Skip to main content
Top
Published in: Sports Medicine 8/2017

Open Access 01-08-2017 | Original Research Article

Creatine Loading Does Not Preserve Muscle Mass or Strength During Leg Immobilization in Healthy, Young Males: A Randomized Controlled Trial

Authors: Evelien M. P. Backx, Roland Hangelbroek, Tim Snijders, Marie-Louise Verscheijden, Lex B. Verdijk, Lisette C. P. G. M. de Groot, Luc J. C. van Loon

Published in: Sports Medicine | Issue 8/2017

Login to get access

Abstract

Background

A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise training.

Objective

Our objective was to investigate whether creatine loading can attenuate the loss of muscle mass and strength during short-term leg immobilization.

Methods

Healthy young men (n = 30; aged 23 ± 1 years; body mass index [BMI] 23.3 ± 0.5 kg/m−2) were randomly assigned to either a creatine or a placebo group. Subjects received placebo or creatine supplements (20 g/d) for 5 days before one leg was immobilized by means of a full-leg cast for 7 days. Muscle biopsies were taken before creatine loading, prior to and immediately after leg immobilization, and after 7 days of subsequent recovery. Quadriceps cross-sectional area (CSA) (computed tomography [CT] scan) and leg muscle strength (one-repetition maximum [1-RM] knee extension) were assessed before and immediately after immobilization and after 1 week of recovery. Data were analyzed using repeated measures analysis of variance (ANOVA). Data are presented consistently as mean ± standard error of the mean (SEM).

Results

There was a significant overall increase in muscle total creatine content following the 5-day loading phase (p = 0.049), which appeared driven by an increase in the creatine group (from 90 ± 9 to 107 ± 4 mmol/kg−1 dry muscle) with no apparent change in the placebo group (from 88 ± 4 to 90 ± 3 mmol/kg−1; p = 0.066 for time × treatment interaction). Quadriceps muscle CSA had declined by 465 ± 59 and 425 ± 69 mm2 (p < 0.01) in the creatine and placebo group, respectively, with no differences between groups (p = 0.76). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the creatine and from 59 ± 3 to 53 ± 3 kg in the placebo group, with no differences between groups (p = 0.20). Muscle fiber size did not change significantly over time in either group (p > 0.05). When non-responders to creatine loading were excluded (n = 6), responders (n = 8; total creatine content increasing from 70 to 106 mmol/kg−1) showed similar findings, with no signs of preservation of muscle mass or strength during immobilization. During the subsequent recovery phase, no differences in muscle mass or strength were found between the two groups (p > 0.05).

