Abstract
Background
Despite the robust evidence demonstrating positive effects from creatine supplementation (primarily when associated with resistance training) on measures of body composition, there is a lack of a comprehensive evaluation regarding the influence of creatine protocol parameters (including dose and form) on body mass and estimates of fat-free and fat mass.Methods
Randomized controlled trials (RCTs) evaluating the effect of creatine supplementation on body composition were included. Electronic databases, including PubMed, Web of Science, and Scopus were searched up to July 2023. Heterogeneity tests were performed. Random effect models were assessed based on the heterogeneity tests, and pooled data were examined to determine the weighted mean difference (WMD) with a 95% confidence interval (CI).Results
From 4831 initial records, a total of 143 studies met the inclusion criteria. Creatine supplementation increased body mass (WMD: 0.86 kg; 95% CI: 0.76 to 0.96, I2 = 0%) and fat-free mass (WMD: 0.82 kg; 95% CI: 0.57 to 1.06, I2 = 0%) while reducing body fat percentage (WMD: -0.28 %; 95% CI: -0.47 to -0.09; I2 = 0%). Studies that incorporated a maintenance dose of creatine or performed resistance training in conjunction with supplementation had greater effects on body composition.Conclusion
Creatine supplementation has a small effect on body mass and estimates of fat-free mass and body fat percentage. These findings were more robust when combined with resistance training.Free full text
Creatine supplementation protocols with or without training interventions on body composition: a GRADE-assessed systematic review and dose-response meta-analysis
ABSTRACT
Background
Despite the robust evidence demonstrating positive effects from creatine supplementation (primarily when associated with resistance training) on measures of body composition, there is a lack of a comprehensive evaluation regarding the influence of creatine protocol parameters (including dose and form) on body mass and estimates of fat-free and fat mass.
Methods
Randomized controlled trials (RCTs) evaluating the effect of creatine supplementation on body composition were included. Electronic databases, including PubMed, Web of Science, and Scopus were searched up to July 2023. Heterogeneity tests were performed. Random effect models were assessed based on the heterogeneity tests, and pooled data were examined to determine the weighted mean difference (WMD) with a 95% confidence interval (CI).
Results
From 4831 initial records, a total of 143 studies met the inclusion criteria. Creatine supplementation increased body mass (WMD: 0.86kg; 95% CI: 0.76 to 0.96, I2=0%) and fat-free mass (WMD: 0.82kg; 95% CI: 0.57 to 1.06, I2=0%) while reducing body fat percentage (WMD: −0.28 %; 95% CI: −0.47 to −0.09; I2=0%). Studies that incorporated a maintenance dose of creatine or performed resistance training in conjunction with supplementation had greater effects on body composition.
Conclusion
Creatine supplementation has a small effect on body mass and estimates of fat-free mass and body fat percentage. These findings were more robust when combined with resistance training.
1. Introduction
Creatine, a non-protein organic amino acid [1], is synthesized from arginine, glycine, and methionine [2]. Within a cell,~66% of creatine is stored as phosphocreatine (PCr) with the remainder stored as free creatine [2]. Creatine is degraded non-enzymatically into creatinine at a rate of 1–2% per day, which needs to be replaced via endogenous production and/or through exogenous sources (i.e. red meat, seafood, creatine supplementation). The combination of endogenous production (primarily in the liver and kidneys) and habitual dietary sources of creatine causes~80% intramuscular creatine saturation levels [3]. The addition of creatine supplementation further augments these levels by~20% [4]. Mechanistically, elevated stores of PCr will enhance the capacity to rapidly re-synthesize adenosine triphosphate (ATP). Furthermore, creatine is pleiotropic and can alter calcium, glycogen, protein kinetics, insulin-like growth factor-1, myogenic regulatory factors, satellite cells, inflammation, and oxidative stress [5].
The most common creatine supplementation protocols use either absolute or relative dosing strategies. From an absolute perspective, one strategy is to ingest 20g/day for 5–7 (referred to as the creatine loading phase) followed by 2–5g/day thereafter (creatine maintenance phase) [6]. This strategy is well established to increase intramuscular creatine stores and/or exercise performance [6,7]. Alternatively, 3g/day (without the creatine loading phase) can be adopted and will saturate intramuscular creatine stores in ~28days [8]. Relative dosing strategies (0.03 to 0.14g/kg/day) may account for individual differences in body mass [3] and have been shown to be effective over time [9,10].
To date, only a single systematic review involving older adults has been performed that examined the influence of different creatine dosing strategies and resistance training on measures of fat-free mass [11]. Results showed no significant differences between low (≤5g/day) vs. high (>5g/day) doses of creatine, with and without a creatine loading phase, on gains in estimates of fat-free mass. Fat mass was not assessed in this review. The effects of different creatine dosing strategies on measures of body composition in younger adults remains to be elucidated. Beyond dosing strategies, creatine supplementation appears to be more efficacious when combined with resistance training compared to creatine supplementation alone [12]. However, it is worth noting that other types of physical activity, such as high-intensity interval training (i.e. repeated sprints) may also benefit from creatine supplementation [13]. For example, Nemezio et al. found greater gains in fat-free mass following 5days of creatine supplementation (20g/day) in 19 male amateur cyclists [14].
Another gap in the literature involves the efficacy of different forms of creatine. Creatine monohydrate is the most studied and predominant form of creatine often included in dietary supplements [6,15–17]. Based on empirical research, creatine monohydrate undergoes little degradation during the digestive processes and is nearly completely absorbed by muscle tissue, with an approximate retention rate of 99% after oral consumption [18]. However, manufacturers of dietary supplements have introduced alternate forms of purported creatine. The physical and chemical properties of these variants are theorized (not proven) to provide greater bioavailability and efficacy compared to creatine monohydrate [16]. Nevertheless, the available evidence is insufficient to establish the superiority or safety of these various alternate forms of creatine, whether used alone or in combination with other nutrients, compared to creatine monohydrate. The impact of different forms of creatine supplementation on body composition remains to be systematically evaluated.
Therefore, the purpose of this systematic review is to provide a comprehensive evaluation of creatine supplementation on body composition including an analysis of potential modifiers, such as dosing protocols, alternative forms of creatine, and mode of exercise. Further, this systematic review evaluated several components of body composition including body mass, body mass index, and estimates of fat mass, body fat percentage, and fat-free mass. There is animal research showing that creatine supplementation plays an important role in fat bioenergetics and influences whole-body energy expenditure [19–21] which may influence body fat percentage over time. To date, two meta-analyses have been performed showing that the combination of creatine supplementation and resistance training results in very small reductions in body fat percentage compared to resistance training alone [21,22]. Lastly, there is evidence that sex [12] and age [23] differences may exist regarding muscle changes over time, however, the effects on other indices of body composition are unknown. Collectively, this study aimed to systematically review randomized controlled trials (RCTs) evaluating the effects of creatine supplementation on body composition and to determine if the dosing protocol, exercise type, or alternative forms of creatine, as well as sex and age, influence the results.
2. Materials and methods
2.1. Search strategy and study selection
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were selected among the various methods for reporting systematic reviews and meta-analyses, to perform this study [24]. This study has been registered in PROSPERO (CRD42023416349). Up to July 2023, an exhaustive search was conducted in PubMed, Scopus, and ISI Web of Science, as well as other online databases, to identify relevant articles, with no date or language limitation. The following search items in titles and abstracts were used; ((Creatine[Title/Abstract]) AND (“Body Weight”[Title/Abstract] OR “Body Mass Index”[Title/Abstract] OR “Weight Loss”[Title/Abstract] OR Obesity[Title/Abstract] OR “Waist Circumference”[Title/Abstract] OR “Quetelet Index”[Title/Abstract] OR BMI[Title/Abstract] OR “Weight Reduction”[Title/Abstract] OR “Abdominal Obesity”[Title/Abstract] OR “Central Obesity”[Title/Abstract] OR “Visceral Obesity”[Title/Abstract] OR obese[Title/Abstract] OR overweight[Title/Abstract] OR “fat mass”[Title/Abstract] OR “Body Fat”[Title/Abstract])) AND (Intervention[Title/Abstract] OR “Intervention Study”[Title/Abstract] OR “Intervention Studies”[Title/Abstract] OR “controlled trial”[Title/Abstract] OR randomized[Title/Abstract] OR random[Title/Abstract] OR randomly[Title/Abstract] OR placebo[Title/Abstract] OR “clinical trial”[Title/Abstract] OR Trial[Title/Abstract] OR “randomized controlled trial”[Title/Abstract] OR “randomized clinical trial”[Title/Abstract] OR RCT[Title/Abstract] OR blinded[Title/Abstract] OR “double blind”[Title/Abstract] OR “double blinded”[Title/Abstract] OR trial[Title/Abstract] OR trials[Title/Abstract] OR “Pragmatic Clinical Trial”[Title/Abstract] OR “Cross-Over Studies”[Title/Abstract] OR “Cross-Over”[Title/Abstract] OR “Cross-Over Study”[Title/Abstract] OR parallel[Title/Abstract] OR “parallel study”[Title/Abstract] OR “parallel trial”[Title/Abstract] OR OR[Title/Abstract]).
2.2. Eligibility criteria
All studies that met the following criteria were included: 1) RCTs evaluating the effects of creatine supplementation on body composition as an outcome (body mass, body mass index, fat mass, body fat percentage, and fat-free mass) with a control group, 2) studies conducted on adults (≥18years), 3) that received creatine supplementation as an intervention, 4) studies with at least 4days of the intervention period, 5) parallel or crossover designs, 6) studies with outcome reporting at the beginning and the end of the intervention.
2.3. Exclusion criteria
All studies that followed these features were excluded after the full-text assessment: 1) ecological, review, animal, and observational studies, 2) studies executed on individuals younger than 18years of age, and 3) studies without randomization or placebo or control groups.
2.4. Data extraction
The records were screened primarily for eligibility based on the title and abstract. Next, the full text of the studies was assessed for the possibility of being included in this meta-analysis. Ultimately, the following data were extracted: the name of the first author, the year of publication, the location of the study, the study design, the sample size in each group, the characteristics of the subjects such as mean age, sex, and body mass index, the doses of creatine administered for the intervention, the duration of the interventions, the mean changes and standard deviation (SD) of the markers during the study for both the intervention and control groups. When a study provided multiple data at different time points, only the most recent was considered. It is important to acknowledge that in the current study, any references to fat mass and fat-free mass are to their estimation values.
2.5. Quality assessment
The quality of the articles that were qualified was assessed by two separate researchers applying the Cochran scoring method [25]. The risk of bias was evaluated based on seven criteria, which are as follows: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Accordingly, terms such as “Low,” “High,” or “Unclear” were used to estimate each field. Moreover, any dissemblance was elucidated by the corresponding authors.
2.6. Data synthesis and statistical analysis
To identify the overall effect sizes, weighted mean differences (WMD) and the SD of measures were extracted from both intervention and control groups applying the random-effects model following the protocol of DerSimonian And Laird [26]. Moreover, without mean changes reporting, it was calculated by using this formula: mean change=final values−baseline values, and SD changes were calculated by the following formula [24]:
Also, standard errors (SEs), 95% confidence intervals (CIs), and interquartile ranges (IQRs) were converted respectively to SDs using the Hozo et al. protocol [27]. The random-effects model that accounted for between-study variations was applied to detect the overall effect size. Additionally, the Between-studies heterogeneity was checked by Cochran’s Q test and measured by using the I-squared statistic (I2) [28]. I2 >40% or p-values <0.05 were considered significant between-studies heterogeneity. Furthermore, to check potential sources of heterogeneity [29], subgroup analyses were conducted following the preplanned criteria, including study duration (≤30days vs. >30days), baselines of body composition indices (body mass index: 18.5–24.9kg/m2 vs. 25.0–29.9kg/m2), supplementation protocols (≤5g/day vs/> 5g/day, with and without loading and with and without maintenance doses), training status (active vs. trained vs. non-active), exercise (aerobic vs. resistance vs. combined vs. no exercise), age (≤40 vs. >40years of age), sex (males vs. females), and creatine type (creatine monohydrate vs. alternative forms of creatine). Moreover, a sensitivity analysis was executed to determine the impact of each specific study on the overall estimation [30]. The possibility of publication bias was checked using Egger’s regression test and the visually inspected funnel plot examination [31]. Meta-regression analysis using the random-effects model was undertaken to investigate the potential association between changes in dose and duration with body composition variables. Statistical analysis was carried out applying STATA, version 11.2 (Stata Corp, College Station, TX). The p-values <0.05 were considered statistically significant in all analyses.
3. Results
3.1. Study selection
As mentioned in Figure 1, at first, an exhaustive systematic search was conducted in online datasets and resulted in finding 4831 studies. Then, 1241 studies were identified as duplicates, and 3292 unrelated studies were removed after a comprehensive assessment of the titles and abstracts. Moreover, 157 studies without desired data reporting were excluded following the full-text evaluation of the studies. Finally, according to the inclusion criteria, 143 studies were identified.
3.2. Study characteristic
Ultimately, 143 qualified articles with 172 study arms were included, with 3655 participants (2069 in the intervention group and 1922 in the control group). All included studies had the publication date of between 1993 and 2023. The duration of the intervention in all included trials was from four days [32] to 365 [33] days. The sample size of all studies in this meta-analysis varied from 6 [34] to 109 [33] participants. Moreover, the design of 124 studies was parallel RCT [9,32,33,35–156], and the design of 19 was crossover [34,81,157–173]. The qualified studies were mainly conducted in the USA [9,32,38,39,42,43,45–47,51–53,55–57,60–63,66–69,74,77,78,81,84,86,87,89,91,93,95,97,101,103,105,107–109,111,113,114,116–118,120,124,126,137,138,147,148,152,153,157,160,166,167,169,170,173], the UK [71,85,102,133,142,158,165], Sweden [35], Iran [112,121,143], Australia [41,44,70,76,98,99], France [36,40], Belgium [37,48,65,159,162], Estonia [34,128], Japan [49,82], Netherland [50,139,156], Canada [54,59,64,72,80,90,96,106,130–132,134,145,149,163], Norway [58], Germany [88,92,104,161,168], Poland [75,119], Denmark [73], Thailand [79], Spain [83], Switzerland [164], Portugal [94], Brazil [33,100,115,123,125,127,129,141,144,146,150,155,172], Scotland [174], Italy [110], Mexico [171], Finland [122,136], New Zealand [135], and Turkey [140]. Twenty-one studies were performed on females [33,37,51,52,55,70,77,81,90,94,95,103,115,122,124,125,130,132,138,140,173], 81 studies on males [9,32,34,35,38,39,42,45–50,56–58,60–64,66–69,71,73,75,76,78,79,82–84,88,89,93,96,98–101,104–112,114,118–120,123,126–129,136,137,139,143–145,147,148,150,151,156–158,160,165–167,169,171], and the others were conducted on both [36,40,44,53,54,59,65,72,74,80,85–87,91,92,97,102,116,117,121,131,133–135,141,142,146,149,153–155,161–164,168,170,172]. The characteristics of the included studies are indicated in Table 1.
