Scientific Opinion on the substantiation of health claims related to creatine
and increase in physical performance during short-term, high intensity,
repeated exercise bouts (ID 739, 1520, 1521, 1522, 1523, 1525, 1526, 1531,
1532, 1533, 1534, 1922, 1923, 1924), increase in endurance capacity
(ID 1527, 1535), and increase in endurance performance (ID 1521, 1963)
pursuant to Article 13(1) of Regulation (EC) No 1924/2006[sup]1[/sup]
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3
European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe:
Creatine
endurance capacity
endurance performance
exercise
health claims
physical performance
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claims is creatine.
Creatine is a non-essential nitrogenous organic acid that occurs in vertebrates, and it is also synthesised in the human body from L-arginine, glycine and L-methionine. Approximately 95 % of the creatine pool in the body is located in skeletal muscle. The content of creatine in foods can be measured by established methods.
The Panel considers that the food constituent, creatine, which is the subject of the health claims, is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Zwiększenie wydolności fizycznej podczas krótkotrwałych, powtarzających się ćwiczeń o dużej intensywności (ID 739, 1520, 1521, 1522, 1523, 1525, 1526, 1531, 1532, 1533, 1534, 1922, 1923, 1924)
The claimed effects are “energy metabolism”, “muscular effort”, “bodily constitution”, “increasing strength”, “increasing mass”, “increasing power”, “increasing performance”, “muscular effort/recovery”, “increasing time to exhaustion”, and “increasing lifting volume and performance”. The Panel assumes that the target population is adults performing high-intensity exercise.
In the context of the proposed wordings and the references provided, the Panel assumes that the claimed effects refer to an increase in physical performance during short-term, high intensity, repeated exercise bouts. Physical performance relates to the ability to complete certain tasks with higher intensity, faster, or with a higher power output. Muscle mass and strength are major determinants of physical performance. In repeated exercise bouts, physical performance is also related to the ability of muscle to recover faster from high-intensity exercise.
The Panel considers that an increase in physical performance during short-term, high intensity, repeated exercise bouts is a beneficial physiological effect.
2.2. Wzrost wytrzymałości (ID 1527, 1535)
The claimed effect is “increasing workout capacity”. The Panel assumes that the target population is adults performing endurance exercise.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to an increase in endurance capacity. Endurance capacity refers to the exercise time to self-reported fatigue when exercising at a constant workload or speed.
The Panel considers that an increase in endurance capacity is a beneficial physiological effect.
2.3. Zwiększenie wydolności fizycznej (ID 1521, 1963)
The claimed effects are “muscular effort” and “creatine: energy reserve of muscle tissue”. The Panel assumes that the target population is adults performing endurance exercise.
In the context of the proposed wordings, the Panel assumes that the claimed effects refer to an increase in endurance performance (i.e. during longer-term exercise generally at intensity <80 % of maximum O2 consumption). Endurance performance relates to the ability to complete certain tasks with higher intensity, faster, or with a higher power output when performing long-term exercise.
The Panel considers that an increase in endurance performance is a beneficial physiological effect.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka -
The references provided in the consolidated list in relation to the claims evaluated in this opinion included narrative reviews and book chapters which contained no original data for the scientific substantiation of the claims, and abstracts and conference proceedings reporting on human intervention studies in which the information provided regarding the study design, methodology and statistical analyses was insufficient for a full scientific evaluation. Some of the references reported on human intervention studies in which creatine was administered in combination with other food constituents (e.g. carbohydrates, protein, micronutrients and fatty acids) so that the study design did not allow conclusions to be drawn on the effect of creatine alone. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claims.
The references provided also included statements/consensus opinions from authoritative bodies such as the Agence Française de Sécurité Sanitaire des Aliments (AFSSA, 2000), the Scientific Committee on Food (SCF, 2001), and the American College of Sports Medicine (Terjung et al., 2000). Other consensus opinions were published by the International Society of Sports Nutrition (Buford et al., 2007; Kreider et al., 2010) and the American Dietetic Association (Rodriguez et al., 2009). Two meta- analyses of human intervention studies (Branch, 2003; Nissen and Sharp, 2003) and one “systematic review” (Rawson and Volek, 2003) which addressed the effects of creatine consumption on outcome measures relevant to the claimed effects evaluated in this opinion, considered the vast majority of individual human intervention studies submitted for the scientific substantiation of the claims. In addition, three of the references provided which reported on human intervention studies and which addressed the effects of creatine on outcome measures related to the claimed effects evaluated in this opinion were not included in the meta-analyses described below, and will be considered separately as appropriate (Izquierdo et al., 2002; Ostojic, 2004; Syrotuik et al., 2001).
