise creatine
increases muscle mass compared to placebo 7, (3) pre-exercise and post-exercise
creatine supplementation increases muscle mass and strength compared to
consuming creatine in the hours (> 5) leading up to and following resistance training
9, and (4) post-exercise creatine increases muscle mass (trend) compared to pre-
exercise creatine 6.
The purpose of this review is to briefly outline the potential beneficial effects of
creatine supplementation and to evaluate the emerging evidence suggesting that the
timing of creatine ingestion may be an important factor to consider when designing
2018, Volume 1 (Issue 5) OPEN ACCESS
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an effective creatine supplementation protocol. We performed meta-analyses to
assess the effect of creatine timing on muscle hypertrophy and strength.
Methods
We searched PubMed and SPORTDiscus databases using the key words “creatine
supplementation”, “timing”, and a variety of synonyms for “resistance training” (e.g.,
“strength training”) on August 21, 2018. Our inclusion criteria included i) a direct
evaluation of creatine timing ii) inclusion of a resistance training program, with
measures of lean tissue mass and/or strength, and iii) utilized a randomized, repeated
measures design. Mean changes and the standard deviation of mean changes were
extracted. If mean changes were not extractable, the authors were contacted to obtain
the raw data for calculations. The homogeneity of the effect size among studies was
assessed using a X2 test. Since the homogeneity was low, we used fixed effects models
to calculate the pooled mean net change of lean tissue mass and strength comparing
creatine supplementation provided before versus after resistance training. Mean
changes and standard deviations for mean changes for individual studies and the
pooled effects and their 95% confidence intervals were calculated and Forest plots
were generated using Review Manage 5.3 software. Meta-analyses for lean tissue mass
and maximum strength were only performed when 3 or more studies utilizing similar
interventions and outcomes were available. Significance was set at p 0.05.
Creatine Supplementation
Creatine or methyl-guanidino acetic acid, is a naturally occurring nitrogen-containing
compound found primarily in red meat and seafood 10. Creatine excretion typically
occurs at a rate of ~2 g·d-1 10. Creatine can be replaced via endogenous synthesis (1-
2 g·d-1) in the kidneys, liver, and pancreas or exogenously through dietary intake,
typically ~1-3 g·d-1 10,11. Ninety-five percent of creatine is stored in skeletal muscle,
of which 60-70% is phosphorylated (i.e. phosphocreatine; 12) and the remainder is
free creatine. Phosphocreatine rapidly re-synthesizes adenosine diphosphate (ADP)
to maintain adenosine triphosphate (ATP) during high intensity exercise 12. Elevated
phosphocreatine stores (via exogenous creatine) may increase exercise training
intensity and capacity leading to greater muscle accretion and strength over time
[reviewed in 13]. There are several purported mechanisms which may explain the
greater increase in muscle mass and strength observed from creatine
supplementation. Creatine supplementation elevates skeletal phosphocreatine and
total creatine stores 14, which increases phosphocreatine re-synthesis 15 and exercise
fatigue resistance 16. Creatine influences myocellular water retention due to increased
intracellular osmolarity and increases muscle glycogen storage 17. Muscle cell swelling
may stimulate genes (i.e., myosin heavy chain I and IIA) regulating various anabolic
signaling pathways 18. Furthermore, creatine increases satellite cell differentiation 19,
activity 20, and content 21; myogenic transcription factor activity 22, hormonal
secretions (e.g. IGF-1; 23), muscle protein kinetics 24, and decreases inflammation 25.