Table 1.
Studies | Country | Study Design | Training background/health status | Sample size | Trial Duration (d) | Mean Age | Mean BMI | Intervention | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IG | CG | IG | CG | IG | CG | Loading | Creatine Type | How to use | Type of exercise | Control group | |||||
Balsom et al. 1993 | Sweden | parallel, PC, DB | 18 trained males/healthy | 9 | 9 | 6 | 25.6 | 27.3 | NR | NR | Just loading | CrM | 20g/d for 6days | AT | Glucose |
Mujika et al. 1996 | France | parallel, PC, DB | 20 trained male and female swimmers/healthy | 10 | 10 | 5 | NR | NR | NR | NR | Just loading | CrM | 20g/d for 5days | AT | Lactose |
Terrillion et al. 1997 | USA | crossover, PC, DB | 24 trained male runners/healthy | 12 | 12 | 5 | 21 | 21 | NR | NR | Just loading | CrM | 20g/d for 5days | AT | Sucrose |
Vanderberghe et al. 1997 | Belgium | parallel, PC, DB | 19 not trained females/healthy | 10 | 9 | 74 | NR | NR | NR | NR | loading+long maintenance | CrM | 20g/d for 4days +5g/d for 70days | RT | Maltodextrin |
Noonan et al. 1998a | USA | parallel, PC, DB | 20 trained male college athletes/healthy | 13 | 7 | 56 | 19.4 | 20.4 | NR | NR | loading+long maintenance | CrM | 20g/d for 5days +8.5g/d for 51days | CT | Dextrose |
Noonan et al. 1998b | USA | parallel, PC, DB | 19 trained male college athletes/healthy | 13 | 6 | 56 | 19.7 | 20.4 | NR | NR | High dose maintenance | CrM | 20g/d for 5days +26.1g/d for 51days | CT | Dextrose |
Kreider et al. 1998 | USA | parallel, PC, DB | 25 trained male football player/healthy | 11 | 14 | 28 | NR | NR | NR | NR | High dose maintenance | CrM | 15.75g/d for 28days | RT | Phosphagen HP (glucose, taurine, disodium phosphate, potassium phosphate) |
Oopik et al. 1998 | Estonia | cross over,PC | 6 trained male karate athletes/healthy | 6 | 6 | 5 | 22.5 | 22.5 | NR | NR | Just loading | CrM | 20g/d for 5days | CT | Glucose |
Maganaris et al. 1998 | UK | crossover, PC, DB | 10 active males/healthy | 10 | 10 | 5 | 28 | 28 | NR | NR | Just loading | CrM | 10g/d for 5days | RT | Glucose polymer |
Bermon et al. 1998a | France | parallel, PC, DB | 16 not trained males and females/healthy | 8 | 8 | 52 | 71.8 | 69.3 | 25.4 | 26.4 | loading+long maintenance | CrM | 20g/d for 5days +3g/d for 47days | NO | Glucose |
Bermon et al. 1998b | France | parallel, PC, DB | 16 not trained males and females/healthy | 8 | 8 | 52 | 71 | 69.3 | 24.7 | 25 | loading+long maintenance | CrM | 20g/d for 5days +3g/d for 47days | RT | Glucose |
Vukovich et al. 1998a | USA | parallel,PC,DB | 24 active males/healthy | 12 | 12 | 21 | 23.3 | 21.3 | NR | NR | Loading+short maintenance | CrM | 20g/d for 5days +10g/d for 16days | RT | CHP (solid form) |
Vukovich et al. 1998b | USA | parallel,PC,DB | 24 active males/healthy | 12 | 12 | 21 | 21.9 | 22.3 | NR | NR | Loading+short maintenance | CrM | 20g/d for 5days +10g/d for 16days | RT | CHO (powder form) |
Kelly et al. 1998 | Australia | parallel, PC | 18 trained males/healthy | 9 | 9 | 26 | 25.5 | 28.1 | NR | NR | Loading+short maintenance | CrM | 20g/d for 5days +5g/d for 21days | RT | Glucose |
Mckenna et al.1999 | Australia | parallel, PC, DB | 14 active males and females/healthy | 7 | 7 | 5 | 19 | 21 | NR | NR | Just loading | CrM | 30g/d for 5days | NR | Dextrose |
Francaux et al. 1999 | Belgium | parallel, PC, DB | 18 not trained males/healthy | 8 | 10 | 63 | NR | NR | NR | NR | loading+long maintenance | CrM | 21g/d for 5days +3g/d for 58days | RT | Maltodextrin |
Rawson et al. 1999 | USA | parallel, PC, DB | 20 not trained males/healthy | 10 | 10 | 30 | 66.7 | 66.9 | NR | NR | Loading+short maintenance | CrM | 20g/d for 10days +4g/d for 20days | NR | Dextrose |
Pearson et al. 1999 | USA | parallel, PC, DB | 16 trained male football players/healthy | 8 | 8 | 70 | NR | NR | NR | NR | maintenance | CrM | 5g/d for 70days | RT | Placebo capsules (NR) |
Leenders et al. 1999a | USA | parallel, PC,DB | 18 trained male swimmers/healthy | 9 | 9 | 14 | 19.8 | 19 | NR | NR | Loading+short maintenance | NR | 20g/d for 6days +10g/d for 8days | AT | Maltodextrin solution 6% |
Leenders et al. 1999b | USA | parallel,PC,DB | 14 trained female swimmers/healthy | 7 | 7 | 14 | 19.1 | 19.4 | NR | NR | Loading+short maintenance | NR | 20g/d for 6days +10g/d for 8days | AT | Maltodextrin solution 6% |
Peeters et al. 1999a | USA | parallel, PC, DB | 18 active males/healthy | 11 | 7 | 42 | NR | NR | NR | NR | loading+long maintenance | CrM | 20g/d for 3days +10g/d for 39days | RT | Maltodextrin powder |
Peeters et al. 1999b | USA | parallel, PC, DB | 16 active males/healthy | 9 | 7 | 42 | NR | NR | NR | NR | loading+long maintenance | Cr phosphate | 20g/d for 3days +10g/d for 39days | RT | Maltodextrin powder |
Haff et al. 2000 | USA | parallel, PC, DB | 36 trained male and female collegiate track-and-field athletes/healthy | 15 | 21 | 42 | 19.9 | 19.9 | NR | NR | High dose maintenance | CrM | 22.41g/d for 42days | RT | Rice flour and magnesium stearate |
Schedel et al. 2000 | Japan | parallel, PC, DB | 10 trained males by endurance or resistance exercise/healthy | 5 | 5 | 7 | 24 | 23 | 22.4 | 22.8 | Just loading | CrM | 30g/d for 7days | CT | Identical beverage without Cr |
Deutekom et al. 2000 | Netherlands | parallel, PC, DB | 23 trained male rowers/healthy | 11 | 12 | 6 | NR | NR | NR | NR | Just loading | CrM | 20g/d for 6days | CT | Maltodextrin |
Mihic et al. 2000 | Canada | parallel, PC, DB | 30 not trained males and females/healthy | 15 | 15 | 5 | 22.4 | 22.4 | NR | NR | Just loading | CrM | 20g/d for 5days | NR | Glucose polymer |
Hamilton et al. 2000 | USA | parallel, PC, DB | 24 trained females/healthy | 11 | 13 | 7 | 22.5 | 23.9 | NR | NR | Just loading | CrM | 25g/d for 7days | RT | Polycose |
Larson-Meyer et al. 2000 | USA | parallel, PC, DB | 13 trained females/healthy | 7 | 6 | 91 | 19.3 | 19 | NR | NR | loading+long maintenance | CrM | 15g/d for 7days +5g/d for 84days | CT | cool water+PowerAde powder |
Volek et al. 2000 | USA | parallel, PC, DB | 19 trained males/healthy | 10 | 9 | 84 | 25.6 | 25.4 | NR | NR | loading+long maintenance | CrM | 25g/d for 7days +5g/days for 77days | RT | Cellulose powder |
Becque et al. 2000 | USA | parallel,PC,DB | 23 active males/healthy | 10 | 13 | 42 | NR | NR | NR | NR | loading+long maintenance | CrM | 20g/day for 5days +2g/day for 37days | RT | Flavored, sucrose drink |
Brenner et al. 2000 | USA | parallel, PC, DB | 16 trained female lacrosse players/healthy | 7 | 9 | 35 | 18.1 | 19.5 | NR | NR | Loading+short maintenance | CrM | 20g/d for 7days +2g/d for 28days | CT | Sucrose |
Skare et al. 2001 | Norway | parallel, PC, SB | 18 trained male sprinters/healthy | 9 | 9 | 5 | NR | NR | NR | NR | Just loading | CrM | 20g/d for 5days | CT | Glucose |
Green et al. 2001 | USA | parallel, PC, DB | 19 trained male recreational athletes/healthy | 9 | 10 | 6 | 26.3 | 24.1 | NR | NR | Just loading | CrM | 20 gr/d for 6days | NR | Sucrose and maltodextrin |
Rockwell et al. 2001 | USA | parallel, PC, DB | 16 trained males/healthy | 8 | 8 | 4 | 20.5 | 21.6 | NR | NR | Just loading | CrM | 20g/d for 4days | RT | Sucrose+Hypo energy diet |
Op t Eijnde et al. 2001 | Belgium | crossover, PC, DB | 11 not trained males/healthy | 11 | 11 | 5 | 20.7 | 20.7 | NR | NR | Just loading | CrM | 20g/d for 5days | RT | Maltodextrin plus citrate |
Bemben et al. 2001 | USA | parallel, PC, DB | 17 trained male football players/healthy | 9 | 8 | 63 | 19.4 | 19.3 | NR | NR | loading+long maintenance | CrM | 20g/d for 5days +5g/d for 58days | CT | Glucose solution (containing sodium phosphate, exact protocol as the Cr group) |
Chrusch et al. 2001 | Canada | parallel, PC, DB | 30 not trained males/healthy | 16 | 14 | 84 | 70.4 | 71.1 | 27.9 | 25.7 | loading+long maintenance | CrM | 26.4g/d for 5days +6.2g/d for 79days | RT | CHO mixture |
Kern et al. 2001 | USA | parallel, PC, DB | 19 active males/healthy | 9 | 10 | 28 | 22.4 | 22.2 | NR | NR | Loading+short maintenance | CrM | 21g/d for 5days +10g/d for 23days | CT | Phosphagen HP matrix |
Parise et al. 2001a | Canada | parallel, PC, DB | 14 active females/healthy | 7 | 7 | 8 | NR | NR | NR | NR | Loading+short maintenance | CrM | 20g/d for 5days +5g/d for 3days | CT | Glucose polymer |
Parise et al. 2001b | Canada | parallel, PC, DB | 13 active males/healthy | 7 | 6 | 8 | NR | NR | NR | NR | Loading+short maintenance | CrM | 20g/d for 5days +5g/d for 3days | CT | Glucose polymer |
Wilder et al. 2001a | USA | parallel,PC,DB | 13 trained male football players/healthy | 8 | 5 | 70 | NR | NR | NR | NR | maintenance | CrM | 3g/d for 70days | CT | Dextrose |
Wilder et al. 2001b | USA | parallel,PC,DB | 12 trained male football players/healthy | 8 | 4 | 70 | NR | NR | NR | NR | loading+long maintenance | CrM | 20g/d for 7days +5g/d for 63days | CT | Dextrose |
Willoughby et al. 2001 | USA | parallel, PC, DB | 16 not trained males/healthy | 8 | 8 | 84 | NR | NR | NR | NR | maintenance | CrM | 6g/d for 84days | RT | Dextrose |
Hespel et al. 2001 | Belgium | parallel, PC, DB | 22 not trained males and females/healthy | 11 | 11 | 84 | NR | NR | NR | NR | ND | CrM | 20g/d for 14days +15g/d for 21days +5g/d for 35days | RT | Maltodextrin |
Coxe et al. 2002 | Australia | parallel, PC, DB | 12 trained female soccer players/healthy | 6 | 6 | 6 | NR | NR | NR | NR | Just loading | CrM | 20g/d for 6days | AT | glucose polymer |
Gotshalk et al. 2002 | USA | parallel, PC, DB | 18 not trained males/healthy | 10 | 8 | 7 | 65.4 | 65.7 | NR | NR | Just loading | CrM | 25.32g/d for 7days | NR | Cellulose |
Kilduff et al. 2002 | UK | parallel, PC, DB | 32 trained males/healthy | 21 | 11 | 5 | 24.5 | 24.5 | NR | NR | Just loading | CrM | 20g/d for 5days | RT | Glucose polymer |
Wilder et al. 2002a | USA | parallel, PC, DB | 13 trained males/healthy | 8 | 5 | 70 | 18.8 | 19.2 | NR | NR | maintenance | CrM | 3g/d for 70days | CT | Dextrose |
Wilder et al. 2002b | USA | parallel, PC, DB | 12 trained males/healthy | 8 | 4 | 70 | 18.8 | 19.2 | NR | NR | loading+long maintenance | CrM | 20g/d for 7days +5g/d for 63days | CT | Dextrose |
Walter et al. 2002 | Germany | crossover, PC, DB | 34 not trained males and females/DM1 | 34 | 34 | 56 | 44.13 | 44.13 | NR | NR | loading+long maintenance | CrM | 10.6g/d for10 days +5.3g/d for 46days | NO | Microcrystalline cellulose |
Huso et al. 2002 | USA | crossover, PC, DB | 10 active males/healthy | 10 | 10 | 21 | NR | NR | NR | NR | Loading+short maintenance | CrM | 20g/d for 4days +2g/d for 17days | RT | Maltodextrin |
Warber et al. 2002 | USA | parallel, PC, DB | 26 active males/healthy | 13 | 13 | 5 | 30.5 | 33.4 | NR | NR | Just loading | CrM | 24g/d for 5days | NR | Identical sports bars |
Kutz et al. 2003 | USA | parallel, PC, DB | 17 not trained males/healthy | 9 | 8 | 28 | NR | NR | NR | NR | High dose maintenance | CrM | 30g/d for 14days +15g/d for 14days | RT | Multodextros+rice brane+sucrose |
Vukovich et al. 2003 | USA | control trail | 24 trained males/healthy | 12 | 12 | 7 | NR | NR | NR | NR | Just loading | CrM | 21g/d for 7days | RT | Regular diet |
Lehmkuhl et al. 2003 | USA | parallel,PC,DB | 19 trained male and female young track and field athletes/healthy | 10 | 9 | 56 | 19.4 | 20.1 | NR | NR | loading+long maintenance | CrM | 21.2g/d for 7days +2.1g/d for 49days | CT | Potato starch |
Burke et al. 2003a | Canada | parallel, PC, DB | 18 active male and female young track and field athletes/healthy | 10 | 8 | 56 | 31 | 34 | NR | NR | loading+long maintenance | CrM | 16.8g/d for7 days +4.2g/d for 49days | CT | Maltodextrin |
