Lithuanian University of Health Sciences (Kaunas)
MEDICAL ACADEMY: FACULTY OF NURSING
INSTITUTE OF SPORT
EFFECTIVENESS OF CREATINE
SUPPLEMENTATION IN SPORTS: SYSTEMATIC
LITERATURE REVIEW
Author/Student: Ricardo Barroso Mifsut
Supervisor: Associate professor Alma Kajėnienė
Consultant: Dr. Agnė Slapšinskaitė
TABLE OF CONTENTS:
1. SUMMARY………...………...…….3
2. INTRODUCTION……….……..……….…..4
3. METHODOLOGY..………..………...……..……5
3.1. Search strategy………...………..……....5
3.2. Eligibility criteria (PICO)………...………….………6
3.3 Studies selection……….…….…….………6
3.4. Quality scores of reviewed articles………...…….…….8
4. RESULTS. ……….…..………..9
4.1 Effectiveness of creatine supplementation in sports..……..………...19
4.1.1. Effects on creatine on skeletal muscle hypertrophy……...19
4.1.2. Effects of creatine supplementation on anaerobic exercise…....21
4.1.3. Effects of creatine supplementation on aerobic exercise………22
4.2 Creatine intake protocol. ………...….………..24
4.3 Creatine possible side effects. ………...…….………..25
4.3.1 Dehydration………...…….……….25 4.3.2 Alopecia………...…….………...25 4.3.3 Renal function………..…….………..26 4.3.2 Gastrointestinal funciton………...…….……….27 4.3.5 Interactions……….…….………27 5. Quality of assessment………..28 5. DISCUSION….…………....….….……….………….…….………..30 6. CONCLUSSION.…..……….……….31 7. PRACTICAL RECOMMENDATIONS……….………....33 8. REFERENCES.……..……….………..……..34
1. SUMMARY
Master´s thesis by Ricardo Barroso Mifsut. This is a systematic literature review,
¨Effectiveness of creatine supplementation in sports: Systematic literature review¨.
The aim of this study: to analyze the effects of creatine supplementation in sports in the
last scientific publications (2007-2017). The objectives of this research are: 1. To analyze the effects of creatine supplementation on sports results
2. To analyze the most recommended protocols of creatine supplementation in sports 3. To analyze potential creatine side effects in athletes.
The method of this study: 250 studies were analyzed from which 26 randomized control trials articles (2007-2017) were included from: PubMed, NCBI and Medline¨, keywords: ¨creatine¨, ¨sport¨, ¨supplementation¨, ¨protocol¨, ¨side effects¨, ¨resistance¨, ¨training¨, ¨hypertrophy¨. A 27th article was added to evaluate the quality of the studies. To evaluate the eligibility, PICO criteria was used: Population: No health issues other than their own physical shape/age from all ages and sexes. Intervention: A creatine protocol, commonest form was creatine monohydrated, followed by physical exercises.Comparison: Placebo groups, and in some studies a double blinded course.Outcome: Creatine/placebo physical exercises improvements, muscles biopsies or hormones measurements.
Results of this study: Creatine uptake increases rapidly creatine body stores in its target
tissue, the skeletal muscle, which leads to a quicker regeneration of ATP and IGF-1 between high intensity series of sport exercises. With the length of the exercise the benefits of creatine diminish, that is the reason it could be more beneficial in anaerobic sports and to increase muscle hypertrophy. Golden standard protocol (LD 20g/d x5d MD 5G/d). Finally, the perception of safety can be guaranteed in moderate doses with no significant side effects. Quality evaluation: 13 good, 12 moderate, and 1 poor quality.
Conclusions: 1. Sports results: Creatine uptake creates an increase in the creatine stores right after the loading dose which causes the later improvements in sports performance, more noticed in anaerobic sports. It is regularly reported how heavy resistance training improves if it is associated with creatine supplementation which also leads to changes in muscle morphology, hypertrophy.2. Recommended protocol: Golden standard (LD 20g/d x5d MD 5G/d) 3. Side effects: It is a save supplement, GI discomfort if creatine is taken with doses of 10 grams, if we divide this doses in 2x5 grams the discomfort disappears. Increases DHT, which could accelerate alopecia in sensitive individuals.
ABREVIATIONS
Cr - Creatine PCr - Phosphocreatine CK - Creatine kinase CrM - Creatine monohydrated PL - Placebo LD - Loading dose MD - Maintenance dose GI - GastrointestinalADP - Adenosine diphosphate ATP - Adenosine triphosphate 1RM - One Rep Max
CSA - Cross sectional area LBM - Lean body mass TBW - Total body weigh G1 or G2 – Group1 or Group2 DHT - Dihydrotestosterone PPO - Peak power output MPO - Mean power output FI - Fatigue index
CV - Conduction velocity RCT - Randomized Control Trial
2. INTRODUCTION:
Creatine or methyl guanidine acetic acid is a non-protein organic occurring compound [4, 5] and one of the most used and deeply investigated natural supplements [13]. Many forms of creatine exist [10,25], but most of the studies are focused on the effects of monohydrated creatine [10,14,16,18] on sport performance.
Creatine is a physiologically active substance essential for muscle contraction [1,7,11]. It is a nitrogenous organic acid which is obtained by the body in two possible ways, creatine is produced endogenously and it can be obtained exogenously from ingestion of protein-rich food sources such as seafood and meats [4].
It is made by three amino acids: glycine, arginine and methionine [4], this only occurs when the availability of creatine in the diet is insufficient to meet daily needs (2g/d), after It is produced it will be transported hematogenously till its target organs. In the body, the biggest part of creatine is contained within skeletal muscle [26] which explains the posterior effect on it as it is the primarily target place for loading with supplementation
[4]. The rest of it is stored in brain in which it also can lead to better cognitive performance
[5] and in testes. The normal concentration in muscle is from 100 to 140mmol/kg. Muscle creatine stores break down into creatinine which is filtered and excreted though the kidneys [19].
Creatine is also involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen [5]. Creatine is a critical component of the Cr kinase/phosphocreatine system, in the cell, creatine is phosphorylated to generate phosphocreatine (PCr), an energy substrate that undergoes dephosphorylation to resynthesize ATP from adenosine diphosphate (ADP) [26] in the following reaction: PCr + ADP + H+ Cr + ATP [4, 5].
There is a notably big amount of studies about creatine metabolism and its effects of the human body, uptake protocols, forms of creatine, and possible side effects, these studies proved the efficacy of creatine specially in muscle hypertrophy and anaerobic sports [11,12,13].
Despite this, the mechanisms by which creatine acts in the human metabolism to improve physical exercises performance are still not completely understood.
The aim of this study was to analyze the effects of creatine supplementation in sports in
the last scientific publications (2007-2017).