Creatine Timing
The timing of ingestion may be an important factor contributing to the greater gains
in muscle mass and strength from creatine supplementation (Table 1). Creatine
immediately before (~ 5 minutes) or immediately after (~ 5 minutes) resistance
training sessions for 8 months increased leg press strength (creatine before = 27%;
creatine after = 28%) and chest press strength (creatine before = 30%; creatine after
= 36%) compared to placebo (leg press: 4%; chest press: 4%; p < 0.05) in healthy
older adults 7. Interestingly, post-exercise creatine increased whole-body lean tissue
mass (6.4%) compared to placebo (1.2%; p<0.05), while there was no difference
between pre-exercise creatine and placebo 7. Furthermore, consuming creatine
immediately before (0.05 g·kg-1 of body weight) and immediately after (0.05 g·kg-1 of
body weight) resistance training sessions (3 days/week, 10 weeks) resulted in greater
muscle accretion (2.0 ± 0.3 cm) compared to placebo (0.8 ± 0.3 cm) in healthy older
males (59-77 years; 8). These results support previous findings of a significant
2018, Volume 1 (Issue 5) OPEN ACCESS
Journal(of(Exercise(and(Nutrition(
increase in lean tissue mass (6%), type II muscle fiber area (29%), and insulin growth-
factor I (78%) in adults (19-55 years) who ingested creatine before (0.03 g·kg-1 of
body weight) and after (0.03 g·kg-1 of body weight) resistance training for 8 weeks 23,
26. In addition, a creatine supplement (1 g·kg-1: supplement per 100 g = 40 g protein,
43 g glucose, 7 g creatine and <0.5 g fat) immediately before and immediately after
resistance training sessions for 10 weeks significantly increased intramuscular
creatine content, lean tissue mass, muscle cross sectional-area of type II fibers and
maximal strength in resistance trained body-builders compared to consuming
creatine > 5 hours before and after exercise (i.e., before breakfast and immediately
prior to sleep; 9).
In directly comparing pre-exercise creatine to post-exercise creatine, Antonio and
Ciccone 6 found a greater muscle benefit (i.e., fat-free mass and strength) from post-
exercise creatine (fat-free mass = 3% gain; 1 repetition maximum bench press =
7.5%) in young recreational male bodybuilders compared to pre-exercise creatine
supplementation (fat-free mass = 1.3% gain; 1 repetition maximum bench press =
6.8%). However, Candow et al. 7,8 found no statistical difference between pre-
exercise creatine and post-exercise creatine after either 12 weeks 8 or 8 months 7 of
resistance training in older adults. Results across studies suggest that pre-exercise and
post-exercise creatine supplementation has beneficial effects on muscle mass and
strength with slightly greater gains from post-exercise creatine.
Table 1. Studies investigation the effect of creatine ingestion before and after
resistance training.
FIRST
AUTHOR ,
YEAR
STUDY
POPULATION
INTERVENTION
DURATION
OUTCOME
MEASURES
ANTONIO
AND
CICCONE,
2013
N=19 Recreational Male
Bodybuilders; Age 23.1
± 2.9 yrs; Height: 166.0
± 23.2 cm; Weight: 80.18
± 10.43 kg
Randomly assigned:
CR (5g) PRE or CR
(5g) POST RT
sessions and anytime
on days off; 5 RT
sessions/wk
4 wks
FFM, FM, BM,
Bench Press 1RM
between groups;
Magnitude based
inference CR
POST possibly
more beneficial for
FFM, FM, 1RM BP
CANDOW
ET AL., 2014
N=22 (9 men; 13
women) non-RT healthy
older adults; Age 50-64
yrs
Randomly assigned:
CR before (n=11) (CR
0.1g/kg before +
0.1g/kg placebo after)
or CR after (n=11)
(0.1g/kg placebo
before + CR 0.1g/kg
after); RT 3d/wk
12 wks
FFM, limb
muscle thickness,
BP and LP 1RM
and no difference
in protein
catabolism (but all
these parameters
were improved by
RT). No changes in
Kidney function
over time.
CANDOW
ET AL., 2015
N= 39 (22 women, 17
men); non-RT healthy
older adults, Age 50-71
yrs
Randomly assigned:
CR before (CR
0.1g/kg before +
0.1g/kg placebo after)
or CR after (0.1g/kg
placebo before + CR
0.1g/kg after) or
Placebo control; RT
3d/wk
8 months
CR After LBM
compared to
Placebo. CR Before
LBM compared
to Placebo.
Between CR
groups for 1RM
bench press, 1RM
leg press, LBM. CR
groups strength
compared to
Placebo.