Burke et al. 2003b | Canada | parallel, PC, DB | 24 active male and female young track and field athletes/healthy | 12 | 12 | 56 | 33 | 32 | NR | NR | loading+long maintenance | CrM | 16.8g/d for7 days +4.2g/d for 49days | CT | Maltodextrin |
Van Loon et al. 2003 | Netherlands | parallel, PC, DB | 19 not trained males/healthy | 9 | 10 | 42 | 20.6 | 21.3 | 20.4 | 21.2 | loading+long maintenance | CrM | 20g/d for 5days +2g/d for 37days | NO | Glucose+Maltodextrin |
Zajac et al.2003 | Poland | parallel, PC, DB | 25 trained male basketball players/healthy | 12 | 13 | 30 | NR | NR | NR | NR | maintenance | CrM | ND | CT | CHO |
Eijnde et al. 2003a | Denmark | parallel,PC,DB | 46 not trained males/healthy | 23 | 23 | 180 | 63.9 | 62.2 | NR | NR | maintenance | CrM | 5g/d for 180days | CT | Placebo capsules (NR) |
Eijnde et al. 2003b | Denmark | parallel,PC,DB | 20 not trained males/healthy | 10 | 10 | 360 | 65.3 | 61.8 | NR | NR | maintenance | CrM | 5g/d for 360days | CT | Placebo tablets (NR) |
Kambis et al. 2003 | USA | parallel, PC, DB | 22 not trained females/healthy | 11 | 11 | 5 | NR | NR | NR | NR | Just loading | CrM | 24.3g/d for 5days | NR | Corn starch |
Brose et al. 2003a | Canada | parallel, PC, DB | 15 not trained males/healthy | 8 | 7 | 98 | 68.7 | 68.3 | NR | NR | maintenance | CrM | 5g/d for 98days | RT | Dextrose |
Brose et al. 2003b | Canada | parallel, PC, DB | 13 not trained females/healthy | 6 | 7 | 98 | 70.8 | 69.9 | NR | NR | maintenance | CrM | 5g/d for 98days | RT | Dextrose |
Watsford et al. 2003 | Australia | parallel, PC, DB | 20 not trained males/healthy | 9 | 11 | 28 | NR | NR | NR | NR | Loading+short maintenance | NR | 20g/d for 7days +10g/d for 21days | NO | Placebo capsules (NR) |
Eckerson et al. 2004 | USA | crossover, PC, DB | 10 active females/healthy | 10 | 10 | 5 | NR | NR | NR | NR | Just loading | Cr citrate | 20 gr/d for 5days | CT | Dextrose powder |
Kinugasa et al. 2004 | Japan | parallel,PC,DB | 12 not trained males/healthy | 6 | 6 | 5 | 22.5 | 22.2 | NR | NR | Just loading | CrM | 20g/d for 5days | NO | Maltodextrin |
Javierre et al. 2004 | Spain | parallel, PC | 19 active males/healthy | 10 | 9 | 5 | NR | NR | NR | NR | Just loading | CrM | 20g/d for 5days | NR | Placebo capsules (NR) |
Volek et al. 2004 | USA | parallel, PC, DB | 17 trained males/healthy | 9 | 8 | 28 | 20.7 | 21.3 | NR | NR | Loading+short maintenance | CrM | 26g/d for 7days +4.33g/d for 21days | RT | Cellulose powder |
Ball SD et al. 2004 | USA | crossover, PC, DB | 10 active males/healthy | 10 | 10 | 21 | NR | NR | NR | NR | Loading+short maintenance | CrM | 20g/d for 4days +2g/d for 17days | RT | Maltodextrin |
Tarnopolosky et al. 2004 | Canada | crossover, PC, DB | 34 not trained males and females/DM1 patients | 34 | 34 | 120 | 41 | 41 | NR | NR | maintenance | CrM | 5g/d for 120days | NO | Dextrose and cellulose fiber |
Taes et al. 2004 | Belgium | crossover, PC, DB | 45 not trained males and females/Hemodialysis patients | 45 | 45 | 28 | 71 | 69 | NR | NR | maintenance | CrM | 2g/d for 28days | NO | Lactose |
Anomasiri et al. 2004 | Thailand | parallel, PC, DB | 38 active males/healthy | 19 | 19 | 7 | NR | NR | NR | NR | ND | CrM | 10g/d for 7days | AT | Orange juice powder |
Eckerson et al. 2005a | USA | parallel, PC, DB | 15 active males/healthy | 10 | 5 | 6 | NR | NR | NR | NR | Just loading | Cr citrate | 20g/d for 6days | CT | Dextrose |
Eckerson et al. 2005b | USA | parallel, PC, DB | 15 active females/healthy | 10 | 5 | 6 | NR | NR | NR | NR | Just loading | Cr citrate | 20g/d for 6days | CT | Dextrose |
Eckerson et al. 2005c | USA | parallel, PC, DB | 15 active males/healthy | 10 | 5 | 6 | NR | NR | NR | NR | Just loading | Cr phosphate | 20g/d for 6days | CT | Dextrose |
Eckerson et al. 2005d | USA | parallel, PC, DB | 15 active females/healthy | 10 | 5 | 6 | NR | NR | NR | NR | Just loading | Cr phosphate | 20g/d for 6days | CT | Dextrose |
Perret et al. 2005 | Switzerland | crossover, PC, DB | 6 trained male and female competitive wheelchair athletes/healthy | 6 | 6 | 6 | 33 | 33 | NR | NR | Just loading | CrM | 20g/d for 6days | AT | Maltodextrin |
Ahmun et al. 2005 | UK | crossover,PC,DB | 14 trained male rugby players/healthy | 14 | 14 | 5 | 20.6 | 20.6 | NR | NR | Just loading | CrM | 20g/d for 5days | CT | Dextrose powder |
Mendell et al. 2005 | USA | parallel, PC, DB | 16 active males and females/healthy | 8 | 8 | 5 | 26 | 26 | NR | NR | Just loading | CrM | 20g/d for 5days | NO | Solka-Floc (cellulose) plus Gatorade |
Fuld et al. 2005 | UK | parallel, PC, DB | 25 not trained males and females/patients with COPD | 14 | 11 | 84 | 61.7 | 63.7 | 23.2 | 24.3 | loading+long maintenance | CrM | 17.1g/d for 14days+5.7 gr/d for 70days | CT | Glucose polymer |
Hoffman et al. 2005 | USA | parallel, PC, DB | 40 not trained males/healthy | 20 | 20 | 6 | 21.7 | 21.1 | NR | NR | ND | CrM | 6 gr/d for 6days | NR | Cellulose powder and methylcellulose |
Kuethe et al. 2006 | Germany | crossover, PC, DB | 13 not trained males and females/congestive heart failure patients | 13 | 13 | 42 | 58.2 | 58.2 | NR | NR | High dose maintenance | CrM | 20g/day for 42days | NO | Placebo capsules (NR) |
Hille et al. 2006 | USA | crossover, PC, DB | 11 trained males/healthy | 11 | 11 | 7 | NR | NR | NR | NR | Just loading | CrM | 21.6g/day for 7days | NR | Placebo capsules (NR) |
Norman et al. 2006 | Germany | parallel, PC, DB | 31 not trained males and females/Patients with colorectal cancer | 16 | 15 | 56 | 65.1 | 61.61 | 25.13 | 24.62 | loading+long maintenance | CrM | 20g/day for 7days +5g/d for 49days | NR | Cellulose |
Ferguson et al. 2006 | Canada | parallel, PC, DB | 26 trained females/healthy | 13 | 13 | 70 | NR | NR | NR | NR | loading+long maintenance | CrM | 19.71g/d for 7days+1.97 gr/d for 63days | RT | Placebo capsules (NR) |
Pluim et al. 2006 | Germany | parallel,PC,DB | 24 trained male tennis players/healthy | 14 | 10 | 34 | 22.5 | 22.8 | NR | NR | Loading+short maintenance | CrM | 22.1g/d for 6days +2.2g/d for 28days | AT | Maltodextrin and dextrose |
Rogers et al. 2006 | USA | parallel, PC, DB | 30 not trained males and females/healthy | 15 | 15 | 84 | NR | NR | NR | NR | maintenance | CrM | 3g/d for 84days | RT | Maltodextrin |
Hoffman et al. 2006 | USA | parallel, PC, DB | 33 trained male football players/healthy | 17 | 16 | 70 | NR | NR | NR | NR | maintenance | CrM | 10.5g/d for 70days | RT | Dextrose |
Smith et al. 2007 | USA | parallel, PC, DB | 15 trained females/healthy | 7 | 8 | 5 | 22.4 | 22.3 | NR | NR | Just loading | Cr citrate | 20g/d for 5days | NR | Dextrose |
Stout et al. 2007 | USA | crossover, PC, DB | 15 not trained males and females/healthy | 15 | 15 | 14 | 74.5 | 74.5 | NR | NR | Loading+short maintenance | Cr citrate | 20g/d for 7days +10g/d for 7days | NO | Flavored powder blend |
Silva et al. 2007 | Portugal | parallel, PC, DB | 16 trained female competitive swimmers/healthy | 8 | 8 | 21 | 16.3 | 15.7 | NR | NR | High dose maintenance | CrM | 20g/d for 21days | AT | Maltodextrin solution 6% |
Wright et al. 2007 | USA | crossover, PC, DB | 10 active male s/healthy | 10 | 10 | 7 | 25.7 | 25.7 | NR | NR | Just loading | CrM | 20g/d for 7days | AT | Sucrose and maltodextrin drink |
De Souza junior et al. 2007 | Brazil | parallel, PC, DB | 18 active male s/healthy | 9 | 9 | 42 | 25 | 23 | NR | NR | loading+long maintenance | CrM | 30g/d for 7days +5g/d for 35days | RT | Maltodextrin |
Cribb et al. 2007a | Australia | parallel, PC, DB | 15 active male s/healthy | 8 | 7 | 77 | 25 | 24 | NR | NR | loading+long maintenance | CrM | 25g/d for 7days +8.4g/d for 70days | RT | CHO |
Cribb et al. 2007b | Australia | parallel, PC, DB | 11 active male s/healthy | 6 | 5 | 77 | 25 | 24 | NR | NR | loading+long maintenance | CrM | 25g/d for 7days +8.4g/d for 70days | RT | Whey protein |
Hass et al. 2007 | USA | parallel, PC, DB | 20 not trained males and females/healthy | 10 | 10 | 84 | 62.8 | 62.2 | NR | NR | loading+long maintenance | CrM | 20g/d for 5days +5g/d for 79days | RT | Lactose monohydrate |
Chilibeck et al. 2007 | Canada | parallel, PC, DB | 18 trained male rugby union football players/healthy | 9 | 9 | 56 | 27 | 26 | NR | NR | maintenance | CrM | 9.5 d/d for 56days | CT | Glucose |
Cribb et al. 2007 | Australia | parallel, PC, DB | 21 active males/healthy | 10 | 11 | 70 | 26 | 26 | NR | NR | maintenance | CrM | 8.9g/d for 70days | RT | PRO-CHO supplement |
Walter et al. 2008 | USA | parallel, PC, DB | 16 trained males/healthy | 8 | 8 | 5 | 26.1 | 23.1 | NR | NR | Just loading | Cr citrate | 20g/d for 5days | NR | Fructose powder |
Eckerson et al. 2008 | USA | parallel, PC, DB | 32 active males/healthy | 17 | 15 | 30 | 22 | 20 | NR | NR | maintenance | Cr citrate | 5g/day for 30days | CT | Dextrose |
Gotshalk et al. 2008 | USA | parallel, PC, DB | 27 not trained females/healthy | 15 | 12 | 7 | 63.31 | 62.98 | NR | NR | Just loading | CrM | 20.13g/d for 7days | NR | Cellulose |
Deacon et al. 2008 | UK | parallel, PC, DB | 80 not trained males and females/Participants with COPD | 38 | 42 | 54 | 67.6 | 68.3 | 28.1 | 25.7 | loading+long maintenance | CrM | 20g/d for 5days+3.76 gr/d for 49days | CT | Lactose |
Eliot et al. 2008 a | USA | parallel, PC, DB | 20 not trained males/healthy | 10 | 10 | 98 | NR | NR | NR | NR | maintenance | CrM | 2.14g/d for 98days | RT | Sport drink |
Eliot et al. 2008 b | USA | parallel, PC, DB | 22 not trained males/healthy | 11 | 11 | 98 | NR | NR | NR | NR | maintenance | CrM | 2.14g/d for 98days | RT | whey protein +Sport drink |
Little et al. 2008 | Canada | parallel, PC, DB | 23 active males/healthy | 11 | 12 | 10 | 22.8 | 22.8 | NR | NR | maintenance | NR | 8g/d for 10days | NR | Sucrose-based fruit punch |
Jager et al. 2008 a | Germany | parallel, PC, DB | 25 trained male athletes/healthy | 16 | 9 | 28 | 26.8 | 26.3 | NR | NR | maintenance | other | 5g/d for 28days | NR | Placebo tablets |
Jager et al. 2008 b | Germany | parallel, PC, DB | 24 trained male athletes/healthy | 16 | 8 | 28 | 26.7 | 26.3 | NR | NR | maintenance | Cr citrate | 5 gr/d for 28days | NR | Placebo tablets |
Sakkas et al. 2009 | USA | parallel, PC, DB | 38 not trained males/HIV positive participants | 19 | 19 | 98 | 44 | 44 | 23.7 | 23.7 | loading+long maintenance | CrM | 20g/d for 5days +4.8g/d for 93days | RT | Placebo capsules (NR) |
Bazzucchi et al. 2009 | Italy | parallel,PC,DB | 16 trained males/healthy | 8 | 8 | 5 | 26.7 | 23.3 | 23.3 | 24.2 | Just loading | NR | 20g/d for 5days | NR | Maltodextrin |
Spillane et al. 2009a | USA | parallel, PC, DB | 15 active males/healthy | 10 | 5 | 48 | 20.36 | 20.16 | NR | NR | loading+long maintenance | CrM | 20g/d for 5days +5g/d for 42days | RT | Maltodextrin |
Spillane et al. 2009b | USA | parallel, PC, DB | 15 active males/healthy | 10 | 5 | 48 | 20.83 | 20.16 | NR | NR | loading+long maintenance | other | 20g/d for 5days +5g/d for 42days | RT | Maltodextrin |
Herda et al. 2009a | USA | parallel, PC, DB | 18 trained males/healthy | 13 | 5 | 30 | NR | NR | NR | NR | maintenance | CrM | 5g/d for 30days | CT | Cellulose |
Herda et al. 2009b | USA | parallel, PC, DB | 19 trained males/healthy | 14 | 5 | 30 | NR | NR | NR | NR | maintenance | other | 1.25g/d for 30days | CT | Cellulose |
Herda et al. 2009c | USA | parallel, PC, DB | 21 trained males/healthy | 16 | 5 | 30 | NR | NR | NR | NR | maintenance | other | 2.50g/d for 30days | CT | Cellulose |