The objectives of this research are:
1. To analyze the effects of creatine supplementation on sports results
2. To analyze the most recommended protocols of Creatine supplementation in sports 3. To analyze potential creatine side effects in athletes
3. METHODOLOGY
A systematic literature review has been performed to evaluate creatine supplementation effectiveness, used protocols and identify its side effects.
3.1 Search strategy
A systematic literature review was conducted while recollecting studies in three different data bases: PubMed, NCBI and Medline. The publications related with creatine supplementation were identified through key words. Plus, an independent article to evaluate the quality of the studies was included.
Key words: ¨creatine¨, ¨sport¨, ¨supplementation¨, ¨protocol¨, ¨side effects¨, ¨resistance¨,
¨training¨, ¨hypertrophy¨.
3.2 Eligibility criteria (PICO)
Population: The members included in the study were completely healthy individuals with
no health issues other than their own physical shape age. Individuals from all ages and sex were included, although more males than females were included.
Intervention: In all the studies a creatine supplementation protocol was followed by the
participants, the most common creatine form used was creatine monohydrated but other forms were also accepted (i.e., di-creatine citrate/creatine citrate/polyethylene glycosylated creatine). Different protocols of intake were also included. The creatine intake was followed by different types of physical exercises (i.e., aerobic/anaerobic)
Comparison: In all the studies a placebo group was used through different types of
placebo (i.e., glucose/dextrose), and in some studies a double blinded course was used changing only the doses in the creatine group and using again a third group with placebo intake.
Outcome: Different ways of interventions were used, most of were based on giving
creatine supplementation to half of the sample and placebo to the other half.
As well several ways of measurements of the outcomes were made before and after the creatine protocol in all the groups of the studies, such as physical anaerobic/aerobic exercises improvements, muscles biopsies or hormones measurements.
3.3 Studies selection
Study selection was completed between October 2017 and January 2018 including studies made from 2007 till 2017. In total, 251 studies were retrieved and 98 remained after duplicates were removed by a manual check. After titles and abstracts were screened, 61 studies were initially excluded, which left 37, further 10 studies excluded due to not meeting the inclusion criteria (28 articles older than 2007, 19 Articles included comorbidities, 3 Articles were non-human studies, 12 non-English articles).
Thus, a total of 26 studies were included in the final review (see Fig. 1 represents a detailed flow chart of the study selection). This systematic review includes only studies which are Randomized Control Trials studies.
An extra article was included in the review [27] in order to evaluate the quality of the
Fig.1. Flow diagram of article selection
3.4 Quality scores of reviewed articles
We developed a quality assessment key to score the studies. Included studies were scored 0, 1, or 2 for each of the eight scale items with a maximum total score of 16 points. This method is a modified version of Altman DG et al study in which it is explained how a to measure the quality of randomized control trials [27].
Id en ti fi cat ion Sc re eni ng E li gi b il it y In cl u d ed
PubMed, NCBI and Medline Records identified
(n = 251)
Records after duplicates removed (n = 98)
Records screened (n = 37)
Records excluded (n = 61) - 28 articles older than 2007
- 19 Articles included comorbidities - 3 Articles were non human studies - 12 Non English articles
Articles included (n = 27)
Full-text articles excluded
(n = 10)
- 11 Articles with sporadic creatine use.
Overall quality scores were converted to a percentage value and rated (0–49% = poor, 50–89% = moderate, and [90% = good) as seen in table 1.
Table 1. Study quality score key: Total score (16, 100%)
1. What study design was used and, and how were participants allocated?
2 = mixed design, randomized and counterbalanced between conditions
1 = repeated measures/within subjects only OR mixed design but not randomized. 0 = between groups only
2. Was the assigned intervention concealed before allocation?
2 = adequate 1 = unclear
0 = inadequate/impossible
3. Were the outcome assessors blinded to treatment status?
2 = Effective action taken to blind assessors
1 = Small or moderate chance of unbinding of assessors 0 = Not mentioned or not possible
4. Were the inclusion and exclusion criteria clearly defined?
2 = clearly defined 1 = inadequately defined 0 = not defined
5. Were the intervention and control group comparable at entry?
2= good comparability of groups, or confounding adjusted for in analysis/within group design
1= confounding small; mentioned but not adjusted for 0= large potential for confounding, or not discussed
6. Were the interventions clearly defined?
2= clearly defined interventions were applied
1= clearly defined interventions were applied but the application was not standardized 0= intervention and/or application were poorly or not defined
7. Were the outcome measures used clearly defined?
2 = clearly defined
1 = adequately defined/recorded 0 = not adequately defined/recorded
8. Was the follow up period sufficient to measure the effects of the intervention?
2 – active surveillance and appropriate duration 1 – active surveillance, but inadequate duration 0 – surveillance not active or not defined
4. RESULTS
Detailed information was extracted from the 26 studies that met the inclusion criteria for this review (see figure 3).
Included studies were reviewed based on the following characteristics: creatine effectiveness on sport exercises, creatine intake protocols and possible side effects. The number of participants per study ranged from 9 [2] till 77 [25].
Table 2: Studies methods and results
Participants Protocol Method of evaluation Results 1. Cribb PJ, Williams AD, Hayes A. A creatine-protein-carbohydrate supplement enhances responses to resistance training. Med Sci Sports Exerc. 2007 Nov;39(11):1960-8. 31♂ Bodybuilders Age: 25±4 G1 Cr1.5g/kg/d G2 Cr 0,1g/kg/d G3 No Cr
Strength (1RM) body composition, and vastus lateralis muscle biopsies for determination of muscle fiber.
G1 greater improvements in 1RM strength. 40% of the improvements was attributed to hypertrophy. It also showed greater increases in LBM, fiber CSA, and contractile protein compared with G2-3 2. Deldicque L, Atherton P, Patel R, Theisen D, Nielens H, Rennie MJ, Francaux M.Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. J Appl Physiol. 2008 Feb;104(2):371
9♂ Healthy Age:21.7±0.5
G1 Cr 21g/d G2 Maldodext
1RM for each leg on a leg-extension apparatus.
G1 Increased free creatine, phosphorylcreatine, and total Cr levels after Cr supplementation for 5 days.
3. Burke DG, Candow DG, Chilibeck PD, MacNeil LG, Roy BD, Tarnopolsky MA, Ziegenfuss T. Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults. Int J Sport Nutr Exerc Metab. 2008 Aug; 18(4): 289-98. 24♂ 18♀
Active Age: 31±2.6
G1 Cr 0,25/kg/d
G2 Placebo Muscle biopsies (vastus lateralis) were taken before and after the intervention and analyzed for IGF-I
G1 showed increased intramuscular IGF-I content by 67%, with greater accumulation from Cr (+78%)
4. Nunes JP, Ribeiro AS, Schoenfeld BJ, Tomeleri CM, Avelar A, Trindade MC Nabuco HC, Cavalcante EF, Junior PS. Creatine supplementation elicits greater muscle hypertrophy in upper than lower limbs and trunk in resistance-trained men. Nutr Health.2017 Dec;23(4):223-229.