Abbreviations: CR = creatine; RT = resistance training; FFM = fat free mass; FM = Fat
mass; BM = body mass; RM = repetition maximum; BP = bench press; LP = leg press;
LBM = lean body mass
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Meta-Analysis Results
Mean changes and standard deviations for mean changes for individual studies and
pooled effects and their 95% confidence intervals are presented along with Forest
plots in Figures 1 and 2. When pooling the limited data, lean tissue mass (p = 0.04)
increased to a greater extent from post-exercise creatine compared to pre-exercise
creatine. These results provide preliminary evidence that creatine timing may be an
important factor to consider in designing a creatine supplementation protocol.
However, there were no differences between pre-exercise and post-exercise creatine
on maximal strength (Figure 2). It is important to note that only 3 trials were included
in the meta-analyses, which limits the statistical power to detect differences. Despite
this limitation, post-exercise creatine supplementation was statistically significant for
increasing lean tissue mass. However, additional research is needed to determine with
greater certainty whether post-exercise creatine is superior to pre-exercise creatine
for improving lean tissue mass.
Figure 1: Forest plot for absolute change in lean tissue mass. Comparing strategic
ingestion of creatine before versus after resistance training.
Figure 2: Forest plot for absolute change in 1 repetition maximum upper body
strength. Comparing strategic ingestion of creatine before versus after resistance
training.
Potential Mechanisms of Creatine Timing
The greater gains in muscle mass and strength observed from pre- and post-exercise
creatine may be due to an upregulation of the kinetics involved in creatine transport
27, by an increase in Na+-K+ pump function during exercise 27 and by an increase in
blood flow and delivery of creatine to exercising muscles 28. Tipton et al. 29 previously
showed that pre-exercise and post-exercise ingestion of an essential amino acid-
carbohydrate solution significantly increased net muscle protein synthesis in young
adults. The acute lower-body exercise session increased leg blood flow by 201-324%.
The authors concluded that providing amino acids at a time when blood flow is
elevated (i.e. during resistance training) maximizes delivery to muscle 29.
Conclusion
Based on the limited studies performed thus far, it appears that creatine
supplementation before and after resistance training sessions increases lean tissue
mass and strength. Our meta-analysis suggests that post-exercise creatine ingestion
provides greater muscle benefits than pre-exercise creatine. Further research is
warranted to confirm these findings and to elucidate the mechanisms explaining the
greater increase in muscle mass from post-exercise creatine.
Media-Friendly Summary
2018, Volume 1 (Issue 5) OPEN ACCESS
Journal(of(Exercise(and(Nutrition(
Creatine can enhance resistance training gains in muscle mass and strength. Presently,
there is limited data on when is the best time to take creatine in relation to training.
Based on the available evidence, it is recommended to take creatine after training to
maximize gains in muscle mass and strength; however, these findings are based on a
small sample size and precise mechanisms explaining these findings remain to be
determined.
Acknowledgements
The authors have no conflicts of interest.
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Creatine is a sports supplement with high scientific evidence on its effects on performance and with emerging health’s results, including for vegetarian athletes and older adults. The creatine type and effective doses have been well studied, presenting consistent results. However, not many studies have evaluated the ingestion timing in terms of its interaction with the creatine effects. The aim of this review is to analyze the different existing scientific literature on creatine supplementation protocols and their interaction with the timing of ingestion, in order to assess whether there is a greater effect of the ergogenic dose of creatine considered effective when It is ingested before, post workout or at another time of the day. The results of this work presented different types of protocols and doses in creatine supplementation, despite being diverse the protocols shown in the literature, the most effective consisted of a consumption of 0.3 g/kg/d for five days, followed by a consumption of 0.03 g/kg/d, thus achieving a greater reserve of PCr in skeletal muscle. Studies showed greater benefits when creatine intake was carried out in the moments close to workout due to greater blood flow, the studies pointing to significant improvements in post-workout consumption, since creatine can increase the rate of glycogen uptake in muscle and increase insulin sensitivity
... Creatine (N-aminoiminomethyl-N-methyl glycine) is a naturally occurring nitrogen containing compound found primarily in red meat, fish, and poultry [11][12][13] . Creatine has been shown to influence both muscle 10,14 and brain function 15 . The purpose of this brief review is to discuss the nuances of creatine supplementation for MMA athletes. ...
