Muscle inactivity from injury or immobilization leads to a rapid decrease in muscle mass, muscle cross-sectional area, and force-generating capacity. Several studies have shown that muscle CSA of the elbow extensors (20-32%) (23), knee flexors and extensors (7-16%) (13), and ankle plantarflexors (16-26%) (13) is significantly reduced after 6-8 weeks of immobilization, with the greatest reduction in upper-extremity force production (1-6%·d−1) occurring during the first week of immobilization (19).
We have shown on numerous occasions that creatine supplementation during resistance training increases muscle mass and strength (3-4,6-8). Although the overall mechanism behind the molecular effects of creatine supplementation on muscle mass is not totally understood, plausible theories involve an increase in myofibrillar protein kinetics (14,21,26) and satellite cell activity (9,20). Recent evidence suggests that creatine supplementation at rest and during resistance training may be an effective intervention to reverse or maintain lower-body muscle mass during and after an immobilized state. For example, creatine supplementation during 10 weeks of resistance training accelerated the rate of muscle hypertrophy in young adults who previously had their knee flexors immobilized for 2 weeks (14). In addition, creatine supplementation for 14 days during hind limb immobilization minimized the rate of muscle loss in the plantarflexors in the rodent model (1). However, it is unknown whether short-term creatine supplementation will maintain upper-body muscle mass and strength over placebo.
The purpose of this study was to compare the effects of cast-induced immobilization of the upper limb between creatine and placebo interventions. On the basis of the observed reductions in muscle mass (1) and strength after limb immobilization (14), we hypothesized that creatine supplementation would attenuate muscle atrophy and the decrease in strength of the immobilized limb over placebo.
Experimental Approach to the Problem
This study used a single-blind, placebo-controlled, crossover design for 29 days. Days 1-7 and 15-21 were used for the immobilization period, and days 8-14 and 22-29 were used for the recovery period. Subjects were randomized to alternate between their dominant and nondominant arms during immobilization. During days 1-7, each subject had an upper limb immobilized and ingested placebo (4 × 5 g·d−1 maltodextrin). Each subject's upper limb was immobilized at 90° elbow flexion with a long-arm plaster cast by a medical professional. During days 8-14, the cast was removed and subjects were instructed to resume normal daily activities. During days 15-21, each subject had the opposite limb immobilized using the same procedures and supplemented with creatine. Creatine supplementation was divided into 4 equal servings (4 × 5 g) and consumed in the morning, afternoon, evening, and before going to bed. Creatine and placebo (maltodextrin) were mixed with sucrose to mask their identities. Supplements were isoenergetic, isovolumetric, and similar in taste, texture, and appearance. Supplementation compliance was monitored by having subjects return empty supplement bags. During days 22-29, the cast was again removed (Figure 1). The dependent variables of lean tissue mass, elbow flexion/extension strength, and endurance were assessed at baseline, postcast, and after the study.
Seven healthy male subjects (22 years, 182 cm, 81 kg) volunteered for the study. All subjects were creatine naïve for at least 12 weeks before the study and were not performing resistance-type exercise. Subjects agreed not to engage in any weight-bearing or resistance-type exercise and not to change their diets during the study. The study was approved by the university ethics review board for research in human subjects at St. Francis Xavier University, Antigonish, Canada, and all subjects signed an informed consent before the study.
Lean Tissue Mass
Dual-energy X-ray absorptiometry (Hologic QDR-1000/W Whole Body X-ray Bone Densitometer, Bedford, Mass) was used to assess lean tissue mass. Participants were scanned in the supine position along the centerline longitudinal axis of the table. Upper limbs were bent at approximately 45° elbow flexion with the middle metacarpal placed on the iliac of the individual to standardize positioning. The lower limbs were stabilized with a large elastic tied around the toes at the first phalanges. Participants were scanned each testing day. The dual-energy X-ray absorptiometry scans were segmented in a fashion that allowed the arms to be isolated for analysis. Reproducibility was previously determined on 10 subjects, 1 week apart, and measuring the coefficient of variation, defined as the square root of the between-test variance (SD), divided by the combined (marginal) mean of the test results for days 1 and 2, multiplied by 100 (to produce a percentage). The coefficient of variation for lean tissue mass was 0.54%.
Muscular Strength and Endurance
Before the start of the study, subjects performed a familiarization session of 3 sets of isometric and isokinetic elbow flexion and extension contractions to reduce the amount of learning, which may contribute to the increase in strength during the beginning stages of exercise.
To assess muscular strength, a 1-repetition maximum (1RM) isometric bicep curl (IBC) and isometric triceps extension (ITE) were performed with a modified strain gage tensiometer (J.A Preston Corp, New York, NY). Each subject was seated in a specially constructed chair that placed the elbow of the testing arm flexed to 90°, with the upper arm fixed in a vertical position against a flat surface and with the forearm parallel to the floor. The tensiometer was fixed to the seating apparatus with an adjustable cable adjusted to fit the differences in subject height; this individual position was recorded and used each time for subsequent tests. For the IBC, each subject held the hand grip with his forearm and hand supinated. The same body and arm position was used for the ITE, but the subject held the hand grip with his forearm and hand pronated. Once in the respective position for either IBC or ITC, subjects were instructed to perform 3 maximal contractions separated by 3 minutes of rest. Subjects performed 3 contractions continuously for each movement (IBC or ITC); then, after 10 minutes of rest, they performed the opposite movement. The greatest of the 3 attempts was selected to represent the maximal exertion for each of IBC and ITC.
To assess muscular endurance, one set of isokinetic bicep curl and triceps extension was performed using a plate-loaded pulley machine (Hammer Strength, USA) corresponding to a load equal to 60% 1RM, moving in time with a metronome (Whitter MT 400, Korea). The same individualized weight and set cadence was used for each testing session (placebo and creatine). Subjects were instructed to stop when they could no longer maintain pace with the metronome or could not continue because of fatigue. The total number of repetitions performed was used for muscular endurance.
A 2 (group; creatine vs. placebo) × 3 (time; prestudy, postcast, poststudy) analysis of variance with repeated measures on the second factor was used to determine differences between creatine and placebo for lean tissue mass, strength, and endurance. When a significant F value was discovered, Tukey post hoc tests were used to determine differences between means. Values are expressed as mean ± SE. Statistical significance was set at p ≤ 0.05. Data were analyzed using SPSS software (version 13.0; SPSS, Inc., Chicago, Ill).
Lean Tissue Mass
Creatine supplementation (+0.9%) better maintained upper-limb lean tissue mass during immobilization over placebo (−3.7%, p < 0.05; Figure 2). During recovery, creatine resulted in a 0.4% increase in lean tissue mass, and placebo led to a 0.7% increase. There were no significant differences between baseline and recovery measures within and between groups.
Muscle Strength and Endurance
A significant decrease in elbow flexion and extension strength was observed in both groups during immobilization. Compared with placebo, creatine supplementation attenuated the reduction in elbow flexion strength (Cr −4.1% vs. PLA −21.5%, p < 0.05; Figure 3) and elbow extension strength (Cr −3.8% vs. PLA −18.3%, p < 0.05; Figure 4). Creatine supplementation better maintained elbow flexion endurance (Cr −9.6% vs. PLA −43%, p < 0.05; Figure 5) and elbow extension endurance (Cr −6.5% vs. PLA −35%, p < 0.05; Figure 6) compared with placebo.
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.