43♂ Resistance trained Age: 22.7±3 G1 LP(4x0,3g/kg/d) 7d MP(0,03g/kg/d) 8w G2 Placebo
Monday and Thursday = pectoral, shoulders, triceps, and abdomen, Tuesday and Friday = back, biceps, thighs, and calves.
Results suggest that Cr supplementation can positively augment muscle hypertrophy in resistance-trained young adult men, particularly in the upper limbs
5. Turner CE, Byblow WD, Gant N Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci. 2015 Jan 28;35(4):1773-80.
15 ♂/♀ Active Age: 21–55
G1 Cr 20g/d x7 d G2 Placebo x7 d
A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of
neuropsychological processes.
Cr supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised.
6. Candow DG, Vogt E, Johannsmeyer S, Forbes SC, Farthing JP . Strategic creatine supplementation and resistance training in healthy older adults. Appl Physiol Nutr Metab. 2015 Jul;40(7):689-94.
26 ♂ 38 ♀
Age: 50-71 G1 x32weeks Cr1 before training 0,1mg/kg
Cr2 after training 0.1mg/kg
G2 Placebo x32w.
Lean tissue and fat mass was measured by dual-energy X-ray absorptiometry.
Leg press and chest press strength were assessed using a 1-repetition maximum (1-RM) standard testing procedure.
Creatine supplementation, independent of the timing of ingestion, increased muscle strength more than placebo.
Compared with resistance training alone, creatine supplementation improves muscle strength, with greater gains in lean tissue mass resulting from post-exercise creatine supplementation.
7. Hespel P, Derave W. Ergogenic effects of creatine in sports and rehabilitation. Subcell Biochem. 2007;46: 245-59 20 ♂/♀ Healthy subjects Age: 26+/-3 G1 LP (20g/d) 7d MP (5g/d) G2 Placebo
3 series of maximal dynamic knee extensions on an isokinetic
dynamometer with 2-min rest pauses in between.
12 maximal isometric contractions with the elbow flexors, interspersed by 10-sec rest intervals
The increase in total creatine content of muscle, already obtained after one week of oral Cr, results in improved maximal muscle torque in repeated contraction series. Cr facilitates muscle glycogen
accumulation. Longer periods of creatine supplementation in
conjunction with resistance training can induce muscle hypertrophy, an aspect that benefits both strength and rehabilitation.
8. Hickner RC, Dyck DJ, Sklar J, Hatley H, Byrd P. Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race. J Int Soc Sports Nutr. 2010 Jul 7;7:26.
12♂ Healthy subjects Age:27.3+/-1
G1 Creatine 3g/d
G2 Placebo Two-hour cycling bout at 60% of peak aerobic capacity (VO2peak) with three 10-second sprints performed at 110% VO2 peak every 15 minutes.
It can be concluded that although creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, and may lead to a reduction in oxygen consumption during submaximal exercise, creatine supplementation does not improve sprint performance at the end of endurance cycling exercise
9. Saremi A, Gharakhanloo R, Sharghi S, Gharaati MR, Larijani B, Omidfar K. Effects of oral creatine and resistance training on serummyostatin and GASP-1. Mol Cell Endocrinol. 2010 Apr 12;317(1-2):25-30.
27♂ Healthy subjects Age: 23.42+/-2.2 G1 LP (20g/d) 7d MP (5g/d) G2 Placebo
3 days per week of training for 8 weeks, each session including three sets of 8–10 repetitions at 60–70% of 1 RM for whole-body exercise. Blood sampling, muscular strength testing and body composition analysis
Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin (p < 0.05), but had not additional effect on GASP-1 (p > 0.05). The effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation.
10. Safdar A, Yardley NJ, Snow R, Melov S, Tarnopolsky MA. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics. 2008 Jan 17;32(2):219-28.
12♂ Healthy subjects Age: 26+/-3 G1 LP (20g/d) 7d MP (5g/d) G2 Placebo
Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen)
CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants (P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in
osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene
expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolality
11. Bazzucchi I, Felici F, Sacchetti M. Effect of short-term creatine supplementation on neuromuscular function. Med Sci Sports Exerc. 2009 Oct;41(10):1934-41 15♂ Trained men Age: 25.2 ± 5.1 G1 Cr 20g/d x 5d
G2 Placebo Isometric maximal voluntary contraction, maximal twitch, force-velocity relationship, and dynamic fatiguing contractions were
assessed in the elbow flexors. Mechanical and EMG signals were recorded and analyzed. CV was estimated from the EMG and used as a parameter of interest.
Maximal twitch was 33.4% higher, and the time to reach the PT was 54.7% lower in CRE than in PLA (P < 0.05). Torque-angular velocity curve was enhanced after Cr supplementation, especially at the higher velocities. Mean fiber CV was, 8.9% higher in CRE after Cr (P < 0.05). EMG did not show significant differences in muscle fatigue
12. Yáñez-Silva A, Buzzachera CF, Piçarro IDC, Januario RSB, Ferreira LHB, McAnulty SR, Utter AC, Souza-Junior TP. Effect of low dose short term creatine supplementation on muscle power output in elite youth soccer players. J Int Soc Sports Nutr. 2017 Feb 7;14:5.
19♂ Soccer players Age: 17.0 ± 0.5 G1 Cr 0,03g/kg/d x14d G2 Placebo
30s Wingate Anaerobic Test to assess peak power output (PPO), mean power output (MPO), fatigue index (FI), and total work.
There were significant increases in both PPO and MPO after the Cr supplementation (P ≤ 0.05) but not the placebo period. There were also significant increases in total work, but not FI, after the Cr
supplementation and placebo periods (P ≤ 0.05). Notably, there were differences in total work between the Cr and placebo groups after (P ≤ 0.05) but not before the 14th day
13. Wang CC, Lin SC, Hsu SC, Yang MT, Chan KH. Effects of Creatine Supplementation on Muscle Strength and Optimal Individual Post-Activation Potentiation Time of the Upper Body in Canoeists. Nutrients. 017 Oct 27;9(11).
19♂ Canoeists Age: 16.75±0.7 G1 Cr 5g/d x6 d G2 Placebo x6 d
Bench row for one rep at max strength and conducted complex training bouts to determine the optimal individual timing of PAP and distance of overhead medicine ball throw before and after the supplementation.
After supplementation, the maximal strength increased (p< 0.05). The optimal individual PAP time in the creatine group was
significantly earlier than the pre-supplementation times (p < 0.05). There was no significant change in explosive power for either group
14. Williams J, Abt G, Kilding AE. Effects of creatine monohydrate supplementation on simulated soccer performance. Int J Sports Physiol Perform. 2014 May;9(3):503-10. 19♂ Soccer players Age: 25.4±4.5 G1 Cr 20d x7 d
G2 Placebo x7 d A Ball-Sport Endurance and Speed Test comprising measures of aerobic ,speed (12- and 20-m sprint), and explosive-power (vertical jump) abilities performed over 90 min was performed pre and post supplementation.