... Furthermore, it has been hypothesized that combining high doses of caffeine (> 5mg/kg) and creatine may be counterproductive due to competing mechanistic pathways 69 , however, from an applied perspective short term studies are inconsistent [69][70][71] and long term (> 4 weeks) co-ingestion studies are lacking. From a timing perspective, there appears to be a small advantage to ingesting creatine after exercise 14 . There have been three studies that have investigated the impact of creatine before compared to after and when included into a small meta-analysis, it appears to favor creatine after exercise for muscle hypertrophy but not for strength gains 14 . ...
... From a timing perspective, there appears to be a small advantage to ingesting creatine after exercise 14 . There have been three studies that have investigated the impact of creatine before compared to after and when included into a small meta-analysis, it appears to favor creatine after exercise for muscle hypertrophy but not for strength gains 14 . Importantly, no timing study has examined creatine uptake into the muscle and thus caution is warranted, and from a practical perspective the best time to take creatine (pending no or minimal gastrointestinal distress) is when the athlete will remember to take it. ...
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Mixed martial arts (MMA) is an intermittent sport that is physically and cognitively demanding. Nutritional strategies to support training, competition, and weight-cutting are important to optimize performance. One purported ergogenic aid that may have beneficial effects for MMA is creatine monohydrate. The purpose of this narrative review is to (1) discuss how creatine supplementation impacts MMA performance; (2) outline the effect of creatine supplementation on body composition and highlight specific strategies while cutting weight; (3) discuss how creatine can be used after weigh-ins to enhance re-hydration and glycogen re-synthesis; (4) evaluate the potential cognitive benefits of creatine supplementation; and (5) discuss practical real life strategies and considerations when considering creatine supplementation.
... A common theme across all studies was that creatine was consumed within 60 min' post-exercise. While the mechanistic actions of creatine were not determined in these studies, previous research has shown that prior muscle contractions (i.e., resistance training sessions) stimulate greater creatine uptake into muscle [50] possibly through increased activation of creatine transport kinetics [51,52]. These results may be important, as compliance to a creatine supplementation program may be higher when creatine is only consumed on training days. ...
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Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5–7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.
... On training days, participants mixed their supplement powder in water and consumed the solution 60 min prior to exercise. Sixty minutes was chosen because this is the approximate time it takes for peak plasma caffeine concentrations to occur after caffeine ingestion (Graham 2001) and pre-exercise creatine supplementation has a beneficial effect on muscle mass and performance (Forbes and Candow 2018). On nontraining days, participants were instructed to refrain from consuming their supplement as the purpose of the study was to investigate the effects of pre-exercise creatine and caffeine supplementation. ...
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The primary purpose was to determine the separate and combined effects of creatine and caffeine supplementation during resistance training on body composition and muscle performance in trained young adults. Twenty-eight participants were randomized to supplement with creatine and caffeine (CR-CAF; n = 9, 22 ± 4 years; 0.1 g·kg⁻¹·d⁻¹ of creatine monohydrate + 3 mg·kg⁻¹·d⁻¹ of caffeine anhydrous micronized powder); creatine (CR; n = 7, 22 ± 4 years, 0.1 g·kg⁻¹·d⁻¹ of creatine + 3 mg·kg⁻¹·d⁻¹ of micronized cellulose), caffeine (CAF; n = 6, 19 ± 1 years, 3 mg·kg⁻¹·d⁻¹ of caffeine + 0.1 g·kg⁻¹·d⁻¹ of maltodextrin) or placebo (PLA; n = 6, 23 ± 7 years, 0.1 g·kg⁻¹·d⁻¹ of maltodextrin + 3 mg·kg⁻¹·d⁻¹ micronized cellulose) one hour prior to performing resistance training for 6 weeks. Before and after training and supplementation, fat-free and fat mass (air-displacement plethysmography), muscle thickness (elbow and knee flexors and extensors; ultrasound), muscle strength (1-repetition maximum [1-RM] for the leg press and chest press), and endurance (one set of repetitions to volitional fatigue using 50% baseline 1-RM for leg press and chest press) were assessed. There was a group x time interaction (p = 0.049) for knee extensor muscle thickness with CR experiencing an increase over time with no changes in the other groups. There were no other between group differences for any variable. In conclusion, creatine supplementation and resistance training results in a small improvement in knee extensor muscle accretion in trained young adults.
