Marc Van Leemputte

Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans

1 We investigated the effect of oral creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic transcription factor expression in human subjects. 2 A double‐blind trial was performed in young healthy volunteers (n=22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee‐extension rehabilitation programme (3 sessions week−1, 10 weeks). Half of the subjects received creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P; maltodextrin). 3 Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross‐sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee‐extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters. 4 Immobilization decreased quadriceps muscle CSA (∼10 %) and Wmax (∼25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmax recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor protein expression in neither P nor CR. However, after rehabilitation myogenin protein expression was increased in P but not in CR (P < 0.05), whilst MRF4 protein expression was increased in CR but not in P (P < 0.05). In addition, the change in MRF4 expression was correlated with the change in mean muscle fibre diameter (r=0.73, P < 0.05). 5 It is concluded that oral creatine supplementation stimulates muscle hypertrophy during rehabilitative strength training. This effect may be mediated by a creatine‐induced change in MRF4 and myogenin expression.

Strength training: importance of genetic factors.

PURPOSE This study focuses on the quantification of genetic and environmental factors in arm strength after high-resistance strength training. METHODS Male monozygotic (MZ, N = 25) and dizygotic (DZ, N = 16) twins (22.4 +/- 3.7 yr) participated in a 10-wk resistance training program for the elbow flexors. The evidence for genotype*training interaction, or association of interindividual differences in training effects with the genotype, was tested by a two-way ANOVA in the MZ twins and using a bivariate model-fitting approach on pre- and post-training phenotypes in MZ and DZ twins. One repetition maximum (1RM), isometric strength, and concentric and eccentric moments in 110 degree arm flexion at velocities of 30 degrees x s(-1), 60 degrees x s(-1), and 12 degrees x s(-1) were evaluated as well as arm muscle cross-sectional area (MCSA). RESULTS Results indicated significant positive training effects for all measures except for maximal eccentric moments. Evidence for genotype*training interaction was found for 1RM and isometric strength, with MZ intra-pair correlations of 0.46 and 0.30, respectively. Bivariate model-fitting indicated that about 20% of the variation in post-training 1RM, isometric strength, and concentric moment at 120 degrees x s(-1) was explained by training-specific genetic factors that were independent from genetic factors that explained variation in the pretraining phenotype (30-77%). CONCLUSIONS Genetic correlations between measures of pre- and post-training strength were indicative for high pleiotropic gene action and minor activation of training-specific genes during training.

Phosphocreatine resynthesis is not affected by creatine loading

PURPOSE Oral creatine supplementation has been shown to improve power output during high intensity intermittent muscle contractions. Facilitated muscle phosphocreatine (PCr) resynthesis, by virtue of elevated intracellular PCr concentration, might contribute to this ergogenic action. Therefore, the effect of creatine loading (C: 25 g X d(-1) for 5 d) on muscle PCr breakdown and resynthesis and muscle performance during high intensity intermittent muscle contractions was investigated. METHODS A double-blind randomized cross-over study was performed in young healthy male volunteers (N = 9). 31P-NMR spectroscopy of the m. gastrocnemius and isokinetic dynamometry of knee-extension torque were performed before and after 2 and 5 d of either placebo (P) or C administration. RESULTS Compared with P, 2 and 5 d of C increased (P < 0.05) resting muscle PCr concentration by 11% and 16%, respectively. Furthermore, torque production during maximal intermittent knee extensions, including the first bout of contractions, was increased (P < 0.05) by 5-13% by either 2 or 5 d of C. However, compared with P, the rate of PCr breakdown and resynthesis during intermittent isometric contractions of the calf was not significantly affected by C. CONCLUSION Creatine loading raises muscle PCr concentration and improves performance during rapid and dynamic intermittent muscle contractions. Creatine loading does not facilitate muscle PCr resynthesis during intermittent isometric muscle contractions.

Protective role of {alpha}-actinin-3 in the response to an acute eccentric exercise bout

