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Creatine

Technical Document

Developed by INDI/SNIG for the Irish Sports Council

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Creatine

Databases Pubmed and Google Scholar were searched for human studies published in peer-reviewed

journals from 2009-2014.

Search terms:

‘Creatine’, ‘Creatine Monohydrate’, ‘Athletes’, ‘Sport’, ‘Exercise’.

The reference list from the creatine articles retrieved was searched for any additional papers that were

relevant to the development of this document and the history of creatine in sport.

Inclusion Criteria

Human studies published in English

Healthy subjects

Original investigations assessing the use of creatine and exercise

Incorporated the use of an indistinguishable placebo

Sufficient statistical power

Reviews

Exclusion Criteria

Combined supplement studies

Qualitative studies assessing supplement use in both the general and athletic population

Animal/

in vitro

studies

8 studies and 1 review satisfied the inclusion criteria with findings outlined in table 1.

(For studies published 2006-2009 see table 2)

Introduction

Creatine is a compound derived from amino acids, produced endogenously by the liver and to a lesser

extent by the kidneys and pancreas (Burke

et al.

2003; Cooper

et al.

2012). Creatine is synthesised

from three amino acids, arginine, glycine and methionine that are predominantly located in skeletal

muscle (SM) tissue (Bemben and Lamont 2005).

Following hepatic production, creatine is transported via the circulatory system to target

tissues/organs including the brain and SM. SM is the storage site for approximately 95% of creatine

and here, uptake is primarily facilitated by sodium-chloride-dependent Creat1 transporter proteins that

enable creatine accumulation within SM (Persky e

t al.

2003; Schoch

et al.

2006). However it is

important to recognise that SM creatine stores have a finite capacity owing to the intrinsic

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downregulation of Creat1 transporters, resulting in excretion of excess creatine via urine.

Approximately 60% of creatine exists in its phosphorylated form, phosphocreatine (PCr). There are

many proposed mechanisms of action by which creatine supplementation may promote maximal

performance. These have been reviewed in detail (see Persky

et al.

2003 or Cooper

et al.

2012).

Sources

Creatine can be derived from consumption of a limited range of food products including red meat

(350mg creatine/100g), eggs and fish (Williams, 2007). Alternatively creatine can be obtained by

consuming creatine monohydrate supplements, available in powdered or liquid form. Creatine

monohydrate supplementation has a long history in a wide range of sports including weightlifting,

American football, soccer, handball, track sprinting, squash, track-and-field athletes and cyclists.The

powdered form of creatine appears to be the most commonly used in the literature and also in the

field. Creatine in liquid form has been used in research, but has failed to demonstrate ergogenic

effects when compared with creatine consumed in powder form. This lack of benefit from liquid

creatine supplementation is likely due to the small amount of creatine found in such products (Gill et

al. 2004, Harris et al. 2004). It is also important to recognise that creatine is not stable in solution, and

those products sold in liquid form are unlikely to contain any significant amount of creatine.

Dosage

According to the International Society for Sports Nutrition position statement (2007), the following is

defined as an effective creatine supplementation protocol:

Loading phase of 0.3g/kg/day creatine monohydrbufbate/day for at least 3days

Followed by

3-5g/day to maintain elevated stores

(Buford

et al.

2007)

Proposed benefits

ATP/PCr activity

PCr is an essential component of the ATP/PCr energy system which provides rapid

oxygen-independent energy during the initial 30 seconds of maximal activity. Sports primarily utilising this

system include track sprinting, weightlifting, and athletic events such as high jump and shot put

(Burke et al. 2003).

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Creatine may promote SM hypertrophy by up-regulating anabolic compounds such as insulin-like

growth factor (IGF-1) (Burke

et al.

2008). Creatine supplementation is associated with increased

contractile protein content and SM fibre cross-sectional area, although this does not always translate

into enhanced performance and has only been demonstrated when combined with carbohydrate and

protein (Cribb

et al.

2007).