Performance measures during the BEAST deteriorated during the second half relative to the first for both Cr (1.2-2.3%) and placebo (1.0-2.2%) groups, indicating a fatigue effect associated with the BEAST. However, no significant differences existed between groups, suggesting that Cr had no performance-enhancing effect or ability to offset fatigue
15. Smith AE, Fukuda DH, Ryan ED, Kendall KL, Cramer JT, Stout J. Ergolytic/Ergogenic effects of creatine on aerobic power. 2011 Int J Sports Med. Dec;32(12):975-81. 27♂ 28♀ Active Age: 22.2±3.1 G1 Cr 20g/d x5 d G2 Placebo x5 d
Aerobic power (VO2max) was assessed before and after
supplementation using open circuit spirometry during graded exercise tests on a treadmill. 4 high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of peak velocity to determine critical vel.
The results indicated that Cr loading did not positively or negatively influence VO2max, CV, time to exhaustion or body mass (p>0.05). These results suggest Cr supplementation may be used in aerobic running activities without detriments to performance
16. Rahimi R, Mirzaei B, Rahmani-Nia F, Salehi Z. Effects of creatine monohydrate supplementation on exercise-induced apoptosis in athletes: A randomized, double-blind, and placebo-controlled study. J Res Med Sci. 2015 Aug;20(8):7338.
27♂/♀ Athletes Age: 19.52 ± 2.7
G1 Cr 20g/d x7 d
G2 Placebo x7 d Serum p53 and insulin-like growth factor-1 (IGF-1) concentration after acute incremental AE test to
exhaustion. Subjects performed AE before (test 1) and after 7 days of supplementation (test 2).
Before supplementation, AE to exhaustion induced a significant increase in serum p53 and IGF-1 concentrations at both CrM and PL groups (P < 0.05). After supplementation, serum p53 concentrations were significantly lower in CrM than PL at post-AE (P < 0.05). There were no differences in IGF-1
17. Graef JL, Smith AE, Kendall KL, Fukuda DH, Moon JR, Beck TW, Cramer JT, Stout JR. The effects of 4 weeks of creatine supplementation and high-intensity interval training on cardiorespiratory fitness: a randomized controlled trial. J Int Soc Sports Nutr. 2009 Nov 12;6:18.
43♂
Active men Age: 22.6 ± 4.9
G1 Cr 20g/d
G2 Placebo Graded exercise test to determine VO2PEAK, VO2PEAKTTE, and VT. In addition, participants
completed a time to exhaustion ride at 110% of the maximum workload reached during the graded exercise test to determine TWD: TTExW=J.
Significant improvements in VO2PEAK and VO2PEAKTTE occurred in both training groups. Only the Cr group significantly improved VT (16% vs. 10% improvement in PL). No changes occurred in TWD in any group
18. van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clin J Sport Med. 2009 Sep;19(5):399-404.
20♂ Rugby players Age: 18-19 G1 LP: Cr 25/d x7d MP: 5g/d x 14d G2 Placebo
Serum T and DHT were measured and ratio calculated at baseline and after 7 days and 21 days of creatine supplementation (or placebo). Body composition measurements were taken at each time point.
After 7 days of creatine loading, or a further 14 days of creatine maintenance dose, serum T levels did not change. However, levels of DHT increased by 56% after 7 days of creatine loading and remained 40% above baseline after 14 days maintenance (P < 0.001). The ratio of DHT:T also increased by 36% after 7 days creatine supplementation and remained elevated by 22% after the maintenance dose (P < 0.01). 19. Gualano B, Ugrinowitsch C, Novaes RB, Artioli GG, Shimizu MH, Seguro AC, Harris RC, Lancha AH Jr. Effects of creatine supplementation on renal function, a randomized, double controlled clinical trial. Eur J Appl Physiol. 2008 May;103(1):33-40.
18♂ Sedentary Age: 18-35
G1 Cr 10g/d x3m. G2 Placebo x3mths
All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels too.
Cystatin C levels (mg L(-1)) (PRE Cr: 0.82 +/- 0.09; Pl: 0.88 +/- 0.07 vs. POST 12 Cr: 0.71 +/- 0.06; Pl: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in Pl but was unchanged with training in Cr. No significant differences were observed within or between groups in other parameters investigated
The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training.
20. Cancela P, Ohanian C, Cuitiño E, Hackney AC. Creatine supplementation does not affect clinical health markers in football players. Br J Sports Med. 2008 Sep;42(9):731-5 14♂ Football player Age: 19.6 G1 Cr LD15g/d x 3d PD 3g/d x 49d G2 Placebo
Football-training was performed during the study. Total body mass was determined and blood and urine samples were analysed for metabolic, hepatic, renal and muscular function markers, before and after supplementation.
A gain of total body mass was observed after CrM intake, but not with placebo. Blood and urinary markers remained within normal reference values. There were no significant changes in renal and hepatic markers after CrM intake. However, total creatine kinase (CK) activity
significantly increased, and uric acid level tended to decrease after CrM use. Likewise, serum glucose decreased in the Cre group following supplementation. No significant differences in urine parameters were found in either group after supplementation
21. Deminice R, Rosa FT, Pfrimer K, Ferrioli E, Jordao AA, Freitas E.Creatine Supplementation Increases Total Body Water in Soccer Players: a Deuterium Oxide Dilution Study. Int J Sports Med.2016 Feb;37(2):149-53.
13♂ Soccer Players Age: Under20 G1 Cr 0,3g/kg/d x7d G2 Placebo
TBW was determined by deuterium oxide dilution and BIA methods.
7 days of creatine supplementation lead to a large increase in TBW (2.3±1.0 L) determined by deuterium oxide dilution, and a small but significant increase in total body weight (1.0±0.4 kg) in Cr group compared to Pla. The Pla group did not experience any significant changes in TBW or body weight
22. Ostojic SM, Ahmetovic Z. Gastrointestinal distress: after creatine supplementation in athletes: are side effects dose dependent? Res Sports Med. 2008;16(1):15-22. 59♂ Soccer players Age: 25.2±3,7 G1 Cr1 2x5g/d x28d Cr 1x10g/d x28d G2 Placebo x28d
In order to assess potential side effects of the supplementation regimen, all subjects were instructed to report any adverse effects of supplementation on their GI system. Survey questions covered perceived side effects on GI system linked with creatine supplementation
The most frequent GI complaints were diarrhea (39.0%), stomach upset (23.8%), and belching (16.9%). We did not find a significant difference between incidence of GI symptoms between Cr1 and the placebo. Yet, significant differences were found for incidence of diarrhea between the Cr1 and Cr2 groups (28.6% vs. 55.6%, p < 0.05). Moreover, diarrhea was more frequent in the Cr2 group as compared with the placebo (55.6% vs. 35.0%, p < 0.05). There is no reason to believe that creatine supplementation for 28d has any effect on the GIT if taken in 10g/d in two equal doses. The risk of diarrhea may be increased with the intake of 10g per serving
23. Cooke MB, Brabham B, Buford TW, Shelmadine BD, McPheeters M, Hudson GM, Stathis C, Greenwood M, Kreider R, Willoughby DS. Creatine supplementation post-exercise does not enhance training-induced adaptations in middle to older aged males. 2014 Jun;114(6):1321-32. 20♂
Active Age: 55-70
G1 Cr 20g/d
G2 Placebo Body composition and muscle strength measurements, blood collection and vastus lateralis muscle biopsy were completed at 0, 4, 8 and 12 weeks of the
supplement training program.