The ACTN3 gene encodes for the alpha-actinin-3 protein, which has an important structural function in the Z line of the sarcomere in fast muscle fibers. A premature stop codon (R577X) polymorphism in the ACTN3 gene causes a complete loss of the protein in XX homozygotes. This study investigates a possible role for the alpha-actinin-3 protein in protecting the fast fiber from eccentric damage and studies repair mechanisms after a single eccentric exercise bout. Nineteen healthy young men (10 XX, 9 RR) performed 4 series of 20 maximal eccentric knee extensions with both legs. Blood (creatine kinase; CK) and muscle biopsy samples were taken to study differential expression of several anabolic (MyoD1, myogenin, MRF4, Myf5, IGF-1), catabolic (myostatin, MAFbx, and MURF-1), and contraction-induced muscle damage marker genes [cysteine- and glycine-rich protein 3 (CSRP3), CARP, HSP70, and IL-6] as well as a calcineurin signaling pathway marker (RCAN1). Baseline mRNA content of CSRP3 and MyoD1 was 49 + or - 12 and 67 + or - 25% higher in the XX compared with the RR group (P = 0.01-0.045). However, satellite cell number was not different between XX and RR individuals. After eccentric exercise, XX individuals tended to have higher serum CK activity (P = 0.10) and had higher pain scores than RR individuals. However, CSRP3 (P = 0.058) and MyoD1 (P = 0.08) mRNA expression tended to be higher after training in RR individuals compared with XX alpha-actinin-3-deficient subjects. This study suggests a protective role of alpha-actinin-3 protein in muscle damage after eccentric training and an improved stress-sensor signaling, although effects are small.

Resistance training alters torque-velocity relation of elbow flexors in elderly men.

PURPOSE The aim of the study was to compare in vivo dynamic muscle characteristics (torque-velocity relation and maximal contraction velocity) of sedentary young subjects with elderly men before and after training. METHODS Elbow flexion maximal isometric (Tmax) and dynamic torque at velocities between 100 degrees.s-1 and 600 degrees.s-1 were measured, from which maximal contraction velocity was estimated (eVmax). These parameters were obtained from 18 young sedentary subjects (Y) and from 23 healthy sedentary elderly (mean age 63 yr) men (E) before (PRE), after 13 wk (MID), and 26 wk (POST) of moderate intensity resistance training (30RM) of the elbow flexor muscles. RESULTS Y and E before training had similar Tmax, but mean dynamic torque over all velocities was 49.1% higher in Y compared with E. After 13 wk of training TmaxE increased by 8.2% and mean dynamic torque increased by 61.2%, with a velocity dependent gain. For eVmaxE an increase of 21.8% was observed. The second 13-wk training period did not induce further increases. CONCLUSION The results of the present study demonstrate that, after moderate intensity resistance training of healthy elderly men, maximal contraction velocity of elbow flexors (eVmax), estimated from the torque-velocity curve, increased to values observed for sedentary young men.

Predictive power of individual genetic and environmental factor scores.

This study explores the use of an individuals genetic (IGFS) and environmental factor score (IEFS), constructed using genetic model fitting of a multivariate strength phenotype. Maximal isometric and dynamic strength measures, one maximal repetition load (1RM) and muscle cross-sectional area (MCSA) were measured in 25 monozygotic and 16 dizygotic twin pairs. The use of IGFS and IEFS in predicting the sensitivity to environmental stress was evaluated by the association of the scores with strength training gains after a 10-week high resistance strength training programme. Results show a high contribution of genetic factors to the covariation between maximal strength and muscle cross-sectional area (84-97%) at pre-training evaluation. Individual factor scores explained the largest part of the variation in IRM and other strength measures at pre-training and post-training evaluation respectively. Genes that are switched on due to training stress (gene-environment interaction) could explain the decrease in explained variation over time. A negative correlation was found between IGFS and strength training gains (-0.24 to -0.51, P < 0.05); individuals with a high IGFS tend to gain less strength than individuals with low IGFS. Individual environmental factor scores have lower differential power. The predictive value of the IGFS has potential utility in identifying an individuals susceptibility to environmental stress in a variety of multifactorial characteristics, eg diseases and impairments, and for selection of sib pairs for QTL analyses.

Effect of a novel pedal design on maximal power output and mechanical efficiency in well-trained cyclists

Abstract In this study, we evaluated the effects of a novel pedal design, characterized by a downward and forward shift of the cleat fixing platform relative to the pedal axle, on maximal power output and mechanical efficiency in 22 well-trained cyclists. Maximal power output was measured during a series of short (5-s) intermittent sprints on an isokinetic cycle ergometer at cadences from 40 to 120 rev · min−1. Mechanical efficiency was evaluated during a submaximal incremental exercise test on a bicycle ergometer using continuous [Vdot]O2 and [Vdot]CO2 measurement. Similar tests with conventional pedals and the novel pedals, which were mounted on the individual racing bike of the participant, were randomized. Maximal power was greater with novel pedals than with conventional pedals (between 6.0%, sx = 1.5 at 40 rev · min−1 and 1.8%, sx = 0.7 at 120 rev · min−1; P = 0.01). Torque production between crank angles of 60° and 150° was higher with novel pedals than with conventional pedals (P = 0.004). The novel pedal design did not affect whole-body [Vdot]O2 or [Vdot]CO2. Mechanical efficiency was greater with novel pedals than with conventional pedals (27.2%, sx = 0.9 and 25.1%, sx = 0.9% respectively; P = 0.047; effect size = 0.9). In conclusion, the novel pedals can increase maximal power output and mechanical efficiency in well-trained cyclists.