Fukuda et al. 2010a | USA | parallel, PC, DB | 24 active males/healthy | 12 | 12 | 5 | NR | NR | NR | NR | Just loading | Cr citrate | 20g/d for 5days | CT | Dextrose |
Fukuda et al. 2010b | USA | parallel, PC, DB | 26 active females/healthy | 12 | 14 | 5 | NR | NR | NR | NR | Just loading | Cr citrate | 20g/d for 5days | CT | Dextrose |
Hickner et al. 2010 | USA | parallel, PC, DB | 12 trained males/healthy | 6 | 6 | 28 | 25.5 | 29 | NR | NR | maintenance | CrM | 3 gr/d for 28days | AT | dry milk and orange-flavored carbohydrate |
Saremi et al. 2010 | Iran | parallel, PC, DB | 16 not trained males/healthy | 8 | 8 | 56 | 23.85 | 22.28 | NR | NR | loading+long maintenance | CrM | 23.3g/d for 7days +3.88g/d for 49days | RT | Cellulose |
Camic et al. 2010 | USA | parallel, PC, DB | 22 active males/healthy | 10 | 12 | 28 | NR | NR | NR | NR | maintenance | other | 5g/d for 28days | NO | Maltodextrin |
Smith et al. 2011a | USA | parallel, PC, DB | 27 active males/healthy | 13 | 14 | 5 | NR | NR | NR | NR | Just loading | Cr citrate | 20g/d for 5days | NR | Fructose powder |
Smith et al. 2011b | USA | parallel, PC, DB | 28 active females/healthy | 14 | 14 | 5 | NR | NR | NR | NR | Just loading | Cr citrate | 20g/d for 5days | NR | Fructose powder |
Neves JR et al. 2011 | Brazil | parallel, PC, DB | 24 not trained females/Postmenopausal women with knee osteoarthritis | 13 | 11 | 84 | 58 | 56 | 28.5 | 29.7 | loading+long maintenance | CrM | 20g/d for 5days +5g/d for 79days | RT | Dextrose |
Rawson et al. 2011 | USA | parallel, PC, DB | 20 not trained males and females/healthy | 10 | 10 | 42 | 21 | 20.5 | 25.1 | 25.9 | maintenance | CrM | 2.2g/d for 42days | NR | Placebo capsules (NR) |
Taylor et al. 2011 | USA | parallel, PC, DB | 29 trained males/healthy | 14 | 15 | 56 | 21 | 19.8 | NR | NR | maintenance | CrM | 5g/d for 56days | RT | Dextrose |
Mohebbi et al. 2012 | Iran | parallel, PC, DB | 17 trained male and female young soccer players/healthy | 8 | 9 | 7 | 17.38 | 17 | NR | NR | Just loading | CrM | 20g/d for 7days | AT | Glucose polymer |
Zuniga et al. 2012 | USA | parallel, PC, DB | 22 not trained males/healthy | 10 | 12 | 7 | NR | NR | NR | NR | Just loading | CrM | 20g/d for 7days | NO | Maltodextrin powder |
Pericario et al. 2012 | Brazil | parallel, PC, DB | 18 trained male handball athletes/healthy | 9 | 9 | 32 | 17.1 | 17.1 | NR | NR | Loading+short maintenance | CrM | 20g/d for 5days +5g/d for 27days | RT | Maltodextrin |
Sterkowicz et al. 2012 | Poland | parallel, PC, DB | 10 trained males Judaists/healthy | 5 | 5 | 42 | 22 | 20.4 | 22.27 | 26.92 | maintenance | other | 4.8g/d for 42days | CT | Placebo capsules (NR) |
Montes De Oca et al. 2013 | Mexico | crossover, PC, DB | 10 trained male TKD practitioners/healthy | 10 | 10 | 42 | NR | NR | NR | NR | maintenance | CrM | 3.4g/d for 42days | CT | Maltodextrin |
Aguiar et al. 2013 | Finland | parallel, PC, DB | 18 not trained females/healthy | 9 | 9 | 84 | 64 | 65 | NR | NR | maintenance | CrM | 5.0g/d for 84days | RT | Maltodextrin |
Cooke et al. 2014 | USA | parallel, PC, DB | 20 not trained males/healthy | 10 | 10 | 84 | 61.4 | 60.7 | NR | NR | loading+long maintenance | CrM | 20g/d for 7days +8.8g/d for 77days | RT | CHO |
Gualano et al. 2014a | Brazil | parallel, PC, DB | 30 not trained females/postmenopausal with osteopenia or osteoporosis | 15 | 15 | 166 | 66.1 | 66.3 | 27.1 | 26.8 | loading+long maintenance | CrM | 20g/d for 5days +5g/d for 161days | NO | Dextrose |
Gualano et al. 2014b | Brazil | parallel,PC,DB | 30 not trained females/postmenopausal with osteopenia or osteoporosis | 15 | 15 | 166 | 67.1 | 63.6 | 28 | 28.2 | loading+long maintenance | CrM | 20g/d for 5days +5g/d for 161days | RT | Dextrose |
Kresta et al. 2014(a) | USA | parallel, PC, DB | 15 active females/healthy | 8 | 7 | 28 | 21.5 | 21.5 | NR | NR | Loading+short maintenance | CrM | 18.3g/d for 7days +6.1g/d for 21days | CT | Maltodextrin and dextrose |
kresta et al. 2014(b) | USA | parallel, PC, DB | 17 active females/healthy | 9 | 8 | 28 | 21.5 | 21.5 | NR | NR | Loading+short maintenance | CrM | 17.7g/d for 7days +5.9g/d for 21days | CT | Maltodextrin and dextrose |
Hayashi et al. 2014 | Brazil | crossover, PC, DB | 15 not trained males and females/Systemic lupus erythematosus (C-SLE) patients | 15 | 15 | 84 | NR | NR | NR | NR | maintenance | CrM | 5.34g/d for 84days | NO | Dextrose |
Nemezio. et al. 2015 | Brazil | parallel, PC, DB | 19 active males/healthy | 10 | 9 | 5 | 36 | 33 | NR | NR | Just loading | CrM | 20g/d for 5days | AT | Dextrose |
Aedma et al. 2015 | Estonia | parallel, PC, DB | 20 trained male wrestlers/healthy | 10 | 10 | 5 | NR | NR | NR | NR | Just loading | CrM | 24.8g/d for 5days | CT | Glucose gelatin capsules |
Lobo et al. 2015 | Brazil | parallel, PC, DB | 109 not trained females/postmenopausal osteogenic women | 56 | 53 | 365 | 58 | 58 | 27.6 | 27.5 | maintenance | CrM | 1g/d for 365days | NO | Dextrose |
Candow et al. 2015a | Canada | parallel, PC, DB | 21 not trained males and females/healthy | 15 | 6 | 224 | 53 | 57 | 26.5 | 26.8 | maintenance | CrM | 7.7g/d for 224days | RT | Maltodextrin (Corn-starch) |
Candow et al. 2015b | Canada | parallel, PC, DB | 18 not trained males and females/healthy | 12 | 6 | 224 | 55 | 57 | 29 | 26.8 | maintenance | CrM | 8.7g/d for 224days | RT | Maltodextrin (Corn-starch) |
Chilibeck et al. 2015 | Canada | parallel, PC, DB | 33 not trained females/healthy | 15 | 18 | 364 | 57 | 57 | NR | NR | maintenance | CrM | 6.9g/d for 364days | RT | Maltodextrin |
Deminice et al. 2015 | Brazil | parallel, PC, DB | 13 trained males/healthy | 7 | 6 | 7 | 18.5 | 18.3 | 22.1 | 23.2 | Just loading | CrM | 22g/d for 7days | AT | Maltodextrin |
Wilkinson et al. 2016 | UK | parallel, PC, DB | 35 not trained males and females/patients with stable RA | 15 | 20 | 84 | 63 | 57.2 | 24.7 | 27.8 | loading+long maintenance | CrM | 20g/d for 5days +3g/d for 77days | NO | Flavored drink powder |
Forbes et al. 2016 | Canada | parallel, PC, DB | 17 active females/healthy | 9 | 8 | 28 | 23.8 | 22.4 | NR | NR | Loading+short maintenance | CrM | 19.32g/d for 5days +6.44g/days for 23days | AT | Maltodextrin |
Pinto et al. 2016 | Brazil | Parallel, PC, DB | 27 not trained males and females/healthy | 13 | 14 | 84 | 67.4 | 67.1 | NR | NR | maintenance | CrM | 5g/d for 84 day | RT | Maltodextrin powder |
Collins et al. 2016 | New Zealand | parallel, PC, DB | 16 not trained males and females/healthy | 9 | 7 | 98 | 70 | 69 | 30.9 | 30.1 | maintenance | CrM | 5g/d for 98days | RT | Maltodextrin+whey |
Johannsmeyer et al.2016 | Canada | parallel, PC, DB | 31 not trained males and females/healthy | 14 | 17 | 84 | 58 | 57.6 | NR | NR | maintenance | CrM | 7.83g/d for 84days | RT | Maltodextrin |
Backx et al. 2017 | Finland | parallel, PC, DB | 30 not trained males/healthy | 15 | 15 | 21 | 23 | 23 | 23 | 23.5 | Loading+short maintenance | CrM | 20g/d for 5days+5 gr/day for 16days | NO | Maltodextrin and dextrose monohydrate |
Wilborn et al. 2017 | USA | parallel, PC, DB | 17 trained females/healthy | 8 | 9 | 56 | 22 | 20 | 23.2 | 23.8 | maintenance | CrM | 5g/d for 56days | RT | Whey protein |
Karamat et al. 2017 | Netherlands | parallel, PC, TB | 16 not trained males/healthy | 8 | 8 | 7 | NR | NR | 22.1 | 24.2 | ND | NR | 5g/d for 7days | NR | Placebo capsules (NR) |
Atakan et al. 2018 | Turkey | parallel, PC, DB | 30 trained female futsal players/healthy | 15 | 15 | 7 | 19.6 | 20.7 | 22.17 | 19.83 | Just loading | CrM | 14.5g/d for 7days | AT | Maltodextrin |
Wang et al. 2018 | USA | parallel, PC, DB | 30 trained male athletes/healthy | 15 | 15 | 28 | 20 | 20 | NR | NR | Loading+short maintenance | CrM | 20g/d for 6days +2g/d for 22days | CT | Carboxymethyl cellulose powder plus dextrose |
Vanbavel et al. 2019 | Brazil | parallel, PC, DB | 49 active males and females/healthy | 31 | 18 | 21 | 33 | 32 | 23.3 | 22.9 | maintenance | CrM | 5g/d for 21days | NR | Maltodextrin |
Arazi et al. 2019 | Iran | parallel, PC, DB | 16 not trained males/healthy | 8 | 8 | 42 | 20.87 | 20.37 | NR | NR | loading+long maintenance | other | 20g/d for 5days +5g/d for 37days | RT | Rice flour |
Almeida et al. 2020 | Brazil | parallel, PC, DB | 18 active males/healthy | 9 | 9 | 7 | 22.7 | 24.2 | NR | NR | Just loading | CrM | 24.2g/d for 7days | RT | Dextrose |
Marini et al. 2020 | Brazil | parallel, PC, DB | 28 not trained males and females/hemodialysis patients | 14 | 14 | 28 | 41.86 | 41.79 | 22.76 | 21.93 | Loading+short maintenance | CrM | 20g/d for 7days +5g/d for 21days | NO | Maltodextrin |
Candow et al. 2020 | Canada | parallel, PC, DB | 38 not trained males/healthy | 18 | 20 | 364 | 58 | 56 | NR | NR | maintenance | CrM | 9.3g/d for 364days | RT | Maltodextrin (Corn-starch) |
Delextrat et al. 2020a | UK | parallel, PC, DB | 22 trained male and female team- and racket sport players/healthy | 11 | 11 | 28 | 25.6 | 25.2 | NR | NR | maintenance | CrM | 5g/d for 28days | CT | Rice flour |
Delextrat et al. 2020b | UK | parallel, PC, DB | 22 trained male and female team and racket sport players/healthy | 12 | 10 | 28 | 26 | 24.2 | NR | NR | maintenance | CrM | 5g/d for 28days | CT | Rice flour+beta-alanine |
Anders et al. 2021 | USA | parallel, PC, DB | 22 trained males/healthy | 12 | 10 | 28 | 19.8 | 20.6 | NR | NR | maintenance | CrM | 2.4g/d for 28days | CT | Cellulose |
Pakulak et al. 2021a | Canada | parallel, PC, DB | 10 active males and females/healthy | 5 | 5 | 42 | 22 | 23 | NR | NR | maintenance | CrM | 7.6g/d for 42days | RT | Cellulose powder |
pakulak et al. 2021b | Canada | parallel, PC, DB | 10 active males and females/healthy | 5 | 5 | 42 | 22 | 19 | NR | NR | maintenance | CrM | 7.4g/d for 42days | RT | Cellulose powder |
Bonilla et al. 2021 | USA | parallel, SB | 16 active males/healthy | 8 | 8 | 56 | NR | NR | 23.89 | 25.02 | maintenance | CrM | 7.6g/d for 56days | RT | Cluster-set resistance training (CS-RT) |
Butchart et al. 2022 | Canada | parallel, PC, DB | 8 not trained participants/stroke survivors | 5 | 3 | 70 | 51 | 73 | 29.2 | 27.4 | loading+long maintenance | CrM | 25.4g/d for 7days +8.4g/d for 63days | RT | corn-starch maltodextrin |
Almeida et al. 2022 | Brazil | parallel, PC, DB | 34 active males/healthy | 17 | 17 | 28 | 23.1 | 23.8 | NR | NR | Loading+short maintenance | CrM | 21.9g/d for 7days +2.1g/d for 21days | RT | Dextrose |
Dinan et al. 2022a | USA | parallel, PC, DB | 18 trained male and female athletes/healthy | 12 | 6 | 56 | NR | NR | NR | NR | maintenance | CrM | 5g/d for 56days | RT | maltodextrin |
Dinan et al. 2022b | USA | parallel, PC, DB | 16 trained male and female athletes/healthy | 11 | 5 | 56 | NR | NR | NR | NR | maintenance | CrM | 5g/d for 56days | RT | maltodextrin |
Askow et al. 2022 | USA | parallel, PC, DB | 18 not trained male and female athletes/healthy | 8 | 10 | 14 | 28.5 | 30.3 | 25.8 | 24.7 | maintenance | CrM | 5g/d for 14days | RT | maltodextrin |
Moore et al. 2023a | USA | crossover, PC, DB | 30 active females/healthy | 30 | 30 | 5 | 25.4 | 24.5 | 23.6 | 23.1 | Just loading | CrM | 20g/d for 5days | NR | crystal light |
Moore et al. 2023b | USA | crossover, PC, DB | 30 active females/healthy | 30 | 30 | 5 | 25.4 | 24.5 | 23.6 | 23.1 | Just loading | CrM | 20g/d for 5days | NR | crystal light |
Note: Abbreviations: IG, intervention group; CG, control group; DB, double-blinded; SB, single-blinded; PC, placebo-controlled; CO, controlled; RA, randomized; NR, not reported; F, Female; M, Male; NR, not reported; DM1, Myotonic muscular dystrophy type 1; RA, Rheumatoid Arthritis.