Glucose transport and glycogen depletion

Glucose transporter proteins (GLUT) facilitate glucose absorption and enable the accumulation of

glycogen within SM stores. Creatine supplementation has been shown to increase the number of these

proteins, suggesting that creatine may hinder early-onset glycogen depletion in endurance athletes

(Cooper

et al.

2012).

Oxidative stress/damage

Recent studies in this field have yielded mixed results depending on the inflammatory marker

analysed, with many showing no beneficial effect of creatine on exercise-induced oxidative

stress/damage (Deminice

et al.

2011; Rahimi 2011). Further studies are required in order to identify or

rule out an antioxidant effect of creatine following intense exercise.

Psychomotor ability

Creatine may help to counter cognitive deficits following sleep deprivation, although causality is yet

to be established (McMorris et al. 2006; Cook

et al.

2011).

Hydration status

It is well documented that creatine consumption results in intracellular water retention, increasing

bodyweight and that this process is catalysed in the presence of carbohydrate. This may be of benefit

to athletes training in hot and humid environments by attenuating thermal and cardiovascular strain

under these conditions (Beis

et al.

2011).

Concerns

Contamination

A recent study highlighted that in 33 commercially available creatine supplements, 50% contained

contaminants including heavy metals, at levels exceeding the maximum limit recommended by the

European Food Safety Authority in 2004 (Moret

et al.

2011). It is therefore advisable to consult a

performance nutritionist before consuming any creatine-based or creatine-containing supplement.

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As mentioned above, creatine promotes intracellular water retention, increasing bodyweight. This

should be taken into account when weight-class athletes are considering creatine supplementation.

Range of movement

A recent study also suggests that intracellular water retention from acute creatine supplementation

may hinder athlete’s upper and lower-body range of movement. The study speculates that this may be

due to the water retention directly or via reduced neural outflow and increase anterior compartment

pressure (Sculthorpe

et al.

2010).

Table 1: Recent Literature Supporting a Role of Creatine Supplementation in Performance

(2009-Present)

Reference Subjects Dose Sport/Exercise Protocol Performance Enhancement Summary Barros et al. (2012) 16 physically active males

20g/day for 7 days (dissolved in 500ml water)

Wingate test Yes Increased anaerobic power, capacity total workload. Reduced fatigue index score Creatine supplementation may contribute to improved maximal anaerobic performance

Cook et al. (2011) 10 elite male rugby players 50 or 100 mg/kg bodyweight creatine (1.5 hours prior to test) Rugby passing skill test

Yes Reduced perception and skill performance, following sleep deprivation was ameliorated following creatine supplementation

Creatine supplementation may benefit athletes that have had limited sleep due to travel

De Oca et al. (2013) 12 male taekwondo players 50mg/kg bodyweight for 6 weeks (dissolved in 500ml water)

Taekwondo No Creatine supplementation increased fat mass but had no effect on anaerobic power

Deminice et al. (2013) 23 male soccer players 0.3g/kg bodyweight for 3 days (tablet form)

6X35m sprint with 10 seconds rest between runs

No Supplementation had no effect on post-exercise homocysteine levels Percario et al. (2012) 9 elite male handball players

20g/day for 5 days followed by 5g/day for 27 days (dissolved in1 00ml water)

Bench press, Inclined Chest Fly, Lat pull down, Seated Row, Shoulder press, Biceps curl, Squatting,

Yes Supplementation resulted in improved muscle strength when compared to placebo and control groups

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Leg Extension.

Rahimi (2011) 27 resistance-trained men

4X5g/day for 7 days 7 sets of 3–6 repetitions of bench press, leg press, lat pull down, seated rows with 80–90% of 1RM

Yes Supplementation reduced biomarkers of oxidative damage and improved athletic performance outcomes compared to a placebo group

Tang et al. (2014)

12 male athletes

12g/day for 15 days followed by a 5 day washout period

100m sprint Yes Supplementation significantly increased bodyweight and biomarkers of glycogen degradation were reduced compared to baseline

Zuniga et al. (2012)

22 healthy men

20g/day for 7 days or a maltodextrin-based placebo Wingate test, 1RM bench press, 1RM leg extension

Yes Supplementation resulted in improved mean power (Wingate test) but had no effect on peak power, strength, bench press, leg extension or bodyweight outcomes.