A significant time effect was observed for 1RM bench press (p = 0.016), leg press (p = 0.012), body mass (p = 0.03), fat-free mass (p = 0.005) and total myofibrillar protein (p = 0.005). A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training (p = 0.08). No supplement interaction effects were observed.
24. Kendall KL, Moon JR, Fairman CM, Spradley BD, Tai CY, Falcone PH, Carson LR, Mosman MM, Joy JM, Kim MP5, Serrano ER, Esposito EN.Ingesting a preworkout supplement containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active men. Nutr Res. 2014 May; 34(5) 442-9
12♂ Trained Age: 28±5 G1Preworkout: Caffeine,creatine, β -alanine, amino acids, and vitB x28d
G2 Placebo
Resting heart rate and BP, body composition, and fasting blood samples were collected before and after . Aerobic capacity as well as muscular strength and endurance were also measured.
No adverse effects were noted for renal and hepatic clinical blood markers, resting heart rate, or BP. Supplements containing similar ingredients and doses should be safe for ingestion periods lasting up to 28 days in healthy, recreationally trained, college-aged men.
25. Camic CL, Housh TJ, Zuniga JM, Traylor DA, Bergstrom HC, Schmidt RJ, Johnson GO, Housh DJ. The effects of polyethylene glycosylated creatine supplementation on anaerobic performance measures and body composition. J Strength Cond Res.2014 Mar; 28(3):825-33
77♂ Soccer players Age: 22.1±2.5 G1 Cr1 1,25g/d x28d Cr2 2,5g/d x28d G2 Placebo x28d
The subjects performed anaerobic performance measures, muscular strength (one-repetition maximum [1RM]), and endurance (80% 1RM) tests for bench press and leg
extension, and underwater
weighing for the determination of body composition at day 0
(baseline), day 14, and day 28.
The results indicated that there were improvements (p < 0.0167) in vertical jump, 20-yard shuttle run, 3-cone drill, muscular endurance for bench press, and body mass for at least one of the PEG-creatine groups without changes for the placebo group. Thus, the present results
demonstrated that PEG-creatine supplementation at 1.25 or 2.50 g·d had an ergogenic effect on lower-body vertical power, agility, change-of-direction ability, upper-body muscular endurance, and body mass
26. Joshua J Gann, Sarah K McKinley-Barnard, Thomas L Andre, Ryan D Schoch, and Darryn S WilloughbyEffects of a traditionally-dosed creatine supplementation protocol and resistance training on the skeletal muscle uptake and whole-body metabolism and retention of creatine in males. J Int Soc Sports Nutr. 2015; 12(Suppl 1): P2.
14♂ Active Ages: 18-30 G1 LP 20-25g/d MD 5-7 g/d G2 Placebo
The participants followed a periodized 4 day per week resistance-training program split into two upper body and two lower body workouts per week, for a total of 7 weeks. Blood and muscle samples were obtained at Day 0, 6, 27, and 48.
Creatine supplementation preferentially induced significant increments in total body mass (p = 0.03) and lean body mass (p = 0.01). Creatine did not significantly decrease fat mass (p = 0.29); however, fat mass was significantly decreased in both groups with resistance training (p = 0.001). Muscle strength significantly increased with resistance training (p = 0.001) for both groups, but was not preferentially increased with creatine supplementation. Creatine supplementation significantly increased muscle total creatine (p = 0.043), serum creatine (p = 0.003), urinary creatine (p = 0.036), and urinary creatinine (p = 0.01) in the creatine group compared to placebo.
27. Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gøtzsche PC, Lang T. ¨The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration¨ . Ann Intern Med. 2001 Apr 17;134(8):663-94
This last article was added in order to evaluate the previous 26th articles quality. From this article, the Study quality score key (Table1) was made with few modifications.
A group of scientists and editors developed the CONSORT (Con solidated S tandards o f R eporting T rials) statement to improve the quality of reporting of RCTs. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical
journals and major international editorial groups have adopted the CONSORT statement. The CONSORT statement facilitates critical appraisal and interpretation of RCTs by providing guidance to authors about how to improve the reporting of their trials. This explanatory and elaboration
4.1 Effectiveness of creatine supplementation in sports
Depending on the type of sport and the goals an athlete wants to achieve we can recommend the uptake of different types of food, the same happens with creatine. Several literatures research have investigated deeper into the anabolic performance enhancing mechanisms of creatine supplementation [8,10,11,12,13] suggesting that these effects may be due to cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signaling [3,7]. The aerobic performance improvement is more controversial with ongoing creatine supplementation [14,15].
In 2010 Saremi A [9] reported a change in myogenic transcription factors when creatine supplementation and resistance training are combined in young healthy males. It was found that serum levels of myostatin, a muscle growth inhibitor, were decreased in the creatine group. Concluding that the effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation.
In spite of very few non-positive, but non-negative, results, it seems that creatine supplementation together with resistance training would increase performance enhancement on maximum and endurance strength as well muscle morphology [1,6,7].
4.1.1 Effects on creatine on skeletal muscle hypertrophy:
One of the commonest use of creatine is to improve and accelerate muscle growth. Cribb PJ [1] in 2007 was the pioneer to show a greater improvement on 1 maximum repetition, muscle body mass, fiber cross sectional area and contractile protein in trained young males when resistance training was combined with a multi-nutrient supplement containing 0.1 g/kg/d of creatine plus 1.5 g/kg/d of protein and carbohydrate compared with just protein itself or a carbohydrate protein supplement without creatine.
This study was the first one to prove improvement in the body composition at a cellular level in resistance trained people with creatine supplementation.
The amount of creatine consumed in this study was higher than other previous studies, making it the perfect dose at that moment to achieved better results, a loading dose of 20g/d followed by a maintenance dose of 5g/d. This dose was later followed by other studies [1,2,3,4,6].
With the same loading dose described before, a year later in Belgium, Deldicque L et al studied and [2] showed a collagen mRNA(250%), GLUT4(45%) and Myosin heavy chain(45%) increase with just 5 days of creatine use, the authors thought that creatine and resistance training favor an anabolic environment by inducing changes in gene expression after only 5 days of supplementation.