... Harris et al. [7] showed that prior muscle contractions augmented total intramuscular creatine uptake from creatine supplementation, possibly through an upregulation in creatine transport kinetics, an increase in sodium-potassium pump function during exercise, or by an increase in blood flow delivery of creatine to exercising muscles (for review see [8]). Ingesting creatine immediately following each set of resistance training may therefore increase creatine uptake into skeletal muscle, which over time could lead to greater gains in muscle mass and performance compared to placebo. ...
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The purpose was to examine the effects of creatine supplementation during resistance training sessions on skeletal muscle mass and exercise performance in physically active young adults. Twenty-two participants were randomized to supplement with creatine (CR: n = 13, 26 ± 4 yrs; 0.0055 g·kg−1 post training set) or placebo (PLA: n = 9, 26 ± 5 yrs; 0.0055 g·kg−1 post training set) during six weeks of resistance training (18 sets per training session; five days per week). Prior to and following training and supplementation, measurements were made for muscle thickness (elbow and knee flexors/extensors, ankle plantarflexors), power (vertical jump and medicine ball throw), strength (leg press and chest press one-repetition maximum (1-RM)) and muscular endurance (one set of repetitions to volitional fatigue using 50% baseline 1-RM for leg press and chest press). The creatine group experienced a significant increase (p < 0.05) in leg press, chest press and total body strength and leg press endurance with no significant changes in the PLA group. Both groups improved total body endurance over time (p < 0.05), with greater gains observed in the creatine group. In conclusion, creatine ingestion during resistance training sessions is a viable strategy for improving muscle strength and some indices of muscle endurance in physically active young adults.
... A small meta-analysis involving 3 studies (n = 80, > 18 yrs, ranging from 4 to 32 weeks) showed that post-exercise creatine supplementation led to greater gains in muscle mass compared to preexercise creatine (standard mean difference 0.52, 95% CI 0.03 -1.00, p = 0.04; (84). There were no differences between pre-and post-exercise creatine for effects on muscle strength. ...
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Sarcopenia is an age-related muscle condition characterized by a reduction in muscle quantity, force generating capacity and physical performance. Sarcopenia occurs in 8–13% of adults ≥ 60 years of age and can lead to disability, frailty, and various other diseases. Over the past few decades, several leading research groups have focused their efforts on developing strategies and recommendations for attenuating sarcopenia. One potential nutritional intervention for sarcopenia is creatine supplementation. However, research is inconsistent regarding the effectiveness of creatine on aging muscle. The purpose of this perspective paper is to: (1) propose possible reasons for the inconsistent responsiveness to creatine in aging adults, (2) discuss the potential mechanistic actions of creatine on muscle biology, (3) determine whether the timing of creatine supplementation influences aging muscle, (4) evaluate the evidence investigating the effects of creatine with other compounds (protein, conjugated linoleic acid) in aging adults, and (5) provide insight regarding the safety of creatine for aging adults.
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BACKGROUND: Creatine supplementation has some beneficial effects on cognitive processing in healthy adults, including athletes; however the effects on cognitive function following exhaustive exercise in athletes is unknown. Therefore, the purpose was to determine the effects of 28 days of creatine supplementation on tasks of cognitive performance immediately following exhaustive exercise in Muay Thai female athletes compared to placebo. METHODS: Using a repeated measures, double-blind, placebo controlled design, 26 female Muay Thai athletes (age: 26 ± 5 years; body mass: 65.1 ± 6.6 kg; height: 162 ± 5 cm; training experience: 2.6 ± 0.6 years) were randomized to supplement with creatine monohydrate (3 g/day) or placebo (maltodextrin) for 28 days. Prior to and following supplementation, measures of cognitive performance were assessed (visual and auditory reaction time, corsi block test, visual forward digit span, and Erikson Flanker Task) immediately after exercise. RESULTS: There was a time main effect for auditory reaction time (p = 0.035), with no differences between groups. There was a trend for an interaction effect for visual reaction time (p = 0.067), visual go-no-go reaction time (p = 0.087), and Erikson Flanker task (p = 0.06), with exploratory post hoc tests revealing improvements over time in the creatine group (p < 0.05) with no changes in the PLA group (p > 0.05). CONCLUSION: Twenty-eight days of creatine supplementation appeared to have a small but positive effect on cognitive performance following exhaustive exercise in female Muay Thai athletes. Future research using a larger dose over a longer duration is warranted.