Conclusion

Creatine supplementation prior to and during leg immobilization does not prevent or attenuate the loss of muscle mass or strength during short-term muscle disuse.
NIH Clinical Trial Registration Number: NCT01894737 (http://​www.​clinicaltrials.​gov/​).
Literature
1.
go back to reference Suetta C, Hvid LG, Justesen L, Christensen U, Neergaard K, Simonsen L, et al. Effects of aging on human skeletal muscle after immobilization and retraining. J Appl Physiol (1985). 2009;107(4):1172–80. Suetta C, Hvid LG, Justesen L, Christensen U, Neergaard K, Simonsen L, et al. Effects of aging on human skeletal muscle after immobilization and retraining. J Appl Physiol (1985). 2009;107(4):1172–80.
2.
go back to reference Wall BT, Dirks ML, Snijders T, Senden JM, Dolmans J, van Loon LJ. Substantial skeletal muscle loss occurs during only 5 days of disuse. Acta Physiol (Oxf). 2014;210(3):600–11.CrossRefPubMed Wall BT, Dirks ML, Snijders T, Senden JM, Dolmans J, van Loon LJ. Substantial skeletal muscle loss occurs during only 5 days of disuse. Acta Physiol (Oxf). 2014;210(3):600–11.CrossRefPubMed
3.
go back to reference Stevens JE, Walter GA, Okereke E, Scarborough MT, Esterhai JL, George SZ, et al. Muscle adaptations with immobilization and rehabilitation after ankle fracture. Med Sci Sports Exerc. 2004;36(10):1695–701.CrossRefPubMed Stevens JE, Walter GA, Okereke E, Scarborough MT, Esterhai JL, George SZ, et al. Muscle adaptations with immobilization and rehabilitation after ankle fracture. Med Sci Sports Exerc. 2004;36(10):1695–701.CrossRefPubMed
4.
go back to reference Vandenborne K, Elliott MA, Walter GA, Abdus S, Okereke E, Shaffer M, et al. Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation. Muscle Nerve. 1998;21(8):1006–12.CrossRefPubMed Vandenborne K, Elliott MA, Walter GA, Abdus S, Okereke E, Shaffer M, et al. Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation. Muscle Nerve. 1998;21(8):1006–12.CrossRefPubMed
5.
go back to reference Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR. Bed-rest-induced insulin resistance occurs primarily in muscle. Metabolism. 1988;37(8):802–6.CrossRefPubMed Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR. Bed-rest-induced insulin resistance occurs primarily in muscle. Metabolism. 1988;37(8):802–6.CrossRefPubMed
6.
go back to reference Gunther O, Frenzel R. Effect of prolonged physical inactivity on carbohydrate tolerance. Z Gesamte Inn Med. 1969;24(22):814–7.PubMed Gunther O, Frenzel R. Effect of prolonged physical inactivity on carbohydrate tolerance. Z Gesamte Inn Med. 1969;24(22):814–7.PubMed
7.
go back to reference Tzankoff SP, Norris AH. Effect of muscle mass decrease on age-related BMR changes. J Appl Physiol Respir Environ Exerc Physiol. 1977;43(6):1001–6.PubMed Tzankoff SP, Norris AH. Effect of muscle mass decrease on age-related BMR changes. J Appl Physiol Respir Environ Exerc Physiol. 1977;43(6):1001–6.PubMed
8.
go back to reference Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol. 1996;270(4 Pt 1):E627–33.PubMed Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol. 1996;270(4 Pt 1):E627–33.PubMed
9.
go back to reference van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond). 2003;104(2):153–62.CrossRefPubMed van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond). 2003;104(2):153–62.CrossRefPubMed
10.
go back to reference Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994;266(5 Pt 1):E725–30.PubMed Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994;266(5 Pt 1):E725–30.PubMed
11.
go back to reference Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol (1985). 1996;81(1):232–7. Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol (1985). 1996;81(1):232–7.
12.
go back to reference Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand. 1995;154(3):303–10.CrossRefPubMed Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand. 1995;154(3):303–10.CrossRefPubMed
13.
go back to reference Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K, Hultman E. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Lond). 1993;84(5):565–71.CrossRefPubMed Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K, Hultman E. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Lond). 1993;84(5):565–71.CrossRefPubMed
14.
go back to reference Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13(2):198–226.CrossRefPubMed Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13(2):198–226.CrossRefPubMed
15.
go back to reference Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc. 2000;32(2):291–6.CrossRefPubMed Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc. 2000;32(2):291–6.CrossRefPubMed
16.
go back to reference Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc. 2000;32(3):654–8.CrossRefPubMed Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc. 2000;32(3):654–8.CrossRefPubMed
17.
go back to reference 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;37(2):149–53.PubMed 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;37(2):149–53.PubMed
18.
go back to reference Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, et al. Functional significance of cell volume regulatory mechanisms. Physiol Rev. 1998;78(1):247–306.PubMed Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, et al. Functional significance of cell volume regulatory mechanisms. Physiol Rev. 1998;78(1):247–306.PubMed
19.
go back to reference Wall BT, Morton JP, van Loon LJ. Strategies to maintain skeletal muscle mass in the injured athlete: nutritional considerations and exercise mimetics. Eur J Sport Sci. 2015;15(1):53–62.CrossRefPubMed Wall BT, Morton JP, van Loon LJ. Strategies to maintain skeletal muscle mass in the injured athlete: nutritional considerations and exercise mimetics. Eur J Sport Sci. 2015;15(1):53–62.CrossRefPubMed
20.
go back to reference Johnston AP, Burke DG, MacNeil LG, Candow DG. Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res. 2009;23(1):116–20.CrossRefPubMed Johnston AP, Burke DG, MacNeil LG, Candow DG. Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res. 2009;23(1):116–20.CrossRefPubMed
21.