The same year another study, Burke DG [3] proved that a combination of creatine supplementation with heavy resistance training increased the concentration of insulin like growth factor (IGF-1), they combined a period of 8 weeks heavy resistance training with a loading protocol of creatine of 0,25g/d/kg followed by a 50 days maintenance phase of 0,06g/kg/d. They did two groups and one subgroup.
• One group took the previously described doses of creatine plus the heavy resistance training and an increment of IGF-1(78%) and body mass (2.2gk). • The other group took placebo instead and their increase of IGF-1(55%) was lower
than those who took creatine and the same happened with their body mass gained (0,6kg)
The increased levels of IGF-1 were associated with the increased creatine pool in the body specially in the muscles as primary target tissue.
The study conclusion suggested that the IGF-1 rise could be due to the effect of creatine incrementing the metabolic rate during the exercises thus incrementing the demand. In a recent interesting study Nunes JP [4] showed that creatine supplementation associated with resistance training produces greater muscular strength improvements in the upper compared with the lower body in randomized 43 resistance trained men over an 8-week study period.
The supplementation protocol included a loading phase (7 days, four doses of 0.3 g/kg per day) and a maintenance phase (7 weeks, single dose of 0.03 g/kg per day).
During the same period, subjects performed resistance training and lean soft tissue of the upper limbs, lower limbs, and trunk was assessed by dual-energy X-ray absorptiometry before and after the intervention.
The Cr group achieved greater results in these outcomes compared with placebo group. For the Cr group, improvements in upper limb (7.1 ± 2.9%) were higher than those observed in lower limbs (3.2 ± 2.1%) and trunk (2.1 ± 2.2%).
But muscle gaining is not only an issue for young healthy people, retention of muscle mass and strength is integral to healthy aging. Candow DG [11] in 2015 performed a study which is encouraging in supporting a role for creatine supplementation during aging by enhancing muscle gain, strength, and functional performance over physical activity alone, but, the limited number of studies indicates further work is needed.
4.1.2 Effects of creatine supplementation on anaerobic exercise
Creatine has regularly proved to increase neuromuscular activity on short duration, mostly anaerobic intermittent exercises by decreasing the resting periods needed.
Bazzucchi I in 2009 [11] observed enhances neuromuscular function of the elbow during both voluntary and electrically induced contractions after creatine uptake.
Flexors in both electrically induced and voluntary contractions but not on endurance performance after 4 loading doses of 5 g creatine plus 15 g maltodextrin for 5/d in young, moderately trained men. Creatine supplementation may facilitate the reuptake of Calcium into the sarcoplasmic reticulum by the action of the Calcium adenosine triphosphate pump, which could enable force to be produced more rapidly through the faster detachment of the actomyosin bridges.
Creatine is mostly known in the lifting world, but it can also improve the performance in other sports such as football [12].
Using a two-group matched, Yáñez-Silva A et al [12] performed a double blind, placebo-controlled design, nineteen male soccer players (17.0 ± 0.5 years) were randomly assigned to either Cr (n = 9) or placebo (n = 10) group.
Before and after supplementation, participants performed a 30s Wingate Anaerobic Test to assess peak power output, mean power output, fatigue index, and total work.
The results showed that there were significant increases in both power output and mean power output after the creatine supplementation period (p ≤ 0.05) but not the placebo period. There were also significant increases in total work, but not fatigue index, after the Cr supplementation and placebo periods (p ≤ 0.05).
Notably, there were differences in total work between the Cr and placebo groups after (p ≤ 0.05) but not before the 14d supplementation period. Which makes us known that creatine can also need a minimum period of time to show results.
In another study, Wang CC [13] examined the effects of creatine supplementation on muscle strength, explosive power, and optimal individual PAP time of the upper body during a set of complex training bouts in canoeists.
Seventeen male high school canoeists performed a bench row for one repetition at maximum strength and conducted complex training bouts to determine the optimal individual timing of PAP and distance of overhead medicine ball throw before and after the supplementation.
Subjects were assigned to a creatine or placebo group, and later consumed 20 g of creatine or carboxymethyl cellulose per day for six days. After supplementation, the maximal strength in the creatine group significantly increased (p < 0.05). The optimal individual PAP time in the creatine group was significantly earlier than the pre-supplementation times (p < 0.05).
There was no significant change in explosive power for either group. The findings support the notion that creatine supplementation increases maximal strength and shortens the optimal individual PAP time of the upper body in high school athletes, but has no effect on explosive power.
Moreover, it was found that the recovery time between a bench row and an overhead medicine ball throw in a complex training bout is an individual phenomenon non-related with creatine intake.
4.1.3 Effects of creatine supplementation on aerobic exercise
Creatine uptake has shown to be completely effective on anaerobic sports exercises, when referring to aerobic exercises there are more doubts about the possible benefits of creatine uptake, nevertheless there is some evidence of its positive or at least not negative effects on endurance aerobic activities.
Creatine monohydrate has been shown to be beneficial to health due to its antioxidant potential. Strenuous exercise is associated with oxidative stress, which could lead to apoptosis. Rahimi R [16] investigated the ability of creatine in amelioration of apoptosis induced by incremental aerobic exercise to exhaustion in young athletes.
Before supplementation, Anaerobic exercise to exhaustion induced a significant increase in serum p53 and IGF-1 concentrations at both creatine and placebo groups (p < 0.05).
After supplementation, serum p53 concentrations were significantly lower in creatine than placebo at post anaerobic exercise (p < 0.05). There were no differences in IGF-1 concentrations between creatine and placebo groups at post aerobic exercise (p > 0.05). The results suggest that supplementation with creatine prevents apoptosis, as measured by decreases in p53 concentration, induced by aerobic exercise to exhaustion in young athletes [16].
In contrast as previously commented creatine does not show the same efficacy in aerobic exercise as it shows in anaerobic exercise [14,15].
In this study [14] Williams J tried to determine the effects of acute short-term creatine supplementation on physical performance during a 90-min soccer specific aerobic performance test.
A double-blind, placebo controlled experimental design was adopted during which 16 male amateur soccer players were required to consume 20 g/d creatine for 7 d or a placebo. A Ball-Sport Endurance and Speed Test (BEAST) comprising measures of aerobic, speed (12- and 20-m sprint), and explosive-power (vertical jump) abilities performed over 90 min was performed pre-supplementation and post supplementation. The results showed that acute short-term creatine supplementation has no beneficial effect on physical measures obtained during a 90-min soccer-simulation test, thus bringing into question its potential as an effective ergogenic aid for soccer players.
In another study, Smith AE [15] showed that creatine supplementation may not alter at all aerobic exercise.
They evaluated the effects of creatine loading and sex differences on aerobic running performance. 27 men and 28 women were randomly assigned to either creatine or a placebo group, ingesting 1 packet 4 times daily (total of 20 g/day) for 5 days.