3.3. Quality assessment
Evaluating the general risk of bias mentioned 111 studies with a low risk of bias [32,33,36,38–40,42–46,48,49,51–57,60–62,64–66,68,69,72–74,76,77,79–81,84–86,90–94,96–109,111–120,122–129,131,132,134–140,142–145,147–150,152–155,158–163,165–168,170–173], 17 studies with a high risk of bias [34,37,41,47,58,70,71,78,82,87,88,121,141,151,156,157,169], and the others indicated an unclear risk of bias [9,35,50,59,63,67,75,83,89,95,110,130,133,146,164] (Table 2).
Table 2.
Study | Random sequence generation | Allocation concealment | Selective reporting | Other sources of bias | Blinding (participants and personnel) | Blinding (outcome assessment) | Incomplete outcome data | General risk of bias |
---|---|---|---|---|---|---|---|---|
Balsom et al. 1993 | H | H | L | H | L | U | L | Fair |
Mujika et al. 1996 | U | U | L | L | L | H | L | Good |
Terrillion et al. 1997 | H | H | L | L | H | H | L | Weak |
Vanderberghe et al. 1997 | H | H | L | L | L | H | L | Weak |
Noonan et al. 1998a | U | U | L | L | L | H | L | Good |
Noonan et al. 1998b | U | U | L | L | L | H | L | Good |
Kreider et al. 1998 | U | U | L | L | L | H | U | Good |
Oopik et al. 1998 | H | H | L | L | H | H | L | Weak |
Maganaris et al. 1998 | U | U | L | L | L | H | L | Good |
Bermon et al. 1998a | U | U | L | L | L | U | L | Good |
Bermon et al. 1998b | U | U | L | L | L | U | L | Good |
Vukovich et al. 1998a | U | U | L | L | L | H | L | Good |
Vukovich et al. 1998b | U | U | L | L | L | H | L | Good |
Kelly et al. 1998 | U | U | L | L | H | H | H | Weak |
Mckenna et al. 1999 | U | U | L | L | L | H | L | Good |
Francaux et al. 1999 | U | U | L | U | L | U | L | Good |
Rawson et al. 1999 | U | U | L | L | L | H | L | Good |
Pearson et al. 1999 | U | U | U | L | L | H | L | Good |
Leenders et al. 1999a | U | U | L | L | L | H | L | Good |
Leenders et al. 1999b | U | U | L | L | L | H | L | Good |
Peeters et al. 1999a | H | H | L | L | L | H | L | Weak |
Peeters et al. 1999b | H | H | L | L | L | H | L | Weak |
Haff et al. 2000 | U | U | L | L | L | U | L | Good |
Schedel et al. 2000 | U | U | L | L | L | H | L | Good |
Deutekom et al. 2000 | U | U | H | L | L | H | L | Fair |
Mihic et al. 2000 | U | U | L | L | L | H | L | Good |
Hamilton et al. 2000 | U | U | L | L | L | U | L | Good |
Larson-Meyer et al. 2000 | U | U | L | L | L | H | L | Good |
Volek et al. 2000 | U | U | L | L | L | H | L | Good |
Becque et al. 2000 | H | L | L | U | L | U | L | Good |
Brenner et al. 2000 | U | U | L | L | L | U | L | Good |
Skare et al. 2001 | H | H | L | H | H | H | L | Weak |
Green et al. 2001 | U | U | L | U | L | U | H | Good |
Rockwell et al. 2001 | U | U | L | L | L | H | U | Good |
Op t Eijnde et al. 2001 | U | U | L | L | L | H | L | Good |
Bemben et al. 2001 | U | U | L | L | L | U | L | Good |
Chrusch et al. 2001 | U | U | L | L | L | U | L | Good |
Kern et al. 2001 | U | U | L | L | L | H | L | Good |
Parise et al. 2001a | U | U | H | L | L | H | L | Fair |
Parise et al. 2001b | U | U | H | L | L | H | L | Fair |
Wilder et al. 2001a | U | U | L | L | H | H | L | Fair |
Wilder et al. 2001b | U | U | L | L | H | H | L | Fair |
Willoughby et al. 2001 | U | U | L | L | L | H | L | Good |
Hespel et al. 2001 | U | U | L | U | L | U | L | Good |
Coxe et al. 2002 | H | U | H | L | L | H | L | Weak |
Gotshalk et al. 2002 | U | U | L | U | L | U | L | Good |
Kilduff et al. 2002 | H | H | L | L | L | H | L | Weak |
Wilder et al. 2002a | U | U | L | L | H | H | U | Fair |
Wilder et al. 2002b | U | U | L | L | H | H | U | Fair |
Walter et al. 2002 | U | U | L | L | L | H | L | Good |
Huso et al. 2002 | U | U | L | L | L | U | L | Good |
Warber et al. 2002 | U | U | L | L | L | H | L | Good |
Kutz et al. 2003 | H | H | L | L | L | H | L | Weak |
Vukovich et al. 2003 | H | H | L | H | H | H | H | Weak |
Lehmkuhl et al. 2003 | U | U | L | L | L | H | L | Good |
Burke et al. 2003a | L | L | L | L | L | U | L | Good |
Burke et al. 2003b | L | L | L | L | L | U | L | Good |
Van Loon et al. 2003 | H | H | L | L | L | H | L | Weak |
Zajac et al. 2003 | U | U | L | H | L | H | L | Fair |
Eijnde et al. 2003a | U | U | L | U | L | U | L | Good |
Eijnde et al. 2003b | U | U | L | U | L | U | L | Good |
Kambis et al. 2003 | U | U | L | L | L | U | L | Good |
Brose et al. 2003 a | U | U | L | L | L | U | L | Good |
Brose et al. 2003 b | U | U | L | L | L | U | L | Good |
Watsford et al. 2003 | U | U | L | L | L | H | U | Good |
Eckerson et al. 2004 | U | U | L | U | L | L | L | Good |
Kinugasa et al. 2004 | H | H | L | L | L | H | L | Weak |
Javierre et al. 2004 | U | U | L | U | H | H | L | Fair |
Volek et al. 2004 | U | U | L | L | L | H | L | Good |
Ball SD et al. 2004 | U | U | L | L | L | U | L | Good |
Tarnopolosky et al. 2004 | L | L | L | L | L | H | L | Good |
Taes et al. 2004 | U | U | L | L | L | H | L | Good |
Anomasiri et al. 2004 | U | U | L | U | L | U | L | Good |
Eckerson et al. 2005a | U | U | L | U | L | U | L | Good |
Eckerson et al. 2005b | U | U | L | U | L | U | L | Good |
Eckerson et al. 2005c | U | U | L | U | L | U | L | Good |
Eckerson et al. 2005d | U | U | L | U | L | U | L | Good |
Perret et al. 2005 | U | H | L | L | L | H | L | Fair |
Ahmun et al. 2005 | U | U | L | L | L | U | L | Good |
Mendell et al. 2005 | H | H | L | H | L | H | L | Weak |
Fuld et al. 2005 | U | U | L | U | L | U | L | Good |
Hoffman et al. 2005 | U | U | H | L | L | H | L | Fair |
Kuethe et al. 2006 | H | U | L | U | L | U | L | Good |
Hille et al. 2006 | U | U | L | U | L | U | L | Good |
Norman et al. 2006 | L | L | L | L | L | H | L | Good |
Ferguson et al. 2006 | U | U | L | L | L | U | L | Good |
Pluim et al. 2006 | U | U | H | L | L | H | H | Weak |
Rogers et al. 2006 | U | U | L | L | L | H | L | Good |
Hoffman et al. 2006 | U | U | L | L | L | U | L | Good |
Smith et al. 2007 | U | U | H | L | L | H | L | Fair |
Stout et al. 2007 | U | U | L | L | L | H | L | Good |
Silva et al. 2007 | U | U | L | L | L | H | L | Good |
Wright et al. 2007 | H | H | L | H | H | H | L | Weak |
De Souza junior et al. 2007 | U | U | L | U | L | U | L | Good |
Cribb et al. 2007 a | U | U | L | L | L | U | L | Good |
Cribb et al. 2007 b | U | U | L | L | L | U | L | Good |
Hass et al. 2007 | U | U | L | L | L | H | L | Good |
Chilibeck et al. 2007 | U | U | L | L | L | U | L | Good |
Cribb et al. 2007 | U | U | L | L | L | U | L | Good |
Walter et al. 2008 | U | U | L | L | L | H | L | Good |
Eckerson et al. 2008 | U | U | L | U | L | U | L | Good |
Gotshalk et al. 2008 | U | U | L | L | L | H | L | Good |
Deacon et al. 2008 | L | L | L | L | L | L | H | Good |
Eliot et al. 2008 a | U | U | L | L | L | U | L | Good |
Eliot et al. 2008 b | U | U | L | L | L | U | L | Good |
Little et al. 2008 | U | U | L | L | L | H | L | Good |
Jager et al. 2008 a | U | U | L | L | L | H | L | Good |
Jager et al. 2008 b | U | U | L | L | L | H | L | Good |
Sakkas et al. 2009 | L | L | L | L | L | H | U | Good |
Bazzucchi et al. 2009 | U | H | L | U | L | U | H | Fair |
Spillane et al.2009a | U | U | L | L | L | H | L | Good |
Spillane et al. 200 b | U | U | L | L | L | H | L | Good |
Herda et al. 2009a | U | U | L | U | L | U | L | Good |
Herda et al. 2009b | U | U | L | U | L | U | L | Good |
Herda et al. 2009c | U | U | L | U | L | U | L | Good |
Fukuda et al. 2010a | U | U | L | U | L | U | L | Good |
Fukuda et al. 2010b | U | U | L | U | L | U | L | Good |
Hickner et al. 2010 | H | U | L | L | L | H | L | Fair |
Saremi et al. 2010 | L | L | L | L | L | H | U | Good |
Camic et al. 2010 | U | U | L | L | L | U | L | Good |
Smith et al. 2011a | U | U | L | L | L | H | L | Good |
Smith et al. 2011b | U | U | L | L | L | H | L | Good |
Neves JR et al. 2011 | L | L | L | L | L | H | L | Good |
Rawson et al. 2011 | L | U | L | L | L | H | L | Good |
Taylor et al. 2011 | U | U | L | L | L | H | L | Good |
Mohebbi et al. 2012 | H | H | L | L | L | H | L | Weak |
Zuniga et al. 2012 | U | U | L | L | L | H | L | Good |
Pericario et al. 2012 | U | U | L | L | L | H | U | Good |
Sterkowicz et al. 2012 | U | U | L | L | L | H | L | Good |
Montes De Oca et al. 2013 | U | U | L | L | L | U | L | Good |
Aguiar et al. 2013 | U | L | L | L | L | U | L | Good |
Cooke et al. 2014 | U | U | L | L | L | H | L | Good |
Gualano et al. 2014a | L | L | L | L | L | U | L | Good |
Gualano et al. 2014b | L | L | L | L | L | U | L | Good |
Kresta et al. 2014(a) | U | U | L | L | L | H | U | Good |
kresta et al. 2014(b) | U | U | L | L | L | H | U | Good |
Hayashi et al. 2014 | U | L | L | L | L | U | L | Good |
Nemezio et al. 2015 | U | L | L | L | L | U | L | Good |
Aedma et al. 2015 | H | U | L | L | L | U | L | Good |
Lobo et al. 2015 | L | U | L | L | L | H | L | Good |
Candow et al. 2015a | U | L | L | L | L | U | L | Good |
Candow et al. 2015b | U | L | L | L | L | U | L | Good |
Chilibeck et al. 2015 | L | L | H | L | L | L | H | Fair |
Deminice et al. 2015 | U | U | L | L | L | U | L | Good |
Wilkinson et al. 2016 | L | L | L | L | L | H | H | Fair |
Forbes et al. 2016 | L | L | L | L | L | U | L | Good |
Pinto et al. 2016 | L | U | L | L | L | H | L | Good |
Collins et al. 2016 | U | L | L | L | L | H | L | Good |
Johannsmeyer et al. 2016 | L | L | L | L | L | H | L | Good |
Backx et al. 2017 | U | U | L | L | L | U | L | Good |
Wilborn et al. 2017 | U | U | L | L | L | H | L | Good |
Karamat et al. 2017 | L | L | L | H | L | L | L | Good |
Atakan et al. 2018 | L | U | L | U | L | U | L | Good |
Wang et al. 2018 | U | U | L | L | L | H | L | Good |
Vanbavel et al. 2019 | U | U | L | L | H | H | H | Weak |
Arazi et al. 2019 | U | U | H | U | L | U | L | Good |
Almeida et al. 2020 | U | U | L | U | L | U | L | Good |
Marini et al. 2020 | U | H | L | L | L | H | L | Fair |
Candow et al. 2020 | L | L | L | L | L | L | L | Good |
Delextrat et al. 2020a | U | U | L | L | L | U | L | Good |
Delextrat et al. 2021b | U | U | L | L | L | U | L | Good |
Anders et al. 2021 | U | U | L | L | L | U | L | Good |
Pakulak et al. 2021a | U | U | L | L | L | H | U | Good |
pakulak et al. 2021b | U | U | L | L | L | H | U | Good |
Bonilla et al. 2021 | L | U | L | L | H | U | L | Good |
Butchart et al. 2022 | U | U | L | L | L | U | L | Good |
Almeida et al. 2022 | U | U | L | U | L | U | L | Good |
Dinan et al. 2022a | L | L | L | L | L | U | L | Good |
Dinan et al. 2022b | L | L | L | L | L | U | L | Good |
Askow et al. 2022 | U | L | L | L | L | U | L | Good |
Moore et al. 2023a | L | L | L | L | L | U | L | Good |
Moore et al. 2023b | L | L | L | L | L | U | L | Good |
Note: L; low risk of bias; H, high risk of bias; U, unclear risk of bias.