The purpose of the “systematic review” by Rawson and Volek (2003) was to address the effects of creatine supplementation and concurrent resistance training on muscle strength and weight lifting performance. A total of 22 studies, 14 of which were already included in the meta-analysis by Nissen and Sharp (2003), met the inclusion criteria of Rawson and Volek (2003) and the remaining, except three (Stevenson and Dudley, 2001; Syrotuik et al., 2000; Syrotuik et al., 2001), were considered in
the meta-analysis by Branch (2003). Two of the three references were provided in the consolidated list as individual studies (Stevenson and Dudley, 2001; Syrotuik et al., 2001). The Panel notes that the methodology (e.g. literature search or other strategies used to identify pertinent references, and methodology used to calculate average percent estimates for increases in muscle strength and weight lifting performance) used in this review is poorly described and that all the studies included were already considered in the meta-analyses provided or were submitted separately. The Panel considers that no conclusions can be drawn from this review for the scientific substantiation of the claims evaluated in this opinion.
The meta-analysis by Branch (2003) included 96 publications (published up to December 2000) from 100 randomised, placebo-controlled trials, in which at least subjects were blinded to the intervention.
These studies comprised 1,847 subjects. Results were given as means SEM and 95 % CI. Mean
sample size was 19 1 (range 4 to 80). Most of the studies (93 %) were published after 1994, and most (71 % of the studies) were randomised, double-blind, placebo-controlled interventions which
addressed the effect of an acute ( 14 days) creatine loading regimen (19.7 0.5 g creatine for an
average of 9 1 days) on physical performance in mostly young trained (77 % of the studies) men (68 % of the studies). Only 22 studies investigated the effects of low dose maintenance creatine supplementation (>14 days) following acute creatine loading. Twenty-four studies included men and women as subjects. The effect of creatine supplementation on women was the focus in only 9 studies. The primary objective of the meta-analysis was to quantify the effect of creatine supplementation on body composition (including lean body mass) and exercise performance. Performance tasks were classified as single-bout or repetitive-bout exercises. The first bout of repetitive-bout exercises was
classified as a single-bout exercise task. Performance tasks of 30 sec, 30 to 150 sec, and >150 sec were also analysed separately. The effect size (ES) of creatine supplementation variable was calculated for each dependent.
The meta-analysis by Nissen and Sharp (2003) assessed the effects of longer-term creatine supplementation on lean body mass and muscle strength during resistance training. Only randomised, placebo-controlled human intervention studies, published in peer reviewed journals between 1967 and 2001, of at least 3 weeks duration and which involved a full-body resistance-training regimen two or more times per week and were conducted in healthy adults who were not under dietary restriction were included. A total of 18 studies using creatine alone as intervention met the inclusion criteria. These studies included a total of 368 subjects (n=180 in the intervention group and n=188 in the control group) with a mean age of 24 years. All studies had a parallel design, and the sample size in individual studies was generally small (mean n=10 per group). All studies included were published between 1997 and 2001. Three studies included men and women, three studies included women only, and the remaining studies were conducted in men only. Five studies were conducted in untrained subjects, and 13 studies in trained individuals. The studies averaged 7.5 weeks (range 3-13 weeks) in duration. The average loading dose of creatine was 19.4 g/day (range 10-21 g/day) for 5.3 days (range 4-7 days), and the average maintenance dose was 6.7 g/day (range 2-10.5 g/day). Changes in lean mass and strength were normalised for inclusion in the meta-analysis by conversion to percentage change per week for both treatment and placebo groups. Effect sizes (ES) of lean mass and strength changes were calculated for each dependent variable. Duration of tasks and task repetition were not considered in the analysis. All the studies included in this meta-analysis except four (Arciero et al., 2001; Bemben et al., 2001; Chrusch et al., 2001; Jowko et al., 2001) were already considered in the meta-analysis by Branch (2003).