Aerobic power (maximal oxygen consumption: VO2max) was assessed before and after supplementation using open circuit spirometry during graded exercise tests on a treadmill. 4 high-speed runs to exhaustion were conducted at 110, 105, 100, and 90% of peak velocity to determine critical velocity. Distances achieved were plotted over times-to-exhaustion and linear regression was used to determine the slopes (critical velocity) assessing aerobic performance.
The results indicated that creatine loading did not positively or negatively influence VO2max, critical velocity, time to exhaustion or body mass (p>0.05).
4.2 Creatine intake protocols
Several protocols of creatine supplementation are being used nowadays, in the studies previously exposed different doses and timing were used. The daily oral ingestion of supplementary creatine monohydrate can substantially elevate the creatine content of human skeletal muscle. The major part of the elevation of muscle creatine content is already obtained after one week of supplementation [7].
A typical oral creatine supplementation regimen involving a 5-7 day "loading phase" of 20-25 grams/day followed by a "maintenance phase" of 5-7 grams/day [5,7,9,10,11,12] is typically considered as necessary to adequately saturate skeletal muscle as a lesser dose of creatine is insufficient in doing so. This rationale also assumes that the majority, if not all, of the creatine ingested at this dosage is fully utilized by skeletal muscle as a phosphate reservoir in which to re-synthesize ATP during high-intensity, short-term exercise [26].
Other studies show that using a higher dose of creatine leads to better results [1]. In this study, Cribb PJ et al used two Creatine groups (Cr1.5g/kg/d G2 Cr2 0,1g/kg/d) the first group showed greater improvements in 1RM strength. 40% of the improvements was attributed to hypertrophy. It also showed greater increases in LBM, fiber CSA, and contractile protein compared with the second group and with the placebo.
In another study [1] Candow DG et al studied that creatine supplementation, independent of the timing of ingestion, increased muscle strength more than placebo, they created two subgroups in the Creatine group, the first group took the supplementation before the training and the second group took the supplementation after the creatine, both groups showed significant differences compared to the placebo but no differences were shown between them.
As we will see later creatine has less side effects than other supplements but it starts to show gastrointestinal distress symptoms using a single dose of 10 grams [22] so to avoid gastrointestinal distress the recommendation would be instead of taking doses of 10 grams, to divide them into 5 grams’ doses along the day.
4.3 Creatine possible side effects
A lot of rumors can be heard everywhere were creatine is used about its side effects, intestinal discomfort, kidney damage, or even gastric ulcer, but nothing further from the truth. Several studies have proved the action of creatine on the body which could be considered as side effects.
4.3.1 Dehydration:
Despite the abundance of research suggesting the effectiveness and safety of creatine, a fallacy appears to exist among the general public, driven by media claims and anecdotal reports, that creatine supplementation can result in dehydration.
Several investigated this topic [10,21] specially a recent study made in 2016 by Deminice R et al [21] proved them wrong, they did not just prove that creatine does not lead to dehydration, they proved that creatine promotes hydration by determination the total body water by deuterium oxide dilution and BIA methods. After just 7 days of creatine supplementation, it leads to a large increase in total body water (2.3±1.0 L) and a small but significant increase in total body weight (1.0±0.4 kg) in creatine group compared to the placebo group.
4.3.2 Alopecia:
This could the most known side effect of creatine, people lose hair because hair follicles are blocked by androgenic hormones, which are hormones that control the development of male sexual characteristics - DHT being one of them. These hormones surround the hair follicle, preventing it from absorbing nutrients needed for growth. Over time, the follicle shrinks, and the hair begins to grow in thinner and thinner. Hairs become so thin that they break off easily, resulting in hair loss, and eventually they stop growing altogether. Male baldness is a genetic condition, so it only happens in men who inherited certain types of androgen receptors that result in hair loss when exposed to androgen hormones. In other words, if male baldness pattern runs in your family, chances are higher that you are sensitive to DHT and start to lose your hair if your DHT levels are high.
Van der Merwe J et al [18] investigated resting concentrations of selected androgens after 3 weeks of creatine supplementation in male rugby players. It was hypothesized that the ratio of dihydrotestosterone to testosterone would change with creatine supplementation. After 7 days of creatine loading, and a further 14 days of creatine maintenance dose, serum testosterone levels did not change. However, levels of DHT increased by 56%. From this study, we can explain two possible outcomes:
- A person sensitive to DHT (genetically) will get bald during his life, and as creatine will increase his levels of DHT [18], this process will accelerate the hair loss.
- A person not sensitive to DHT, will not notice any effect because even do DHT levels will be increased by creatine, it will not have any effects on his receptors.
4.3.3 Renal function:
Creatine supplementation as we already know is most commonly used in athletes but in this study Gualano B et al [19] sedentary males submitted to exercise training in order to measure their renal function changes after a period of 3 months. A double blind, placebo controlled trial was performed, serum creatine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. This study concluded no significant differences were observed within or between placebo group and creatine group. The decrease of cystatin C indicates that high dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. The study also showed that the moderate aerobic improved their renal function. In another study [20] Cancela P et al showed similar results, they performed a controlled study where 14 football players were randomly assigned in a double-blinded fashion to Creatine or Placebo. The Creatine group ingested 15 g/day of Creatine monohydrated for 7 days and 3 g/day for the remaining 49 days.
8 weeks of CrM supplementation had no negative effects on blood and urinary clinical health markers in football players. Properties of Creatine may, however, be associated with an increase in CK activity, improving the efficiency for ATP resynthesis, a phenomenon indirectly confirmed by the decreasing tendency in uric acid concentration. Furthermore, CrM seems to slightly influence glucoregulation in trained subjects.
Finally, in another [26] study Deminice R et al showed that higher doses of creatine can cause kidney changes: Loading dose: 20-25g/d x5 days and Maintenance dose 5g/d x49 days, this dosing strategy for creatine supplementation led to excess amounts of serum and urinary creatine and urinary creatinine content.
4.3.4 Gastrointestinal tract:
Some people report gastrointestinal disorders after their creatine intake, to investigate this topic a study from Serbia [22] by Ostojic SM et al collected data from 59 top-level male soccer players who were allocated in a double-blind design to three randomly assigned trials: ingesting creatine supplement (C5: 2 x 5-g doses, and C10: 1 x 10-g dose) or placebo for 28 days. In order to assess potential side effects of the supplementation regimen, all subjects were instructed to report any adverse effects of supplementation on their GI system. There is no reason to believe that short-term oral creatine supplementation for 28 days has any detrimental effect on the GI tract if taken in a recommended amount (2x5g/d). The risk of diarrhea may be increased, however, following intake of 10 grams of creatine per single serving.
4.3.5 Interactions with other supplements:
There is a large number of different supplements that can be consumed with creatine and one could think that it can lead to some non-beneficial health disorder, but in this study [24] Kendall KL et al determined the safety and efficacy of consuming a preworkout supplement containing caffeine, creatine, β-alanine, amino acids, and B vitamins for 28 days.