General Low risk<2 high risk.
General moderate risk=2 high risk.
General high risk>2 high risk.
4. Meta-analysis
4.1. Effect of creatine supplementation on body composition in adults
4.1.1. Effect of creatine supplementation on body mass and body mass index
Analyzing 154 overall effect sizes demonstrated a significant increase in body mass following creatine supplementation (WMD: 0.86kg; 95% CI: 0.76 to 0.96; p<0.001) (Figure 2A). However, no degree of heterogeneity was found (I2=0.0%). Evaluating the results of subgroup analysis showed that the effect of creatine supplementation on body mass was independent of age, sex, activity status of participants, trial duration, intervention dose, loading protocol, type of creatine, and type of training program during the intervention (Table 3). Overall, results from the random effects model indicated that creatine supplementation failed to change body mass index (WMD: 0.20kg/m2; 95% CI: −0.17 to 0.58; p=0.299) (Figure 2B). Moreover, no degree of between-studies heterogeneity was observed (I2=0.0%) (Table 3).
Table 3.
Number of effect sizes | WMD (95%CI) | P-value | heterogeneity | |||
---|---|---|---|---|---|---|
P heterogeneity | I2 | P between sub-groups | ||||
Subgroup analyses of creatine on body mass (kg) | ||||||
Overall effect | 154 | 0.86 (0.76, 0.96) | <0.001 | 1.000 | 0.0% | |
Trial duration (d) | ||||||
≤30 | 89 | 0.87 (0.77, 0.98) | <0.001 | 1.000 | 0.0% | 0.490 |
>30 | 65 | 0.76 (0.47, 1.06) | <0.001 | 1.000 | 0.0% | |
Intervention dose (g/d) | ||||||
≤5 | 68 | 0.91 (0.78, 1.04) | <0.001 | 1.000 | 0.0% | 0.256 |
>5 | 86 | 0.80 (0.65, 0.94) | <0.001 | 1.000 | 0.0% | |
Baseline BMI (kg/m2) | ||||||
Normal (18.5–24.9) | 15 | 0.81 (0.11, 1.51) | 0.022 | 1.000 | 0.0% | 0.523 |
Overweight (25–29.9) | 9 | 0.48 (−0.24, 1.22) | 0.195 | 0.998 | 0.0% | |
Sex | ||||||
Male | 93 | 0.89 (0.78, 1.01) | <0.001 | 1.000 | 0.0% | |
Both | 33 | 0.57 (0.24, 0.91) | 0.001 | 1.000 | 0.0% | |
Female | 27 | 0.86 (0.62, 1.09) | <0.001 | 0.824 | 0.0% | |
Participant’s age | ||||||
<40 | 75 | 0.93 (0.82, 1.04) | <0.001 | 1.000 | 0.0% | 0.077 |
>40 | 29 | 0.60 (0.7825 0.95) | 0.001 | 1.000 | 0.0% | |
Activity status | ||||||
Trained | 58 | 0.94 (0.76, 1.12) | <0.001 | <0.001 | 0.0% | 0.179 |
Active | 45 | 0.86 (0.74, 0.99) | <0.001 | 0.994 | 0.0% | |
Non-active | 51 | 0.60 (0.28, 0.91) | <0.001 | <0.001 | 0.0% | |
Along with exercise | ||||||
AT | 17 | 0.95 (0.58, 1.32) | <0.001 | 0.993 | 0.0% | 0.068 |
CT | 40 | 0.59 (0.31, 0.88) | <0.001 | 0.997 | 0.0% | |
No exercise | 17 | 0.50 (0.08, 0.92) | 0.018 | 0.992 | 0.0% | |
RT | 57 | 0.89 (0.76, 1.01) | <0.001 | 1.000 | 0.0% | |
Loading | ||||||
Just loading | 48 | 0.54 (−0.14, 1.23) | <0.001 | 0.998 | 0.0% | 0.685 |
Loading+short maintenance | 22 | 0.91 (0.78, 1.05) | <0.001 | 1.000 | 0.0% | |
Maintenance | 43 | 0.98 (0.60, 1.36) | <0.001 | 1.000 | 0.0% | |
High dose maintenance | 6 | 1.26 (0.03, 2.48) | 0.036 | 0.997 | 0.0% | |
loading+long maintenance | 32 | 0.66 (0.26, 1.07) | 0.002 | 0.975 | 0.0% | |
Type of creatine | ||||||
CrC | 12 | 0.89 (0.65, 1.13) | <0.001 | 0.423 | 2.2% | 0.971 |
CM | 128 | 0.85 (0.74, 0.96) | <0.001 | 1.000 | 0.0% | |
Other | 5 | 0.98 (−0.00, 1.98) | 0.052 | 0.261 | 20.4% | |
Subgroup analyses of creatine on BMI (kg/m2) | ||||||
Overall effect | 13 | 0.20 (−0.17, 0.58) | 0.299 | 1.000 | 0.0% | |
Trial duration (d) | ||||||
≤30 | 5 | 0.31 (−0.22, 0.84) | 0.254 | 0.996 | 0.0% | 0.568 |
>30 | 8 | 0.08 (−0.45, 0.63) | 0.749 | 0.999 | 0.0% | |
Intervention dose (g/d) | ||||||
≤5 | 12 | 0.18 (−0.21, 0.59) | 0.364 | 1.000 | 0.0% | 0.850 |
>5 | 1 | 0.30 (−0.78, 1.38) | 0.589 | - | - | |
Baseline BMI (kg/m2) | ||||||
Normal (18.5–24.9) | 6 | 0.25 (−0.27, 0.79) | 0.344 | 0.977 | 0.0% | 0.779 |
Overweight (25–29.9) | 5 | 0.14 (−0.41, 0.71) | 0.610 | 0.992 | 0.0% | |
Sex | ||||||
Male | 3 | 0.41 (−0.31, 1.14) | 0.267 | 0.962 | 0.0% | 0.769 |
Both | 8 | 0.08 (−0.45, 0.61) | 0.768 | 0.999 | 0.0% | |
Female | 2 | 0.22 (−0.58, 1.02) | 0.593 | 0.923 | 0.0% | |
Participant’s age | ||||||
<40 | 4 | 0.28 (−0.31, 0.88) | 0.352 | 0.995 | 0.0% | 0.585 |
>40 | 6 | 0.05 (−0.51, 0.62) | 0.849 | 0.993 | 0.0% | |
Activity status | ||||||
Active | 1 | 0.30 (−0.81, 1.41) | 0.597 | - | - | 0.945 |
Trained | 4 | 0.29 (−0.56, 1.16) | 0.499 | 0.993 | 0.0% | |
Non-active | 8 | 0.15 (−0.29, 0.61) | 0.499 | 0.995 | 0.0% | |
Along with exercise | ||||||
CT | 1 | 0.53 (−1.61, 2.67) | 0.628 | - | - | 0.990 |
No exercise | 3 | 0.16 (−0.58, 0.91) | 0.663 | 0.992 | 0.0% | |
AT | 1 | 0.30 (−0.78, 1.38) | 0.589 | - | - | |
RT | 5 | 0.08 (−0.60, 0.76) | 0.819 | 0.989 | 0.0% | |
Loading | ||||||
Just loading | 1 | 0.30 (−0.78, 1.38) | 0.589 | - | - | 0.932 |
Loading+short maintenance | 1 | 0.08 (−2.27, 2.43) | 0.947 | - | - | |
Maintenance | 6 | 0.23 (−0.30, 0.77) | 0.390 | 1.000 | 0.0% | |
loading+long maintenance | 4 | −0.05 (−0.82, 0.71) | 0.893 | 0.962 | 0.0% | |
Type of creatine | ||||||
CM | 11 | 0.14 (−0.26, 0.56) | 0.481 | 1.000 | 0.0% | 0.805 |
Other | 1 | 0.53 (−1.61, 2.67) | 0.376 | - | - | |
Subgroup analyses of creatine on FM (kg) | ||||||
Overall effect | 62 | 0.05 (−0.24, 0.35) | 0.703 | 1.000 | 0.0% | |
Trial duration (d) | ||||||
≤30 | 15 | 0.34 (−0.21, 0.89) | 0.227 | 0.921 | 0.0% | 0.233 |
>30 | 47 | −0.06 (−0.41, 0.29) | 0.742 | 1.000 | 0.0% | |
Intervention dose (g/d) | ||||||
≤5 | 35 | 0.25 (−0.16, 0.67) | 0.231 | 0.999 | 0.0% | 0.183 |
>5 | 27 | −0.15 (−0.58, 0.27) | 0.487 | 0.992 | 0.0% | |
Baseline BMI (kg/m2) | ||||||
Normal (18.5–24.9) | 8 | −0.25 (−0.78, 0.27) | 0.349 | 0.917 | 0.0% | 0.287 |
Overweight (25–29.9) | 10 | 0.29 (−0.47, 1.05) | 0.457 | 0.975 | 0.0% | |
Obese (≥30) | 1 | −3.60 (−9.91, 2.71) | 0.264 | - | - | |
Sex | ||||||
Male | 30 | 0.28 (−0.13, 0.69) | 0.185 | 0.991 | 0.0% | 0.494 |
Both | 21 | −0.14 (−0.64, 0.34) | 0.556 | 0.988 | 0.0% | |
Female | 10 | −0.29 (−1.16, 0.58) | 0.515 | 0.977 | 0.0% | |
Participant’s age | ||||||
<40 | 30 | −0.12 (−0.63, 0.38) | 0.619 | 1.000 | 0.0% | 0.775 |
>40 | 21 | −0.02 (−0.51, 0.46) | 0.917 | 0.920 | 0.0% | |
Activity status | ||||||
Active | 15 | 0.01 (−0.59, 0.62) | 0.966 | 0.746 | 0.0% | 0.891 |
Trained | 18 | 0.17 (−0.38, 0.73) | 0.542 | 1.000 | 0.0% | |
Non-active | 29 | 0.01 (−0.42, 0.44) | 0.959 | 0.992 | 0.0% | |
Along with exercise | ||||||
CT | 11 | −0.14 (−0.81, 0.52) | 0.667 | 0.765 | 0.0% | 0.927 |
No exercise | 5 | 0.26 (−0.58 1.10) | 0.546 | 0.991 | 0.0% | |
AT | 2 | −0.09 (−1.14, 0.95) | 0.864 | 0.590 | 0.0% | |
RT | 40 | 0.09 (−0.30, 0.48) | 0.658 | 0.998 | 0.0% | |
Loading | ||||||
Just loading | 5 | 0.15 (−0.77, 1.08) | 0.746 | 0.992 | 0.0% | 0.859 |
Loading+short maintenance | 7 | 0.51 (−0.55, 1.58) | 0.345 | 0.356 | 9.6% | |
Maintenance | 28 | −0.08 (−0.60, 0.44) | 0.764 | 0.998 | 0.0% | |
High dose maintenance | 2 | 0.28 (−0.70, 1.28) | 0.573 | 0.698 | 0.0% | |
loading+long maintenance | 20 | −0.02 (−0.50, 0.46) | 0.927 | 0.983 | 0.0% | |
Type of creatine | ||||||
CM | 59 | 0.05 (−0.24, 0.35) | 0.723 | 1.000 | 0.0% | 0.934 |
Other | 2 | 0.01 (−2.01, 2.04) | 0.693 | - | - | |
Subgroup analyses of creatine on BFP (%) | ||||||
Overall effect | 89 | −0.28 (−0.47, −0.09) | 0.004 | 0.968 | 0.0% | |
Trial duration (d) | ||||||
≤30 | 36 | −0.30 (−0.65, 0.04) | 0.084 | 0.341 | 7.5% | 0.512 |
>30 | 53 | −0.16 (−0.41, 0.08) | 0.200 | 0.999 | 0.0% | |
Intervention dose (g/d) | ||||||
≤5 | 51 | −0.04 (−0.29, 0.20) | 0.734 | 0.986 | 0.0% | 0.005 |
>5 | 38 | −0.60 (−0.89, −0.30) | <0.001 | 0.903 | 0.0% | |
Baseline BMI (kg/m2) | ||||||
Normal (18.5–24.9) | 7 | −0.26 (−0.74, 0.21) | 0.279 | 0.995 | 0.0% | 0.549 |
Overweight (25–29.9) | 8 | −0.08 (−0.44, 0.28) | 0.668 | 0.712 | 0.0% | |
Sex | ||||||
Male | 55 | −0.36 (−0.61, −0.11) | 0.005 | 0.593 | 0.0% | 0.622 |
Both | 18 | −0.15 (−0.68, 0.37) | 0.558 | 0.996 | 0.0% | |
Female | 16 | −0.18 (−0.52, 0.16) | 0.299 | 0.934 | 0.0% | |
Participant’s age | ||||||
<40 | 45 | −0.19 (−0.52, 0.13) | 0.244 | 0.998 | 0.0% | 0.779 |
>40 | 20 | −0.13 (−0.44, 0.17) | 0.401 | 0.998 | 0.0% | |
Activity status | ||||||
Active | 18 | −0.04 (−0.80, 0.73) | 0.920 | 0.067 | 35.7% | 0.063 |
Trained | 37 | −0.56 (−0.86, −0.26) | <0.001 | 0.968 | 0.0% | |
Non-active | 34 | −0.10 (−0.37, 0.17) | 0.474 | 1.000 | 0.0% | |
Along with exercise | ||||||
CT | 22 | −0.83 (−1.22, −0.44) | <0.001 | 0.741 | 0.0% | 0.022 |
No exercise | 7 | −0.32 (−0.82, 0.17) | 0.202 | 0.724 | 0.0% | |
AT | 6 | −0.37 (−1.14, 0.39) | 0.341 | 0.903 | 0.0% | |
RT | 43 | −0.02 (−0.30, 0.25) | 0.864 | 0.911 | 0.0% | |
Loading | ||||||
Just loading | 12 | −0.10 (−0.61, 0.41) | 0.699 | 1.000 | 0.0% | 0.177 |
Loading+short maintenance | 15 | 0.14 (−0.63, 0.93) | 0.711 | 0.288 | 14.8% | |
Maintenance | 32 | −0.59 (−0.91, −0.28) | <0.001 | 0.527 | 0.0% | |