These references will be referred to in different sections of the present evaluation as appropriate.
3.1. Zwiększenie wydolności fizycznej podczas krótkotrwałych, powtarzających się ćwiczeń o dużej intensywności (ID 739, 1520, 1521, 1522, 1523, 1525, 1526, 1531, 1532, 1533, 1534, 1922, 1923, 1924)
The evidence provided by consensus opinions/reports from authoritative bodies and reviews shows that there is good consensus on the role of creatine in increasing physical performance during short- term, high intensity, repeated exercise bouts (AFSSA, 2000; Buford et al., 2007; Kreider et al., 2010; Rodriguez et al., 2009; SCF, 2001; Terjung et al., 2000).
Creatine phosphate (CrP) serves as a readily available source of energy in skeletal muscle and other tissues. For most exercise situations, the demand for adenosine triphosphate (ATP) is predominantly provided through oxidative phosphorylation in the mitochondria. However, when aerobic energy production cannot meet the demand for ATP, anaerobic energy production from CrP hydrolysis and glycogenolysis/glycolysis is required to assist in the provision of ATP. Such cases include the transition from rest to exercise, the transition from one power output to a higher power output, and power outputs above 90-100 % maximal oxygen consumption (VO2max). The rapid re-phosphorylation of adenosine diphosphate (ADP) from CrP via the creatine kinase reaction may buffer changes in ATP during transitions between rest and exercise, and may contribute a substantial fraction of ATP synthesis during short duration, high intensity exercise (AFSSA, 2000; Buford et al., 2007; SCF, 2001; Terjung et al., 2000).
During a bout of high intensity exercise, the relative importance of CrP hydrolysis to ATP synthesis falls off as the exercise duration is increased beyond a few seconds. The greatest improvements in performance following short-term creatine supplementation (5-7 days of ~20 g/day) are found during a series of repetitive, high power output exercise bouts. Exercise performance during the latter bouts of a series (e.g. third, fourth and fifth) can be increased by 5-20 % in very high power output exercise bouts that can be maintained for only a short (seconds) period (e.g. maximal cycling and/or power jumping), and are separated by fairly brief periods of rest (e.g. 20-60 seconds). Therefore, it is likely that creatine supplementation improves exercise performance in sport events which require explosive, high-energy output activities, especially of a repeated nature (AFSSA, 2000; Buford et al., 2007; SCF, 2001; Terjung et al., 2000).
Creatine ingestion increases the total creatine content in human muscle by approximately 15-20 % (mean value), albeit a high inter-individual variability exists. Such increases can be achieved by ingestion of 20 g per day for 4-5 days, but also by ingestion of 3 g per day over a period of one month. The increased creatine content in human muscle is maintained when the ingestion is reduced to 2 g per day after the original loading period. There is a substantial reduction in urine production on the first three days of the loading period and this reduction is coincident with the retention of creatine. The retention of water is thought to be related to an osmotic load caused by creatine retention and to account for the rapid-onset weight gain experienced by many individuals ingesting creatine. Many studies have reported increases in body mass of 1-3 kg following short-term (5-7 days) creatine supplementation (AFSSA, 2000; Buford et al., 2007; SCF, 2001; Terjung et al., 2000).
Longer-term creatine supplementation (e.g. 4 to 12 weeks) in combination with training appears to increase muscle mass and strength as a result of an improved ability to perform high-intensity exercise via increased CrP availability (Buford et al., 2007; SCF, 2001).