Table 2: Literature Supporting a Role of Creatine Supplementation in Performance

(2006-2009)

Reference Subjects Dose Sport/Exercise Protocol Performance Enhancement Summary Chilibeck et al. 2007 18 rugby union football players 0.1 g·kg–1·d–1 CrM or placebo per day for 8 weeks.

Players trained 2 x per week for approx 2 hours and played one 80 min game per week.

Yes CrM supplementation during a rugby union season is effective for increasing muscular endurance, but has no effect on body composition or aerobic endurance.

Reardon et al. 2006 13 healthy physically active, 9 male and 4 female. 6g of CrM or placebo 4 x per day for 7 days

4 week endurance training program

No CrM supplementation does not effect metabolic adaptations to endurance training. McMorris et al. 2006 5 male and 13 male sport science students 5g of CrM or placebo 4 times per day for 7 days

Subjects completed tests of random movement generation, verbal and spatial recall, choice reaction time, static balance and

Yes CrM supplementation had a

positive effect on mood state and tasks that place a heavy

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mood state pre-test & after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. McConnell et al 2005 7 well trained males 21g of CrM or placebo per day for 5 days

45 min cycling at 78% VO2peak then a time trial

Yes Increased muscle CrM before exercise improved the ability to maintain energy balance during intense exercise.

Ostojic et al. 2004 20 young male soccer players

3 x 10g doses of CrM or placebo for 7 days.

Soccer specific drills before and after supplementation.

Yes CrM ingestion improved soccer specific drills in young males.

Koenig et al. 2008 60 active males

25g of CrM, carbohydrate or placebo for 5 consecutive days.

Repeated jump height before and after supplementation

Yes The carbohydrate and CrM groups maintained repeated bouts of high-intensity activity as measured by repeated static jumps.

Herda et al. 2009 58 healthy males 5g of CrM, small dose of polyethylene glycosylated creatine, moderate dose of polyethylene glycosylated Creatine or a placebo for 30 days. High intensity anaerobic activities such as 1RM and Wingate assessed before and after supplementation

Yes CrM increased body mass and muscle strength, but did not impact on peak power output, mean power output, or muscle endurance when compared to placebo.

Cramer et al.2007 25 healthy males

10.5g of CrM or placebo 2 x per day for days 1-6 and 1 x per day for days 7-8.

3 days of isokinetic resistance training

Yes Peak torque increased but acceleration decreased from pre to post training.

Wright et al. 2007 10 physically active males

4 x 5g of CrM per day or placebo for 6 days

6 x 10 sec maximal sprints of cycle ergometer in a hot environment

No CrM does not produce any

thermoregulatory responses to intermittent sprint exercises in the heat.

Silva et al. 2007 16 female swimmers

20g of CrM or placebo for 21 days

2 x 25m swimming bouts with 3 min recovery pre and post supplementation

No CrM supplementation produced significant effects on gross and propelling efficiency during swimming but did not influence performance, body composition or body weight. Hoffman et al. 2005 40 physically active males 6g of CrM or placebo for 6 days

Wingate test before and after

No Reduce fatigue rate was seen in subjects supplemented with CrM but no other

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supplementation differences observed. Cornish et al. 2006 17 competitive male ice-hockey players 0.3g of CrM per kg of body mass per day for 5 days or placebo

Repeated sprints till exhaustion on skating treadmill

No CrM was not effective in enhancing performance in ice-hockey players.

Okudan et al. 2005

23 untrained males

5g of CrM or placebo 4 x daily for 6 days

Wingate test before and after

supplementation

Yes CrM supplementation enhanced total power output during the Wingate test.

Cancela et al. 2008 14 male footballer players 15g of CrM or placebo for 7 days, then 3g of CrM or placebo for 49 days.

Football specific training

Not assessed CrM supplementation had no negative effects on blood and urinary clinical health markers. CrM supplementation may be associated with increased creatine in case activity, improving efficiency of ATP resynthesis.