High dose maintenance | 5 | −0.17 (−1.03, 0.69) | 0.698 | 0.763 | 0.0% | |
loading+long maintenance | 25 | −0.14 (−0.45, 0.16) | 0.363 | 0.996 | 0.0% | |
Type of creatine | ||||||
CrC | 1 | −0.10 (−3.42, 3.22) | 0.953 | - | - | 0.720 |
CM | 80 | −0.31 (−0.51, −0.11) | 0.002 | 0.921 | 0.0% | |
Other | 4 | 0.21 (−0.85, 1.28) | 0.693 | 0.781 | 0.0% | |
Subgroup analyses of creatine on FFM (kg) | ||||||
Overall effect | 95 | 0.82 (0.57, 1.06) | <0.001 | 1.000 | 0.0% | |
Trial duration (d) | ||||||
≤30 | 31 | 1.07 (0.48, 1.66) | <0.001 | 0.996 | 0.0% | 0.357 |
>30 | 64 | 0.76 (0.49, 1.03) | <0.001 | 1.000 | 0.0% | |
Intervention dose (g/d) | ||||||
≤5 | 52 | 0.77 (0.46, 1.08) | <0.001 | 1.000 | 0.0% | 0.663 |
>5 | 43 | 0.89 (0.49, 1.29) | <0.001 | 0.981 | 0.0% | |
Baseline BMI (kg/m2) | ||||||
Normal (18.5–24.9) | 7 | 1.12 (0.59, 1.65) | <0.001 | 0.829 | 0.0% | 0.270 |
Overweight (25–29.9) | 8 | 0.39 (−0.34, 1.13) | 0.293 | 0.905 | 0.0% | |
Obese (≥30) | 1 | −0.40 (−6.69, 5.89) | 0.901 | - | - | |
Sex | ||||||
Male | 51 | 1.20 (0.80, 1.60) | <0.001 | 1.000 | 0.0% | 0.120 |
Both | 25 | 0.60 (0.21, 0.99) | 0.002 | 0.970 | 0.0% | |
Female | 18 | 0.54 (0.03, 1.06) | 0.036 | 1.000 | 0.0% | |
Participant’s age | ||||||
<40 | 48 | 0.89 (0.45, 1.33) | <0.001 | 1.000 | 0.0% | 0.955 |
>40 | 27 | 0.87 (0.53, 1.22) | <0.001 | 0.996 | 0.0% | |
Activity status | ||||||
Active | 26 | 0.71 (0.01, 1.41) | 0.045 | 1.000 | 0.0% | 0.194 |
Trained | 32 | 1.31 (0.72, 1.90) | <0.001 | 0.999 | 0.0% | |
Non-active | 37 | 0.71 (0.42, 1.01) | <0.001 | 0.994 | 0.0% | |
Along with exercise | ||||||
CT | 26 | 1.00 (0.48, 1.52) | <0.001 | 0.934 | 0.0% | 0.143 |
No exercise | 7 | 0.24 (−0.26, 0.75) | 0.347 | 0.854 | 0.0% | |
AT | 6 | 1.19 (−0.09, 2.48) | 0.068 | 0.989 | 0.0% | |
RT | 48 | 0.99 (0.64, 1.35) | <0.001 | 1.000 | 0.0% | |
Loading | ||||||
Just loading | 10 | 0.88 (−0.36, 2.13) | 0.165 | 1.000 | 0.0% | 0.828 |
Loading+short maintenance | 19 | 0.52 (−0.24, 1.29) | 0.179 | 0.999 | 0.0% | |
Maintenance | 32 | 0.72 (0.32, 1.12) | <0.001 | 0.912 | 0.0% | |
High dose maintenance | 3 | 1.34 (−0.40, 3.09) | 0.131 | 0.976 | 0.0% | |
loading+long maintenance | 31 | 0.93 (0.57, 1.29) | <0.001 | 0.996 | 0.0% | |
Type of creatine | ||||||
CM | 89 | 0.82 (0.57, 1.06) | <0.001 | 1.000 | 0.0% | 0.997 |
Other | 3 | 0.91 (−3.06, 4.88) | 0.653 | 0.834 | 0.0% |
Note: Abbreviations: WMD, weighted mean differences; CI, confidence interval; BMI, body mass index.
4.1.2. Effect of creatine supplementation on fat-free mass
Combined results from 95 effect sizes indicated a small, yet significant increase in fat-free mass following creatine supplementation (WMD: 0.82kg; 95% CI: 0.57 to 1.06; p<0.001) (Figure 2E). Additionally, we observed no degree of between-studies heterogeneity (I2=0.0%). Subgroup analysis revealed that creatine supplementation increased fat-free mass in studies that used combined or resistance training interventions or creatine monohydrate as a supplement. Moreover, using a maintenance dose, or creatine loading with a long maintenance dose had significant effects on fat-free mass. Descriptively, the results appeared to be greater among males (Table 3).
4.1.3. Effect of creatine supplementation on fat mass and body fat percentage
Pooled data from 62 effect sizes demonstrated no significant effect of creatine supplementation on fat mass (WMD: 0.05kg; 95% CI: −0.24 to 0.35; p=0.703) (Figure 2C), with no observed heterogeneity among the studies (I2=0.0%) (Table 3). Subgroup analysis failed to show any significant change in the results. According to the results from 89 effect sizes, creatine supplementation resulted in a very small reduction in body fat percentage (WMD: −0.28 %; 95% CI: −0.47 to−0.09; p=0.004) (Figure 2D). There was no heterogeneity among studies (I2=0.0%). Subgroup analysis revealed a significant reduction in body fat percentage in studies with supplementation dosages of more than 5g/day, trained participants, and studies that used a combination of creatine supplementation with combined training. Also, studies that used creatine supplementation protocol with a maintenance dose or creatine monohydrate showed a significant reduction in body fat percentage (Table 3).
4.2. Sensitivity analysis
To ascertain the impact of each study on the overall effect size, each trial was excluded from the analysis step by step. Assessing the results of the sensitivity analysis indicated no significant alteration in the total effect of creatine supplementation on body mass, body mass index, fat-free mass, fat mass, and body fat percentage (Table 4).
Table 4.
Publication bias | | |
---|---|---|
Outcomes | Egger’s test | Sensitivity |
Body weight | 0.440 | None |
BMI | 0.533 | None |
FM | 0.350 | None |
BFP | 0.212 | None |
FFM | 0.169 | None |
4.3. Publication bias
The overall results of Egger’s regression test and inspecting the funnel plots provided no evidence of publication bias (Table 4) (Figure 3).
4.4. Non-linear dose-response analysis
The results of the dose-response analysis indicated a significant association between creatine doses with changes in fat mass (p=0.039; Table 5 and Figure 4C) and fat-free mass (p=0.008; Table 5 and Figure 4E). Also, a significant association between the duration of creatine supplementation and changes in body mass (p=0.030; Table 5 and Figure 5A) was observed.
Table 5.
Regression | Dose-response | |||||||
---|---|---|---|---|---|---|---|---|
Dose (mg/d) | Duration (week) | Dose (mg/d) | Duration (week) | |||||
Variables | Coefficient | p-value | Coefficient | p-value | Coefficient | p-value | Coefficient | p-value |
Body Mass | −0.46 | 0.505 | −1.38 | 0.770 | −0.06 | 0.392 | −0.56 | 0.030 |
BMI | 4.48 | 0.507 | −25.70 | 0.835 | −0.07 | 0.194 | −0.27 | 0.128 |
FM | −0.33 | 0.578 | −10.24 | 0.177 | −2.02 | 0.039 | −0.65 | 0.074 |
BFP | −0.71 | 0.353 | 1.59 | 0.806 | −3.45 | 0.063 | −0.56 | 0.210 |
FFM | 0.91 | 0.144 | −1.74 | 0.810 | 1.75 | 0.008 | 0.13 | 0.454 |
4.5. Meta-regression analysis
The results of the meta-regression test showed that there was no significant association between the dosage and duration of creatine supplementation and alterations in body composition variables (Table 5, Figures 6,7).
4.6. GRADE analysis
The quality of evidence was assessed using the GRADE protocol in this meta-analysis. The quality of evidence in studies evaluating the creatine supplementation impact on body mass index and fat mass is regarded as moderate. Moreover, the evidence quality in studies aimed to estimate the influence of creatine supplementation on body mass, fat-free mass, and body fat percentage was upgraded to high (Table 6).
Table 6.
Outcomes | Risk of bias | Inconsistency | Indirectness | Imprecision | Publication Bias | Quality of evidence |
---|---|---|---|---|---|---|
Body weight | No serious limitation | No serious limitation | No serious limitation | No serious limitation | No serious limitation | High |
BMI | No serious limitation | No serious limitation | No serious limitation | Serious limitation2 | No serious limitation | Moderate |
FM | No serious limitation | No serious limitation | No serious limitation | Serious limitation2 | No serious limitation | Moderate |
BFP | No serious limitation | No serious limitation | No serious limitation | No serious limitation | No serious limitation | High |
FFM | No serious limitation | No serious limitation | No serious limitation | No serious limitation | No serious limitation | High |
1- There is no evidence of significant effects of creatine supplementation on BMI and FM..
4.7. Discussion
Overall, the most important outcomes from this comprehensive systematic review and meta-analysis were that creatine supplementation results in a small favorable effect on measures of fat-free mass and body fat percentage over time. Sub-analyses revealed that fat-free mass was significantly increased when (1) creatine was ingested in conjunction with either combined concurrent (aerobic+resistance training) training or resistance training alone, (2) creatine monohydrate was used, and (3) a maintenance dose (with or without a loading phase) was implemented. Moreover, it was shown that research including a daily creatine intake of more than 5g or studies combining aerobic and resistance training in their experimental design exhibited a significant reduction in body fat percentage. No significant differences were found in any of the variables when subgrouping was done based on sex. However, it was observed that men exhibited a 1.20kg increase in fat-free mass, while females had a smaller rise of 0.54kg. Age, training status, and study duration did not appear to influence any of the outcome variables.