The meta-analyses and individual intervention studies provided in the consolidated list are consistent with the above-mentioned consensus. In the meta-analysis by Branch (2003), anaerobic exercise
performance capacity during high-intensity, short-duration exercise ( 30 sec) was significantly
increased by creatine supplementation (617 performance variables; ES=0.24 0.002, 95 % CI=0.20, 0.28; p<0.05), and the majority of the studies considered (45 out of 61) reported an ergonomic effect of creatine. Significantly more repetitions at specific submaximal intensity/workload (21 estimates;
ES=0.64 0.18, 95 % CI=0.27, 1.00, p<0.05) and greater work capacity (83 estimates; ES=0.21 0.05,
95 % CI=0.11, 0.30, n=83, p<0.05) were performed during consumption of creatine compared to placebo. ES for repetitive-bout exercise was significantly higher than for single-bout exercise, and mean ES for percentage decrement in performance over multiple high-intensity bouts was not significantly different from zero (ES= –0.04±0.06; 95 %CI= –0.16, 0.09), suggesting a resistance to fatigue between exercise bouts associated with creatine supplementation. The effect of creatine on overall exercise performance was still significant, but less evident, for tasks lasting 30 to 150 sec
(135 performance estimates; ES=0.19 0.05, 95 % CI=0.10, 0.28; p<0.05), and it was non-significant for tasks lasting more than 150 sec (ES=0.09±0.07; 95 % CI= –0.04, 0.22). On the other hand, the meta-analysis by Nissen and Sharp (2003) supports a positive effect of longer-term (3-13 weeks) creatine supplementation on lean body mass (ES=0.26; 95 % CI=0.17, 0.34, p<0.001) and strength (ES=0.36; CI=0.28, 0.43, p<0.001) during repetitive resistance training, possibly owing to an improved ability to perform high-intensity exercise.
In weighing the evidence, the Panel took into account that there is good consensus on the role of creatine in increasing physical performance during short-term, high intensity, repeated exercise bouts, and that the meta-analyses and individual intervention studies provided in the consolidated list are consistent with this consensus.
The Panel concludes that a cause and effect relationship has been established between the consumption of creatine and an increase in physical performance during short-term, high intensity, repeated exercise bouts.
3.2. Wzrost wytrzymałości (ID 1527, 1535)
Among the references provided in the consolidated list, three reported on individual human intervention studies which investigated the effect of creatine supplementation on continuous (Zoeller et al., 2007) or intermittent (Izquierdo et al., 2002; Ostojic, 2004) endurance cycling or running capacity. Two of the studies tested the effects of an acute creatine load (Izquierdo et al., 2002; Ostojic, 2004), whereas one study used an acute creatine load followed by a creatine maintenance phase (Zoeller et al., 2007).
Izquierdo et al. (2002) investigated the effects of acute creatine supplementation (20 g/day for five days) on endurance capacity in trained male handball players randomly assigned to either creatine (n=9) or placebo (maltodextrin; n=10). Before and after supplementation, subjects performed a maximal multistage discontinuous incremental running test to exhaustion. No significant differences in endurance capacity were observed between the creatine and placebo groups. Ostojic et al. (2004) examined the effects of a seven-day creatine supplementation (30 g/day) vs. placebo (cellulose) on endurance capacity assessed by a maximal multistage 20 m shuttle run test in 20 young soccer players in a randomised parallel study. No significant differences between the creatine and placebo groups
were observed. In the study by Zoeller et al. (2007), 55 men (24.5 5.3 years) were randomly assigned to one of the following supplementation groups for four weeks: placebo (34 g glucose/day, n=13), creatine (5.25 g/day creatine monohydrate plus 34 g glucose, n=12), beta-alanine (n=14), or beta- alanine plus creatine (n=16). Prior to and following supplementation, participants performed a graded exercise test on a cycle ergometer to determine time to exhaustion. The initial power output was set at 30 watts and increased 30 watts every two minutes until the subject could not maintain the required power output at a pedaling rate of 70 rpm, or until volitional termination owing to fatigue. No significant differences in time to exhaustion were observed between groups.
The Panel notes that the three human intervention studies provided did not show an effect of creatine supplementation on measures of endurance capacity. The Panel also notes that there is no consensus on the role of creatine in increasing endurance (aerobic) capacity (AFSSA, 2000; Buford et al., 2007; Kreider et al., 2010; SCF, 2001; Terjung et al., 2000).
In weighing the evidence, the Panel took into account that the three human intervention studies provided from which conclusions could be drawn for the scientific substantiation of the claim did not show an effect of creatine supplementation on measures of endurance capacity.
The Panel concludes that a cause and effect relationship has not been established between the consumption of creatine and an increase in endurance capacity.
3.3. Zwiększenie wydolności fizycznej (ID 1521, 1963)
In the meta-analysis by Branch (2003), half of the studies (nine studies out of 18) which investigated the effect of creatine supplementation on measures of performance during continuous, long-term aerobic exercise (>150 sec) in endurance sports (running and swimming) did not show an effect of creatine supplementation compared to placebo, and the overall effect was not significant (ES=0.09±0.07; 95 % CI= –0.04, 0.22) after exclusion of an outlier with a large ES.
