The present study is the first to demonstrate that creatine supplementation attenuates upper-limb muscle mass and strength loss during cast-induced immobilization in humans. Although the mechanisms explaining the maintenance of muscle mass from creatine are not fully known, creatine has been shown to have a positive effect on satellite cell activity (9,20,25) and muscle protein kinetics (14,16,21,26). In rats undergoing lower-limb compensatory hypertrophy, creatine supplementation significantly increased satellite cell mitotic activity (9), and, in young adults engaged in resistance training, creatine supplementation increased satellite cell and muscle fiber area (20). These results suggest that creatine may alter muscle signaling pathways and possibly increase a favorable environment for muscle growth. Furthermore, creatine may elevate intracellular osmolarity (2) and up-regulate the expression of myogenic transcription factors (i.e., MRF-4, myogenin) directly involved in protein synthesis (2,10,26). For example, in young healthy volunteers, creatine supplementation (20 g·d−1) during 2 weeks of leg immobilization followed by 10 weeks of rehabilitation training significantly increased the expression of myogenic transcription factor MRF-4 and muscle cross-sectional area (14). In addition, creatine supplementation (6 g·d−1) combined with heavy resistance training significantly increased mRNA and protein expression of myogenin and MRF-4 in young men (26). Pertaining to creatine exhibiting anticatabolic properties, Parise et al. (21) have shown that short-term creatine supplementation decreased whole-body protein breakdown (plasma leucine rate of appearance) in young men.
Our findings of greater upper-limb muscle mass maintenance from creatine supplementation during immobilization are in contrast to the findings of Aoki et al. (1) and Hespel et al. (14). Creatine ingestion during 7 days of hind limb immobilization had no effect on soleus and gastrocnemius muscle mass in rats (1), and, in young healthy volunteers, creatine supplementation during 14 days of immobilization had no effect on lower-limb muscle mass over placebo (14). Although it is difficult to compare results across studies, these findings suggest that creatine supplementation may have a greater effect on upper-body muscle mass maintenance over lower-body muscle groups. Interestingly, previous research has suggested that lower-body muscle groups are more negatively affected with physical inactivity and age than upper-body muscle groups (5,18), possibly because of differences in fiber-type distribution and daily recruitment of these muscle groups. Furthermore, differences in creatine supplementation duration, experimental design (repeated measures vs. crossover), and performance measures assessed may also help explain these inconsistent results.
Creatine supplementation has repeatedly been shown to increase muscle strength and endurance when combined with exercise training (3-4,6-8,17). However, results from the present study suggest that creatine supplementation alone may have a favorable effect on muscle strength and endurance performance. Using a similar dosing protocol as the present study, numerous studies have shown that acute creatine supplementation enhances intramuscular creatine and phosphocreatine stores, possibly enhancing the ability to resynthesis ATP and leading to greater force development (12,15,24). Creatine supplementation has been shown to reduce muscle fatigue in young adults (22) and to better maintain maximal torque output over placebo (11). Although intramuscular creatine stores were not assessed, our results may indirectly suggest that creatine supplementation increased creatine and phosphocreatine stores, leading to greater muscle strength and endurance maintenance after immobilization.
In conclusion, the present study displays the ability of oral creatine supplementation to attenuate muscle disuse atrophy and strength loss in the upper limb. One week of immobilization of the upper limb is adequate time to elicit tissue, strength, and endurance changes. These results may have application for individuals suffering from acute muscle injury or disuse. Creatine supplementation may help reduce myoplastic changes directly related to disuse atrophy, thereby facilitating the rehabilitation process. Muscle injury and disuse are common among athletes and exercising individuals. On the basis of these findings, health care practitioners may want to consider creatine as a nonpharmacological intervention to speed the recovery process from force-induced muscle immobilization.
This study was funded by the University Council for Research, St Francis Xavier University, Antigonish, NS, Canada.
1. Aoki, MS, Lima, WP, Miyabara, EH, Gouveia, CH, and Moriscot, AS. Deleterious effects of immobilization upon rat skeletal muscle: role of creatine supplementation. Clin Nutr
23: 1176-1183, 2004.
2. Balsom, PD, Soderland, K, Sjodin, B, and Ekblom, B. Skeletal muscle metabolism during short duration high-intensity exercise
: influence of creatine supplementation. Acta Physiol Scand
154: 303-310, 1995.
3. Burke, DG, Chilibeck, PD, Parise, G, Candow, DG, Mahoney, D, and Tarnopolsky, MA. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc
35: 1946-1955, 2003.