5. Loading protocol of creatine supplementation and training intervention
5.1. Creatine and fat-free Mass
In support of several previous systematic reviews and meta-analyses [5,11,12,175–177], creatine supplementation significantly increased estimates of fat-free mass (overall) by 0.82kg (95% CI: 0.57, 1.06). This was only evident when creatine monohydrate was combined with resistance training or combination of resistance and aerobic training. Alternative forms of creatine (creatine malate, creatine ethyl ester and creatine phosphate) did appear to have a similar mean change in fat-free mass (Monohydrate: 0.82kg [95% CI: 0.57, 1.06]; Alternative forms: 0.91kg [−3.06, 4.88]). Few studies have examined the ergogenic effects of creatine-based compounds such as creatine malate, creatine ethyl ester and creatine phosphate, which limits the ability to draw strong conclusions. Sterkowicz et al. conducted a trial to determine the effects of 6-weeks of training with creatine malate supplementation on anaerobic capacity and aerobic power and in judo specific fitness performance. Results showed no effects of supplementation with creatine malate on body composition indices and physical performance compared to control [119]. In this study creatine malate was chosen due to its efficacy during absorption and digestion in the gastrointestinal tract. Another study examined the combined effects of creatine in the form of creatine ethyl ester and resistance training on body composition and muscle strength and power, when compared to creatine monohydrate, creatine ethyl ester failed to show significant improvements in body composition, muscle mass, and strength and power [111]. However, due to the limited number of studies, lack of statistical power, and large variability the alternative forms of creatine did not statistically increase fat-free mass compared to the placebo. Therefore, based on the current meta-analysis, creatine monohydrate is well-studied (n=89 RCTs), effective (p<0.001), has a well-developed safety profile [6], and is economical [15]. Additionally, confirmed by a previous review [178], creatine monohydrate is the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety recommended by professional societies and organizations. Future research may be warranted to explore alternative forms of creatine, however, presently it is clear that other forms of creatine are not superior to creatine monohydrate [15].
A prior meta-analysis included 22 RCTs with 721 older adults (age: 57–70years of age, both males and females) who demonstrated an increase in fat-free mass (~1.37kg, 95% CI: 0.97–1.76kg) when creatine was ingested during a resistance training program (training 2–3 times/week for 7 to 52weeks) compared to resistance training and placebo [5]. More recently, Delpino et al. (2022) included 35 studies with 1192 participants that revealed that creatine (with and without exercise) increased fat-free mass by 0.68kg (95% CI: 0.26–1.11), however, sub-analyses demonstrated that gains in fat-free mass only occurred when creatine was ingested with resistance training (1.10kg, 95% CI: 0.56–1.65) [12]. In contrast to the present investigation, the findings of Delpino et al. (2022) did not provide a statistically significant disparity in fat-free mass when creatine supplementation was administered in conjunction with a mixed regimen of aerobic and resistance training. In support of our findings, there was no significant effect on fat-free mass when creatine was ingested alone (without exercise). However, it is important to note that some of the observed increases in fat-free mass may be due to increases in body water retention (both extra- and intracellular). It is worth mentioning that several tools were used to measure body composition, such as bioelectric impedance analysis (BIA), BOD POD, hydrostatic weighting, hydro densitometry, skinfold equations, and dual-energy X-Ray absorptiometry. Among them, BIA is an electrical method which has the potential of quantifying total body water, extracellular water, intracellular water in addition to FM, FFM. However, due to the limited number of included studies that used BIA as body composition measurement tools (8 of 143 studies) or provided body water data, more studies are needed to confirm body water retention changes following creatine supplementation. A recent systematic review and meta-analysis involving 10 studies showed that the combination of creatine supplementation and resistance training increased regional measures of muscle accretion (0.10 to 0.16cm; as measured using ultrasound and peripheral quantitative computed tomography) compared to placebo [23]. Mechanistically, greater fat-free mass from creatine is likely related to its ability to increase high-energy phosphate, glycogen, calcium, and protein kinetics, stimulation of satellite cells and growth factors, or by decreasing inflammation and oxidative stress over time [2,179]. In theory, creatine will allow you to train at a higher training volume, which may enhance training adaptations over time (for a comprehensive review on mechanisms of creatine to enhance muscle see [5]).
5.2. Creatine and Body Fat
The overall pooled analysis in the current review revealed a very small, yet statistically significant decrease in body fat percentage following creatine supplementation (−0.28% [−0.47, −0.09]) compared to placebo. However, there were no significant changes in fat mass or body mass index. In theory, an increase in fat-free mass may increase energy expenditure and influence energy balance resulting in fat loss over time. In addition, in animal models there is evidence that a reduction in the availability of creatine in adipose tissue slows whole-body energy expenditure and increases fat accumulation [19,20]. Despite these potential mechanisms, based on the current review they do not appear to be sufficient to alter absolute fat mass in humans over time and support the notion that the change in body fat percentage is likely due to an increase in fat-free mass. Bonilla et al. provided 7.6g/day of creatine for 56days in young resistance-trained males. They found that creatine combined with resistance training increased fat-free mass and decreased body fat percentage over time [148]. Sub-analyses revealed that high-dose creatine (>5g/day), training status (i.e. being trained), exercise intervention, and the incorporation of a creatine maintenance dose following a creatine loading phase may influenced body fat percentage. In support of our findings, Forbes et al. (2019) observed a statistically significant decrease in body fat percentage when creatine was combined with resistance training [21] without a significant change in absolute fat mass. Nevertheless, there is ongoing debate over the potential efficacy of creatine supplementation in relation to decreasing body fat. Several research investigations have shown that there is no statistically significant difference in FM, BFP, or BMI after the administration of creatine supplements, regardless of whether exercise training is included or not [104,106,180–182]. The period of creatine supplementation in these studies was shorter than 30days, which may be considered inadequate for achieving changes in body composition. Additionally, workout program was not created with the intention of establishing a well-rounded routine to effectively observe the intended effects on FM.
5.3. Creatine and body Mass
The observed rise in body mass following creatine supplements may be associated with intramuscular fluid retention that occurs due to the osmotic characteristics of creatine [183]. Further, creatine supplementation combined with carbohydrates increases muscle glycogen storage, thereby further increasing water retention [184]. These small alterations in water-induced cell swelling increase myogenic regulatory factors and activate satellite cells involved in muscle hypertrophy [185]. Over time, the increase in body mass is likely due to a combination of water retention and an increase in lean tissue mass. In resistance-trained males (n=27) receiving either creatine or placebo over 8weeks had no changes in the ratio of skeletal muscle mass to intracellular water and only the creatine group had a decrease in the skeletal muscle mass to extracellular water ratio [186]. In females, there may be variations in water retention based on the phase of the menstrual cycle [173]. Thirty moderately active females were randomized to either creatine (20g/day for 5days) or placebo, with a menstrual phase crossover design. There were significant increases in total body water, extracellular fluid, and intracellular fluid in the creatine condition only during the luteal phase, while no condition differences were noted in the follicular phase. Despite these alterations in fluid retention, body mass was not different between conditions or across the menstrual cycle [173]. These findings appear to support our current meta-analysis which found no sex-related differences. Collectively, creatine supplementation appears to increase body mass compared to placebo by ~0.86kg.
In relation to the concept of loading protocol, it is worth noting that out of the total 154 research examined, a significant proportion of 48 studies did not include a maintenance phase subsequent to the loading phase. Interestingly, when comparing the collective impact of these studies that only focused on loading, it was shown that the effect on body mass was comparatively lower (0.54kg) than the studies that used maintenance doses of creatine as part of their supplementation protocol. In accordance with the findings of Rogers et al. a research study used a creatine supplementation regimen of 3g/d in conjunction with a strength training program spanning a duration of 12weeks. The findings indicated a significant increase of 2kg in body mass, which exhibited a notably greater magnitude in comparison to the control group receiving the placebo [187]. Similarly, Herda et al. conducted a study in which they administered a maintenance dosage of creatine supplementation (5g/d) without implementing any exercise program. The findings of this study demonstrated a notable augmentation in body mass after a 30-day period of creatine supplementation among the participants in the creatine group [188].
A further study conducted by Delextrat et al. yielded findings indicating that a 28-day period of creatine supplementation, without the first loading phase, among athletes involved in rocket sports resulted in a significant rise in body mass within the creatine group. Conversely, no such gain was seen within the placebo or beta-alanine groups [189]. Nevertheless, findings from a prior scoping study revealed that irrespective of varying doses of methods and exercises, favorable outcomes of creatine supplementation on muscular strength, muscle mass, and athletic performance were seen among young, healthy individuals [190]. In terms of training modality, 40 studies included a mix of AT and RT in their training regimen. Additionally, 17 studies exclusively utilized AT, while 57 research employed RT as their primary training protocol. The subgroup analysis revealed that there was a positive effect on body mass across all subgroups when considering different types of exercise, means that despite of exercise types or even no exercise, creatine can increase body mass.
5.4. Dosage of creatine supplementation
Our results shows that studies using doses up to 5 grams of creatine daily (38 studies), demonstrated a statistically significant decrease in BFP. In this regard, after subgrouping based on dosage, the between subgroups heterogeneity was significant (p=0.005) demonstrating dosage of creatine supplementation is the source of heterogeneity among included studies. however, different dosages did not change the effectiveness of creatine supplementation on FFM and body mass. Future studies should focus on finding the optimum dosage of creatine for attenuating body fat percentages.
5.5. Characteristics of participants that affect body composition indices due to creatine supplementation
Fat-Free Mass
The positive impacts of creatine on FFM were statistically significant irrespective of the age, sex, or whether the individuals were trained or untrained. In addition, participants with a normal body mass index (BMI:18.5 to 24.9) also showed a significant increase in FFM. Also, greater gains in FFM were shown in men. Accordingly, Delpino et al., 2022 did not find any influence from the dosage or type of creatine used or duration of supplementation on fat-free mass. However, they did report greater gains in fat-free mass in males compared to females (males: 1.46kg [95% CI: 0.47, 2.46], females: 0.29kg [95% CI: −0.43, 1.01]) [12]. We also found much larger increases in fat-free mass in males (1.20kg) compared to females (0.54kg). While no sex mechanisms were determined across these reviews, differing results may be associated with differences in pre-supplementation intramuscular creatine levels [191]. There is some evidence that females may have higher intramuscular creatine stores which may blunt their responsiveness to creatine supplementation [192]. Coincidentally, the findings from the subgroup analysis in this research demonstrated a significant augmentation in the impact of creatine supplementation on FFM in studies with a baseline BMI within the normal range. Given that the BMI data was only available for a limited number of individuals in 16 out of the 95 studies that examined the impact of creatine supplementation on FFM, it is important to use care when interpreting this finding.
5.6. Body fat percentage
Our results showed a significant reduction in BFP in trained individuals, while other characteristics of participants did not affect BFP due to Creatine Supplementation. 37 out of 89 studies conducted on trained individuals indicating training background may be a potential factor affecting BFP after creatine supplementation. Although it is not clear to us why trained individuals may benefit more from creatine supplementation, but more FFM gains (1.31kg) in these subjects following creatine supplementation may partially explain the reduction of fat percentage.
5.7. Body Mass
Our analysis examined creatine on body mass and included 154 effect sizes. Overall, participants gained 0.86kg (95% CI: 0.76, 0.96) following creatine supplementation compared to placebo. Trial duration, creatine dose, sex, age, loading protocol, exercise type, type of creatine, and training status did not alter these findings, nor was there any observed heterogeneity between studies. Our findings are partially supported by other systematic reviews and meta-analyses [21,176,193]. For example, Devries and Phillips (2014) conducted a systematic review and meta-analysis in older adults (N=357, across 12 studies) ingesting creatine supplementation combined with resistance training and noted a significant increase in body mass compared to placebo (1.00kg: 95% CI: 0.32–1.67kg; p=0.004) [194]. In contrast, Forbes et al.. (2019) conducted a systematic review and meta-analysis in older adults (N=609, across 19 studies) and found a non-significant increase in body mass (0.86kg: 95% CI, −0.32–2.05kg; p=0.15) [21].
5.8. Strengths and limitations
To our knowledge, this is the first meta-analysis that has evaluated the influence of various supplementation protocols, exercise types, training status, supplementation duration and dose, creatine type, sex, and age on body composition (body mass, fat-free mass, fat mass, body fat percentage and body mass index). Our systematic review included a comprehensive analysis of over 160 effect sizes, which increases the statistical power and certainty of our findings. Nevertheless, it is important to acknowledge limitations. Specifically, we found that a significant number of the RCTs included did not examine baseline intramuscular creatine concentrations or changes in creatine levels throughout the duration of the study, nor did they determine the dietary intake of creatine or total protein. One notable constraint of this meta-analysis was that the majority of studies used body composition measures as a secondary outcome. A further limitation is the absence of adequately structured RCTs that have assessed water retention, hence impeding our ability to elucidate the specific processes behind the increase in body mass and lean mass following to creatine supplementation. In future RCTs, it is warranted to assess both intra and extra-cellular hydration, as well as quantifying the intake of creatine from dietary sources. Additionally, it is crucial to use suitable dosages, exercise modalities, and loading protocols in the design of this research.
6. Conclusion
In summary, creatine supplementation has a very small effect on body mass, fat-free mass, and body fat percentage over time. These changes were apparent when creatine was combined with resistance training. Creatine appears to increase fat-free mass more in males compared to females. Collectively, variations in dosing protocols, training status, and age do not appear to influence the effectiveness of creatine supplementation. Based on previous research findings, which did not report any adverse effects related to the use of creatine supplements on the overall well-being of participants, it seems that people who are apparently healthy may experience benefits from the performance-enhancing properties of creatine supplementation.
Disclosure statement
D.G.C. has conducted industry-sponsored research involving creatine supplementation and received creatine donations for scientific studies and travel support for presentations involving creatine supplementation at scientific conferences. In addition, D.G.C. serves on the Scientific Advisory Board for Alzchem (a company that manufactures creatine) and as an expert witness/consultant in legal cases involving creatine supplementation.
Author contributions
MG, DAL, FD, and RB conceptualized and designed the study, interpreted the data, and prepared the manuscript. OA and MG analyzed the data and drafted the initial manuscript. FP, ZH and KG extracted data and drafted the initial manuscript. SF, FD, RB, and DC supervised the project and edited the initial manuscript. All authors contributed to the article and approved the submitted version.
Ethical approval and consent to participate
This is a review study, and there was no consent to participate.
References
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Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials.
Nutrition, 103-104:111791, 08 Jul 2022
Cited by: 13 articles | PMID: 35986981
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