Among the references provided in the consolidated list, one reported on an individual human intervention study which investigated the effect of creatine supplementation on measures of endurance performance (Syrotuik et al., 2001), and was not included in the meta-analysis by Branch (2003).
Syrotuik et al. (2001) randomised 22 rowers to consume either creatine (0.3 g/kg/day for five days followed by a five-week maintenance dose of 0.03 g/kg/day) or placebo together with training (continuous and interval rowing and resistance training 4 and 2 days per week, respectively) for six weeks. No significant differences in repeated power interval performance or 2,000 m rowing times were observed compared to placebo during the five-day creatine loading or the five-week maintenance phases. The Panel notes that this study does not show an effect of creatine supplementation on endurance performance.
The Panel notes that one meta-analysis of 18 human intervention studies, and one additional study, did not show an effect of creatine supplementation on measures of endurance performance. The Panel also notes that there is no consensus on the role of creatine in increasing endurance (aerobic) performance (AFSSA, 2000; Buford et al., 2007; Kreider et al., 2010; SCF, 2001; Terjung et al., 2000).
In weighing the evidence, the Panel took into account that one meta-analysis of 18 human intervention studies, and one additional study, did not show an effect of creatine supplementation on measures of endurance performance.
The Panel concludes that a cause and effect relationship has not been established between the consumption of creatine and an increase in endurance performance.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Zwiększenie wydolności fizycznej podczas krótkotrwałych, powtarzających się ćwiczeń o dużej intensywności (ID 739, 1520, 1521, 1522, 1523, 1525, 1526, 1531, 1532, 1533, 1534, 1922, 1923, 1924)
The Panel considers that the following wording reflects the scientific evidence: “Consumption of creatine increases physical performance during short-term, high intensity, repeated exercise bouts”.
5. Warunki i możliwe ograniczenia stosowania oświadczenia
5.1. Zwiększenie wydolności fizycznej podczas krótkotrwałych, powtarzających się ćwiczeń o dużej intensywności (ID 739, 1520, 1521, 1522, 1523, 1525, 1526, 1531, 1532, 1533, 1534, 1922, 1923, 1924)
The Panel considers that in order to obtain the claimed effect, 3 g of creatine should be consumed daily. The target population is adults performing high-intensity exercise.
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, creatine, which is the subject of the health claims, is sufficiently characterised.
Increase in physical performance during short-term, high intensity, repeated exercise bouts
(ID 739, 1520, 1521, 1522, 1523, 1525, 1526, 1531, 1532, 1533, 1534, 1922, 1923, 1924)
The claimed effects are “energy metabolism”, “muscular effort”, “bodily constitution”, “increasing strength”, “increasing mass”, “increasing power”, “increasing performance”, “muscular effort/recovery”, “increasing time to exhaustion” and “increasing lifting volume and performance”. The target population is assumed to be adults performing high-intensity exercise. In the context of the proposed wordings and the references provided, it is assumed that the claimed effects refer to an increase in physical performance during short-term, high intensity, repeated exercise bouts. An increase in physical performance during short-term, high intensity, repeated exercise bouts is a beneficial physiological effect.
A cause and effect relationship has been established between the consumption of creatine and an increase in physical performance during short-term, high intensity, repeated exercise bouts.
The following wording reflects the scientific evidence: “Consumption of creatine increases physical performance during short-term, high intensity, repeated exercise bouts”.
In order to obtain the claimed effect, 3 g of creatine should be consumed daily. The target population is adults performing high-intensity exercise.
Increase in endurance capacity (ID 1527, 1535)
The claimed effect is “increasing workout capacity”. The target population is assumed to be adults performing endurance exercise. In the context of the proposed wordings, it is assumed that the claimed effect refers to an increase in endurance capacity. An increase in endurance capacity is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of creatine and an increase in endurance capacity.
Increase in endurance performance (ID 1521, 1963)
The claimed effects are “muscular effort” and “creatine: energy reserve of muscle tissue”. The target population is assumed to be adults performing endurance exercise. In the context of the proposed wordings, it is assumed that the claimed effects refer to increase in endurance performance. An increase in endurance performance is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of creatine and an increase in endurance performance.