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Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).
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The purpose of this study was to compare changes in muscle insulin-like growth factor-I (IGF-I) content resulting from resistance-exercise training (RET) and creatine supplementation (CR). Male (n=24) and female (n=18) participants with minimal resistance-exercise-training experience (=1 year) who were participating in at least 30 min of structured physical activity (i.e., walking, jogging, cycling) 3-5 x/wk volunteered for the study. Participants were randomly assigned in blocks (gender) to supplement with creatine (CR: 0.25 g/kg lean-tissue mass for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body RET program for 8 wk. Eighteen participants were classified as vegetarian (lacto-ovo or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female). Muscle biopsies (vastus lateralis) were taken before and after the intervention and analyzed for IGF-I using standard immunohistochemical procedures. Stained muscle cross-sections were examined microscopically and IGF-I content quantified using image-analysis software. Results showed that RET increased intramuscular IGF-I content by 67%, with greater accumulation from CR (+78%) than PL (+54%; p=.06). There were no differences in IGF-I between vegetarians and nonvegetarians. These findings indicate that creatine supplementation during resistance-exercise training increases intramuscular IGF-I concentration in healthy men and women, independent of habitual dietary routine.
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We examined the effect of glycogen-depleting exercise on subsequent muscle total creatine (TCr) accumulation and glycogen resynthesis during postexercise periods when the diet was supplemented with carbohydrate (CHO) or creatine (Cr) + CHO. Fourteen subjects performed one-legged cycling exercise to exhaustion. Muscle biopsies were taken from the exhausted (Ex) and nonexhausted (Nex) limbs after exercise and after 6 h and 5 days of recovery, during which CHO (CHO group, n = 7) or Cr + CHO (Cr+CHO group, n = 7) supplements were ingested. Muscle TCr concentration ([TCr]) was unchanged in both groups 6 h after supplementation commenced but had increased in the Ex (P < 0.001) and Nex limbs (P < 0.05) of the Cr+CHO group after 5 days. Greater TCr accumulation was achieved in the Ex limbs (P < 0.01) of this group. Glycogen was increased above nonexercised concentrations in the Ex limbs of both groups after 5 days, with the concentration being greater in the Cr+CHO group (P = 0.06). Thus a single bout of exercise enhanced muscle Cr accumulation, and this effect was restricted to the exercised muscle. However, exercise also diminished CHO-mediated insulin release, which may have attenuated insulin-mediated muscle Cr accumulation. Ingesting Cr with CHO also augmented glycogen supercompensation in the exercised muscle.
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.
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Phosphocreatine (PCr) availability is likely to limit performance in brief, high-power exercise because the depletion of PCr results in an inability to maintain adenosine triphosphate (ATP) resynthesis at the rate required. It is now known that the daily ingestion of four 5-g doses of creatine for 5 days will significantly increase intramuscular creatine and PCr concentrations prior to exercise and will facilitate PCr resynthesis during recovery from exercise, particularly in those individuals with relatively low creatine concentrations prior to feeding. As a consequence of creatine ingestion, work output during repeated bouts of high-power exercise has been increased under a variety of experimental conditions. The reduced accumulation of ammonia and hypoxanthine in plasma and the attenuation of muscle ATP degradation after creatine feeding suggest that the ergogenic effect of creatine is achieved by better maintaining ATP turnover during contraction.