Sale et al. 2009 9 healthy males 4 x 5g·day-1 CrM for 5 days or 20 x 1g·day-1 CrM for 5 days 24 hour urine collections at dat 1-2 and 3-7 post supplementation.

Not assessed Less CrM was excreted when CrM was ingested as 20x 1g doses, which suggests greater retention by the body and probably the muscles. Gotshalk et al. 2008 Thirty 58-71 year old females CrM (0.3g·kg BM) or placebo for 7 days

1RM resistance training assessments + lower body and upper body ergometry.

Yes Short term CrM supplementation resulted in increased strength, power, and lower-body motor functional performance in older women. Levesque et al. 2007 9 male cyclists 20g CrM or placebo per day for 6 days

3 x 25.2km sprint trials with 5 x 200m sprints every 5km.

No CrM did not enhance repetitive sprints when intense activities occur between bouts.

Basta et al. 2006 20 elite rowers

20g of CrM or placebo per day for 5 days then 10g daily for 30 days

Graded rowing on ergometer

No CrM did not increase rowers power on ergometer. Ferguson et al. 2006 26 resistance trained females CrM 0.3g·kg BM for first 7 days then 0.03g·kg BM for the next 9 weeks

Resistance training 4 days per week

No CrM + resistance training did not improve strength or lean body mass more than resistance training only.

Glaister et al. 2006

42 physically active males

5g CrM 4 x per day or placebo for 5 days

15 x 30m sprints repeated at 35 sec intervals

No CrM did not benefit multiple running sprint performances

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Watson et al. 2006

12 active males

21.6g per day of CrM or placebo for 7 days

Once 2% dehydrated, subjects completed an 80 min exercise heat tolerance test which involved 4 min rest, 3 min walk, 1 min high intensity run.

Not applicable Short term CrM did not increase the incidence of symptoms or comprise hydration status in dehydrated men.

Havenetidis et al. 2005

7 male active subjects

25g of CrM for 4 days 3 x Wingate tests Yes CrM Supplementation increased muscle ATP and creatine phosphate and enhanced performance in the Wingate test.

References:

Barros, M.P., Ganini, D., Loren\cco-Lima, L., Soares, C.O., Pereira, B., Bechara, E.J., Silveira,

L.R., Curi, R., Souza-Junior, T.P., 2012. Effects of acute creatine supplementation on iron

homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. Journal of

the International Society of Sports Nutrition 9, 1–10.

Beis, L.Y., Polyviou, T, Malkova, D, Pitsiladis, Y.P., 2011. The Effects of Craetien and Glycerol

Hyperhydration on Running Economy in Well-Trained Endurance Runners. J Int Soc Sport

Nutr. 8:24.

Bemben MG, Lamont HS. Creatine supplementation and exercise performance: recent findings.

Sports Med. 2005;35(2):107-25.

Buford, T.W., Kreider, R.B, Stout, J.R, Greenwood, M, Campbell, B, Spano, M, Ziegenfuss, T,

Lopez, H, Landis, J, Antonio, J., 2007. International Society of Sports Nutrition Position

Stand: Creatine Supplementation and Exercise. J Int Soc Sport Nutr. 4:6

Burke LM and Deakin V. Clinical Sports Nutrition. 2nd ed. Australia: McGraw-Hill Book

Company. (2003). 472-475.

Burke, D.G., Candow, D.G, Chilibeck, P.D, MacNeil, L.G, Roy, B.D, Tarnopolsky, M.A,

Ziegenfuss, T., 2008. Effect of Creatine Supplementation and Resistance Exercise Training

on Muscle Insulin-like Growth Factor in Young Adults. In J Sport Nutr Exerc Metab. 18:

389-98.

Cook, C.J., Crewther, B.T., Kilduff, L.P., Drawer, S., Gaviglio, C.M., 2011. Skill execution and

sleep deprivation: effects of acute caffeine or creatine supplementation-a randomized

placebo-controlled trial. Journal of the international society of sports nutrition 8, 1–8.

