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

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/ ).

Conflict of interest statement

Funding

The project was funded by TI Food and Nutrition, a public–private partnership on precompetitive research in food and nutrition. The researchers were responsible for the study design, data collection and analysis, decision to publish, and preparation of the manuscript. The industrial partners contributed to the project through regular discussion.

Conflict of interest

Evelien M.P. Backx, Roland Hangelbroek, Tim Snijders, Marie-Louise Verscheijden, Lex B. Verdijk, Lisette C.P.G.M. de Groot, and Luc J.C. van Loon have no conflicts of interest.

Figures

Fig. 1

Schematic overview of the study design. 1-RM one-repetition maximum, CT computed tomography

Fig. 2

Individual changes in muscle total creatine at baseline and after 5 days of creatine loading in the creatine group. Responders to creatine supplementation (n = 8) were defined as subjects who showed an increase in muscle total creatine exceeding 10 mmol/kg−1 [10]. Non-responders (n = 6) were defined as subjects who showed no increase in muscle total creatine content or an increase <10 mmol/kg−1 creatine [10]

Fig. 3

Individual changes in body weight in the responders and non-responders following 5 days of creatine loading. Body weight changes are calculated as post-loading minus baseline values

Fig. 4

Changes in cross-sectional area of the quadriceps muscle in the creatine and placebo group following 7 days of one-legged knee immobilization and 7 days of subsequent recovery. Data were analyzed by two-way repeated measures analysis of variance, with time as a within-subjects factor and treatment (creatine and placebo group) as between-subjects factors. Data are expressed as mean ± standard error of the mean. Immobilization resulted in a significant decline in quadriceps cross-sectional area in both groups (asterisk), with no differences between groups. Quadriceps cross-sectional area increased during the recovery week (asterisk), with no differences between groups. CSA cross-sectional area

Fig. 5

Changes in the one-repetition maximum as an estimate of leg muscle strength in the creatine and placebo group, following 7 days of one-legged knee immobilization and 7 days of subsequent recovery. Data were analyzed by two-way repeated measures ANOVA with time as a within-subjects factor and treatment (creatine and placebo group) as between-subjects factors. Data are expressed as means ± standard error of the mean. Immobilization resulted in a significant decline in muscle strength in both groups (asterisk), with no differences between groups. Muscle strength did not change during the recovery week, with no differences between groups. 1-RM one-repetition maximum