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Biopsy samples were obtained from the vastus lateralis muscle of eight subjects after 0, 20, 60, and 120 s of recovery from intense electrically evoked isometric contraction. Later (10 days), the same procedures were performed using the other leg, but subjects ingested 20 g creatine (Cr)/day for the preceding 5 days. Muscle ATP, phosphocreatine (PCr), free Cr, and lactate concentrations were measured, and total Cr was calculated as the sum of PCr and free Cr concentrations. In five of the eight subjects, Cr ingestion substantially increased muscle total Cr concentration (mean 29 +/- 3 mmol/kg dry matter, 25 +/- 3%; range 19-35 mmol/kg dry matter, 15-32%) and PCr resynthesis during recovery (mean 19 +/- 4 mmol/kg dry matter, 35 +/- 6%; range 11-28 mmol/kg dry matter, 23-53%). In the remaining three subjects, Cr ingestion had little effect on muscle total Cr concentration, producing increases of 8-9 mmol/kg dry matter (5-7%), and did not increase PCr resynthesis. The data suggest that a dietary-induced increase in muscle total Cr concentration can increase PCr resynthesis during the 2nd min of recovery from intense contraction.
Article
Limitations in energy supply is a classical hypothesis of muscle fatigue. The present paper reviews the evidence available from human studies that energy deficiency is an important factor in fatigue. The maximal rate of energy expenditure determined in skinned fibres is close to the rate of adenosine triphosphate (ATP) utilisation observed in vivo and data suggest that performance during short bursts of exercise (<5 s duration) primarily is limited by other factors than energy supply (e.g. Vmax of myosine adenosine triphosphatase (ATPase), motor unit recruitment, engaged muscle mass). Within 10 s of exercise maximal power output decreases considerably and coincides with depletion of phosphocreatine. During recovery, maximal force and power output is restored with a similar time course as the resynthesis of phosphocreatine. Increases in muscle store of phosphocreatine through dietary supplementation with creatine increases performance during high-intensity exercise. These findings support the hypothesis that energy supply limits performance during high-intensity exercise. It is well documented that pre-exercise muscle glycogen content is related to performance during moderate intensity exercise. Recent data indicates that the interfibre variation in phosphocreatine is large after prolonged exercise to fatigue and that some fibres are depleted to the same extent as after high-intensity exercise. Despite relatively small decreases in ATP, the products of ATP hydrolysis (Pi and free ADP) may increase considerably. Free ADP calculated from the creatine kinase reaction increases 10-fold both after high-intensity exercise and after prolonged exercise to fatigue. It is suggested that local increases in ADP may reach inhibitory levels for the contraction process.
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Nutritional status influences muscle growth and athletic performance, but little is known about the effect of nutritional supplements, such as creatine, on satellite cell mitotic activity. The purpose of this study was to examine the effect of oral creatine supplementation on muscle growth, compensatory hypertrophy, and satellite cell mitotic activity. Compensatory hypertrophy was induced in the rat plantaris muscle by removing the soleus and gastrocnemius muscles. Immediately following surgery, a group of six rats was provided with elevated levels of creatine monohydrate in their diet. Another group of six rats was maintained as a non-supplemented control group. Twelve days following surgery, all rats were implanted with mini-osmotic pumps containing the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label mitotically active satellite cells. Four weeks after the initial surgery the rats were killed, plantaris muscles were removed and weighed. Subsequently, BrdU-labeled and non-BrdU-labeled nuclei were identified on enzymatically isolated myofiber segments. Muscle mass and myofiber diameters were larger (P < 0.05) in the muscles that underwent compensatory hypertrophy compared to the control muscles, but there were no differences between muscles from creatine-supplemented and non-creatine-supplemented rats. Similarly, compensatory hypertrophy resulted in an increased (P < 0.05) number of BrdU-labeled myofiber nuclei, but creatine supplementation in combination with compensatory hypertrophy resulted in a higher (P < 0.05) number of BrdU-labeled myofiber nuclei compared to compensatory hypertrophy without creatine supplementation. Thus, creatine supplementation in combination with an increased functional load results in increased satellite cell mitotic activity.