Cooper, R., Naclerio, F., Allgrove, J., Jimenez, A., 2012. Creatine supplementation with specific

view to exercise/sports performance: an update. Journal of the International Society of Sports

Nutrition 9, 33.

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Cribb, P.G., Williams, A.D, Hayes, A., 2007. A Creatine-Protein-Carbohydrate Supplement

Enhances Responses to Resistance Training. Med Sci Sports Exerc. 39(11): 1960-8.

De Oca, R.M.-M., Farfán-González, F., Socorro Camarillo-Romero, P., 2013. Efectos de la

suplementación con creatina en practicantes de taekwondo. Nutrición Hospitalaria 28.

Deminice, R., Rosa, F.T., Franco, G.S., Cunha, S.F.C., Freitas, E.C., Jordao, A.A., 2013.

Short-term creatine supplementation does not reduce increased homocysteine concentration induced

by acute exercise in humans. European Journal of Nutrition.

Gill ND, Hall RD, Blazevich AJ. Creatine serum is not as effective as creatine powder for

improving cycle sprint performance in competitive male team-sport athletes. J Strength Cond

Res. 2004;18(2):272-5.

Harris RC, Almada AL, Harris DB, Dunnett M, Hespel P. The creatine content of Creatine Serum

and the change in the plasma concentration with ingestion of a single dose. J Sports Sci. 2004

Sep;22(9):851-7.

McMorris, T., Harris, R.C., Swain, J., Corbett, J., Collard, K., Dyson, R.J., Dye, L., Hodgson, C.,

Draper, N., 2006. Effect of creatine supplementation and sleep deprivation, with mild

exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations

of catecholamines and cortisol. Psychopharmacology 185, 93–103.

Moret, S., Prevarin, A., Tubaro, F., 2011. Levels of creatine, organic contaminants and heavy

metals in creatine dietary supplements. Food Chemistry 126, 1232–1238.

Percário, S., de Tarso Domingues, S.P., Teixeira, L.F.M., Vieira, J.L.F., de Vasconcelos, F.,

Ciarrocchi, D.M., Almeida, E.D., Conte, M., 2012. Effects of creatine supplementation on

oxidative stress profile of athletes. Journal of the International Society of Sports Nutrition 9,

56.

Persky, A.M., Brazeau, G. a & Hochhaus, G., 2003. Pharmacokinetics of the dietary supplement

creatine.

Clinical pharmacokinetics

, 42(6):557–74.

Rahimi, R., 2011. Creatine supplementation decreases oxidative DNA damage and lipid

peroxidation induced by a single bout of resistance exercise. The Journal of Strength &

Conditioning Research 25, 3448–3455.

Schoch, R.D., Willoughby, D. & Greenwood, M., 2006. The regulation and expression of the creatine

transporter: a brief review of creatine supplementation in humans and animals.

Journal of the

International Society of Sports Nutrition

, 3(1):60–66.

Sculthorpe N., Grace F, Jones P, Fletcher I., 2010. The effect of short-term creatine

loading on active range of movement. Appl Physiol Nutr Metab 35:507–511.

Tang, F.-C., Chan, C.-C., Kuo, P.-L., 2013. Contribution of creatine to protein homeostasis in

athletes after endurance and sprint running. European Journal of Nutrition 53, 61–71.

Williams, P.G., 2007. Nutritional composition of red meat.

Nutrition and Dietetics,

64

(4):113-119.

Zuniga, J.M., Housh, T.J., Camic, C.L., Hendrix, C.R., Mielke, M., Johnson, G.O., Housh, D.J.,

Schmidt, R.J., 2012. The effects of creatine monohydrate loading on anaerobic performance

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and one-repetition maximum strength. The Journal of Strength & Conditioning Research 26,

1651–1656.

Figure

Table 1: Recent Literature Supporting a Role of Creatine Supplementation in Performance  (2009-Present)
Table 2: Literature Supporting a Role of Creatine Supplementation in Performance  (2006- (2006-2009)

References

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