Concluding that no adverse effects were noted for renal and hepatic clinical blood markers, resting heart rate, or BP. Supplements containing similar ingredients and doses should be safe for ingestion periods lasting up to 28 days in healthy, recreationally trained, college-aged men.
5. Quality of assessment:
Most studies employed a mixed design, randomized and counterbalanced between conditions. These common study designs also allowed most studies to have groups which were comparable at baseline. Adequate descriptions of inclusion/exclusion criteria were lacking in some studies; however, intervention and out- come measures were generally well defined, and the study duration was often adequate.
Thus, overall, quality of studies was good although it could generally be improved by ensuring the use of randomization and a crossover study design and including consistent and clear reporting of inclusion and exclusion criteria.
Overall, thirteen studies achieved a good quality rating, twelve studies received a moderate quality rating, and one study was determined to have a poor-quality rating. Table 1 and table 3 represent the evaluation criterias and the posterior results.
Table 3 Quality of assessment
STUDIES Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 SCORE QUALITY
RATING 1. Cribb PJ et al (2007) 2 2 2 1 2 2 2 2 15 Good 2. Deldicque L et al (2008) 2 2 2 1 1 2 1 1 12 Moderate 3. Burke DG et al (2008) 2 2 1 1 1 1 2 1 11 Moderate 4. Nunes JP et al (2017) 2 2 2 2 2 2 2 1 15 Good 5. Turner CE et al (2015) 2 2 2 1 2 2 2 1 14 Good 6. Candow DG et al (2015) 2 2 2 1 2 2 2 2 15 Good 7. Hespel P et al (2007) 1 1 1 1 1 1 1 1 8 Poor 8. Hickner RC et al (2010) 2 2 2 2 1 2 2 1 14 Good 9. Saremi A et al (2010) 2 2 2 1 2 2 2 1 14 Good 10. Safdar A et al (2008) 2 2 1 1 2 2 2 1 13 Moderate 11. Bazzucchi I et al (2009) 2 2 2 2 2 2 2 1 15 Good 12. YáñezSilva et al (2017) 2 2 2 1 2 2 1 1 13 Moderate 13. Wang CC et al (2017) 2 2 2 1 1 2 1 1 12 Moderate 14. Williams J et al (2014) 2 1 2 1 2 2 2 1 13 Moderate 15. Smith AE et al (2011) 2 2 2 2 2 2 2 1 15 Good 16. Rahimi R et al (2015) 2 2 2 2 2 2 2 1 15 Good 17. Graef JL et al (2009) 2 2 2 1 2 2 2 1 14 Good
18. Van der Merwe J et al
(2009) 2 2 2 1 2 2 1 1 13 Moderate 19. Gualano B et al (2008) 2 2 2 1 2 2 2 1 14 Good 20. Cancela P et al (2008) 2 2 1 1 2 2 2 1 13 Moderate 21. Deminice R et al (2016) 2 2 2 2 2 2 2 1 15 Good 22. Ostojic SM et al (2008) 2 2 2 1 2 2 1 1 13 Moderate 23. Cooke MB et al (2014) 2 2 2 1 1 2 1 1 12 Moderate 24. Kendall KL et al (2014) 2 2 1 1 1 2 1 1 10 Moderate 25. Camic CL et al (2014) 2 2 1 1 2 2 2 1 13 Moderate 26. Joshua J Gann et al (2015) 2 2 2 2 2 2 2 2 16 Good
5. DISCUSSION:
This systematic literature review summarizes and evaluates interventional studies that aimed to study the creatine supplementation effects on different sports and subsequent performance of athletes. Consistent with previous research, there is a large amount of studies that prove the effects of creatine supplementation on physical performance. Candow DG et [2] observed a significant increase in strength performance after creatine intake, independent of the timing of the ingestion, compared with the placebo group. He observed a significant increase in strength performance after 32 weeks of creatine protocol periodized with a concurrent periodized heavy resistance training protocol. It is proved that creatine uptake together with heavy training leads to increased physical performance, fat free mass, and muscle hypertrophy [26]. These effects are thought due to an increased total creatine amount in the body [2] after depleting the creatine stores in the muscles, it causes a quicker ATP regeneration between exercises sets improving the training results. [26].
Recent research has provided greater insight into the anabolic performance enhancing mechanisms of creatine supplementation [11,12,13] suggesting that these effects may be due to satellite cell proliferation and insulin-like growth factor-1 signaling [16]. Cribb PJ et al [1] studied greater improvements in 1RM strength. 40% of the improvements was attributed to hypertrophy. It also showed greater increases in LBM, fiber CSA, and contractile protein compared with the placebo groups, which could also show how creatine benefits the contraction of the muscle.
There is a main protocol in order to achieve the best results from the creatine supplementation, although there are several studies with different doses with at least the same effects.
In summary, the studies included in the present review highlight novel approaches designed to help athletes in specific sports manage their creatine supplementation possible benefits. The studies emphasize not only the importance of a proper protocol performance in athletes, but also highlight feasible strategies to get the best results depending on the type of sport which is performed.
Nevertheless this study is mostly focused on young active healthy males which could have created the perfect physiological environment to achieve the good results that we have reported in this review, maybe the results would have been different if we would have included older adults or people with morbidities and, as we have already mentioned, the creatine physiology in the human body is still not completely understood, those are the main reasons by which further investigation is needed in order obtain the best results from the knowledge of a proper creatine supplementation.
6. CONCLUSION:
According to scientific literature (2007-2017) analyzed in this study we can conclude:
1. Creatine supplementation improves the effects of heavy resistance sport performance, it increases the strength power and hypertrophy of muscles, it produces positive effects on power, hydration, fat free mass, muscle mass gaining and cognitive function independently of the age and sex.
2. Several protocols can be used with similar results, although the Gold Standard protocol of creatine supplementation includes a loading phase of 20 grams of creatine per day during a period not longer than a week, which causes the saturation of creatine stores in its target tissue which is the skeletal muscle, followed by a maintenance dose of 5 grams of creatine per day indefinitely.
3. Creatine consumption is totally safe. The only side effect found was gastrointestinal discomfort when creatine is taken with doses of 10 grams. The increase of dihydrotestosterone can be also considered non-beneficial specially in males sensitive to it, which could accelerate the process of alopecia.
7. PRACTICAL RECOMMENDATIONS
Creatine is a complete safe supplement with great and quick results, with this study we can totally recommend creatine supplementation specially to those athletes performing anaerobic exercises and to those athletes interested in achieve a quicker muscle hypertrophy.
Athletes should use the gold standard protocol (Loading dose 20g/d, Maintenance dose 5g/d) always ingesting a maximum of 5g per dose to avoid any gastrointestinal disorder and if baldness runs in your family it should be considered that creatine may accelerate the process of alopecia due to the increase of dihydrotestosterone.
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