4. Burke, DG, Silver, S, Holt, LE, Smith Palmer, T, Culligan, CJ, and Chilibeck, PD. The effect of continuous low dose creatine supplementation on force, power, and total work. Int J Sport Nutr Exerc Metab
10: 235-244, 2000.
5. Candow, DG and Chilibeck, PD. Differences in size, strength, and power of upper and lower body muscle groups in young and older men. J Gerontol Biol Sci
60: 148-156, 2005.
6. Candow, DG, Chilibeck, PD, Chad, KE, Chrusch, MJ, Davison, KS, and Burke, DG. Effect of ceasing creatine supplementation while maintaining resistance training in older men. J Aging Phys Act
12: 219-231, 2004.
7. Chilibeck, PD, Stride, D, Farthing, JP, and Burke, DG. Effect of creatine ingestion after exercise
on muscle thickness in males and females. Med Sci Sports Exerc
8. Chrusch, MJ, Chilibeck, PD, Chad, KE, Davison, KS, and Burke, DG. Creatine supplementation combined with resistance training in older men. Med Sci Sports Exerc
33: 2111-2117, 2001.
9. Dangott, B, Schultz, E, and Mozdziak, PE. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med
21: 13-16, 2000.
10. Francaux, M and Poortmans, JR. Effects of training and creatine supplement on muscle strength and body mass. Eur J Appl Physiol
80: 165-168, 1999.
11. Greenhaff, PL, Casey, A, Short, AH, Harris, R, Soderland, K, and Hultman, E. Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise
in man. Clin Sci
84: 565-571, 1993.
12. Harris, RC, Soderland, K, and Hultman, E. Elevation of creatine in resting and exercise
muscle of normal subjects by creatine supplementation. Clin Sci
83: 367-374, 1992.
13. Hather, BM, Adams, GR, Tesch, PA, and Dudley, GA. Skeletal muscle responses to lower limb suspension in humans. J Appl Physiol
72: 1493-1498, 1992.
14. Hespel, P, Op't Eijnde, B, Van Leemputte, M, Urso, B, Greenhaff, PL, Labarque, V, Dymarkowski, S, Van Hecke, P, and Richter, EA. Oral creatine supplementation facilitates the rehabilitation
of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol
15: 625-633, 2001.
15. Hultman, E, Soderland, K, Timmons, JA, Cederbald, G, and Greenhaff, PL. Muscle creatine loading in men. J Appl Physiol
81: 232-237, 1996.
16. Ingwall, JS. Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res
38: 115-123, 1976.
17. Kreider, RB, Ferreira, M, Wilson, M, Grindstaff, P, Plisk, S, Reinardy, J, Cantler, E, and Almada, AL. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc
30: 73-82, 1998.
18. Lynch, NA, Metter, EJ, Lindle, RS, Fozard, JL, Tobin, JD, Roy, TA, Fleg, JL, and Hurley, BF. Muscle quality: I. Age-associated differences between arm and leg muscle groups. J Appl Physiol
86: 188-194, 1999.
19. Muller, EA. Influence of training and of inactivity on muscle strength. Arch Phys Med Rehabil
51: 449-462, 1970.
20. Olsen, S, Aagaard, P, Kadi, F, Tufekovic, G, Verney, J, Olesen, JL, Seutta, C, and Kjaer, M. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol
1: 525-534, 2006.
21. Parise, G, Mihic, S, MacLennan, D, Yarasheski, KE, and Tarnopolsky, MA. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol
91: 1041-1047, 2001.
22. Stout, J, Eckerson, J, Ebersole, K, Moore, G, Perry, S, Housh, T, Bull, A, Cramer, J, and Batheja, A. Effect of creatine loading on neuromuscular fatigue threshold. J Appl Physiol
88: 109-112, 2000.
23. Vandenborne, K, Elliott, MA, Walter, GA, Abdus, S, Okereke, E, Shaffer, M, Tahernia, D, and Esterhai, JL. Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation
. Muscle Nerve
21: 1006-1012, 1998.
24. Vanderberghe, K, Gillis, KN, Van Leemputte, M, Van Hecke, P, Vanstapel, F, and Hespel, P. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol
80: 452-457, 1996.
25. Vierck, JL, Icenoggle, DL, Bucci, L, and Dodson, MV. The effects of ergogenic compounds on myogenic satellite cells. Med Sci Sports Exerc
35: 769-776, 2003.
26. Willoughby, DS and Rosene, JM. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med Sci Sports Exerc
35: 923-929, 2003.