go back to reference Hespel P, Op’t Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol. 2001;536(Pt 2):625–33.CrossRefPubMedPubMedCentral Hespel P, Op’t Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol. 2001;536(Pt 2):625–33.CrossRefPubMedPubMedCentral
22.
go back to reference Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975;35(7):609–16.CrossRefPubMed Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975;35(7):609–16.CrossRefPubMed
23.
go back to reference Frayn K, Maycock P. Skeletal muscle triacylglycerol in the rat: methods for sampling and measurement, and studies of biological variability. J Lipid Res. 1980;21(1):139–44.PubMed Frayn K, Maycock P. Skeletal muscle triacylglycerol in the rat: methods for sampling and measurement, and studies of biological variability. J Lipid Res. 1980;21(1):139–44.PubMed
24.
go back to reference Folch J, Lees M, Sloane Stanley G. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226(1):497–509.PubMed Folch J, Lees M, Sloane Stanley G. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226(1):497–509.PubMed
25.
go back to reference Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol. 2000;89(1):104–10.PubMed Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol. 2000;89(1):104–10.PubMed
26.
go back to reference Strandberg S, Wretling ML, Wredmark T, Shalabi A. Reliability of computed tomography measurements in assessment of thigh muscle cross-sectional area and attenuation. BMC Med Imaging. 2010;10:18.CrossRefPubMedPubMedCentral Strandberg S, Wretling ML, Wredmark T, Shalabi A. Reliability of computed tomography measurements in assessment of thigh muscle cross-sectional area and attenuation. BMC Med Imaging. 2010;10:18.CrossRefPubMedPubMedCentral
27.
go back to reference Verdijk LB, van Loon L, Meijer K, Savelberg HH. One-repetition maximum strength test represents a valid means to assess leg strength in vivo in humans. J Sports Sci. 2009;27(1):59–68.CrossRefPubMed Verdijk LB, van Loon L, Meijer K, Savelberg HH. One-repetition maximum strength test represents a valid means to assess leg strength in vivo in humans. J Sports Sci. 2009;27(1):59–68.CrossRefPubMed
28.
go back to reference Mayhew JL, Prinster JL, Ware JS, Zimmer DL, Arabas JR, Bemben MG. Muscular endurance repetitions to predict bench press strength in men of different training levels. J Sports Med Phys Fit. 1995;35(2):108–13. Mayhew JL, Prinster JL, Ware JS, Zimmer DL, Arabas JR, Bemben MG. Muscular endurance repetitions to predict bench press strength in men of different training levels. J Sports Med Phys Fit. 1995;35(2):108–13.
29.
go back to reference Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, et al. American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc. 2000;32(3):706–17.CrossRefPubMed Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, et al. American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc. 2000;32(3):706–17.CrossRefPubMed
30.
go back to reference Harris RC, Hultman E, Nordesjo LO. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest. 1974;33(2):109–20.CrossRefPubMed Harris RC, Hultman E, Nordesjo LO. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest. 1974;33(2):109–20.CrossRefPubMed
31.
go back to reference Verdijk LB, Koopman R, Schaart G, Meijer K, Savelberg HH, van Loon LJ. Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly. Am J Physiol Endocrinol Metab. 2007;292(1):E151–7.CrossRefPubMed Verdijk LB, Koopman R, Schaart G, Meijer K, Savelberg HH, van Loon LJ. Satellite cell content is specifically reduced in type II skeletal muscle fibers in the elderly. Am J Physiol Endocrinol Metab. 2007;292(1):E151–7.CrossRefPubMed
32.
go back to reference Dirks ML, Wall BT, Snijders T, Ottenbros CL, Verdijk LB, van Loon LJ. Neuromuscular electrical stimulation prevents muscle disuse atrophy during leg immobilization in humans. Acta Physiol (Oxf). 2014;210(3):628–41.CrossRefPubMed Dirks ML, Wall BT, Snijders T, Ottenbros CL, Verdijk LB, van Loon LJ. Neuromuscular electrical stimulation prevents muscle disuse atrophy during leg immobilization in humans. Acta Physiol (Oxf). 2014;210(3):628–41.CrossRefPubMed
33.
go back to reference Syrotuik DG, Bell GJ. Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs. nonresponders. J Strength Cond Res. 2004;18(3):610–7.PubMed Syrotuik DG, Bell GJ. Acute creatine monohydrate supplementation: a descriptive physiological profile of responders vs. nonresponders. J Strength Cond Res. 2004;18(3):610–7.PubMed
34.
go back to reference Wall BT, Snijders T, Senden JM, Ottenbros CL, Gijsen AP, Verdijk LB, et al. Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men. J Clin Endocrinol Metab. 2013;98(12):4872–81.CrossRefPubMed Wall BT, Snijders T, Senden JM, Ottenbros CL, Gijsen AP, Verdijk LB, et al. Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men. J Clin Endocrinol Metab. 2013;98(12):4872–81.CrossRefPubMed
35.
go back to reference Wall BT, van Loon LJ. Nutritional strategies to attenuate muscle disuse atrophy. Nutr Rev. 2013;71(4):195–208.CrossRefPubMed Wall BT, van Loon LJ. Nutritional strategies to attenuate muscle disuse atrophy. Nutr Rev. 2013;71(4):195–208.CrossRefPubMed
36.
go back to reference Nilwik R, Snijders T, Leenders M, Groen BB, van Kranenburg J, Verdijk LB, et al. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Exp Gerontol. 2013;48(5):492–8.CrossRefPubMed Nilwik R, Snijders T, Leenders M, Groen BB, van Kranenburg J, Verdijk LB, et al. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Exp Gerontol. 2013;48(5):492–8.CrossRefPubMed
Metadata
Title
Creatine Loading Does Not Preserve Muscle Mass or Strength During Leg Immobilization in Healthy, Young Males: A Randomized Controlled Trial
Authors
Evelien M. P. Backx
Roland Hangelbroek
Tim Snijders
Marie-Louise Verscheijden
Lex B. Verdijk
Lisette C. P. G. M. de Groot
Luc J. C. van Loon
Publication date
01-08-2017
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 8/2017
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.1007/s40279-016-0670-2

Other articles of this Issue 8/2017

Sports Medicine 8/2017 Go to the issue