Shortening amplitude affects the incomplete force recovery after active shortening in mouse soleus muscle

Compared to isometric contraction, the force producing capacity of muscle is reduced (force depression, FD) after a work producing shortening phase. It has been suggested that FD results from an inhibition of cross-bridge binding. Because the rate constants of the exponential force (re)development are thought to be primarily determined by cross-bridge attachment/detachment rate, we aimed to investigate the components of force redevelopment (REDEV) after 0.6, 1.2 and 2.4mm shortening, resulting in varying amounts of FD (from about 5% to about 16%), in mouse soleus muscle (n=11). Compared to isometric force development (DEV), the time to reach steady-state during REDEV was about 3 times longer (370 versus 1261ms) increasing with increasing amplitude. Contrary to a single, a double exponential function with one component set equal to the rate constant of DEV (14.3s(-1)), accurately described REDEV (RMS<0.8%). The rate constant of the additional slow component decreased with increasing shortening amplitude and was associated with work delivered during shortening (R(2)=0.75) and FD (R(2)=0.77). We concluded that a work related slow exponential component is induced to the trajectory of incomplete force recovery after shortening, causing FD. These results suggest that after shortening, aside from cross-bridges with normal attachment/detachment rate, cross-bridges with reduced cycling rate are active.

Physiological Adaptations to Hypoxic vs. Normoxic Training during Intermittent Living High

In the setting of “living high,” it is unclear whether high-intensity interval training (HIIT) should be performed “low” or “high” to stimulate muscular and performance adaptations. Therefore, 10 physically active males participated in a 5-week “live high-train low or high” program (TR), whilst eight subjects were not engaged in any altitude or training intervention (CON). Five days per week (~15.5 h per day), TR was exposed to normobaric hypoxia simulating progressively increasing altitude of ~2,000–3,250 m. Three times per week, TR performed HIIT, administered as unilateral knee-extension training, with one leg in normobaric hypoxia (~4,300 m; TRHYP) and with the other leg in normoxia (TRNOR). “Living high” elicited a consistent elevation in serum erythropoietin concentrations which adequately predicted the increase in hemoglobin mass (r = 0.78, P < 0.05; TR: +2.6%, P < 0.05; CON: −0.7%, P > 0.05). Muscle oxygenation during training was lower in TRHYP vs. TRNOR (P < 0.05). Muscle homogenate buffering capacity and pH-regulating protein abundance were similar between pretest and posttest. Oscillations in muscle blood volume during repeated sprints, as estimated by oscillations in NIRS-derived tHb, increased from pretest to posttest in TRHYP (~80%, P < 0.01) but not in TRNOR (~50%, P = 0.08). Muscle capillarity (~15%) as well as repeated-sprint ability (~8%) and 3-min maximal performance (~10–15%) increased similarly in both legs (P < 0.05). Maximal isometric strength increased in TRHYP (~8%, P < 0.05) but not in TRNOR (~4%, P > 0.05). In conclusion, muscular and performance adaptations were largely similar following normoxic vs. hypoxic HIIT. However, hypoxic HIIT stimulated adaptations in isometric strength and muscle perfusion during intermittent sprinting.

The effect of muscle length on force depression after active shortening in soleus muscle of mice

Isometric muscle force after active shortening is reduced [force depression (FD)]. The mechanism is incompletely understood but work delivered during shortening has been suggested to be the main determinant of FD. However, whether muscle length affects the sensitivity of FD to work is unknown, although this information might add to the understanding of the phenomenon. The aim of this study is to investigate the length dependence of the FD/work ratio (Q). Therefore, isometric force production (ISO) of 10 incubated mouse soleus muscles was compared to isometric force after 0.6, 1.2, and 2.4 mm shortening (IAS) at different end lengths ranging from L(0) - 3 to L(0) + 1.8 mm in steps of 0.6 mm. FD was calculated as the force difference between an ISO and IAS contraction at the same activation time (6 s) and end length. We confirm the strong relation between FD and work at L(0) (R² = 0.92) and found that FD is length dependent with a maximum of 8.8 ± 0.3% at L(0) + 1.2 mm for 0.6 mm shortening amplitude. Q was only constant for short muscle lengths (<85% L(0)) but increased exponentially with increasing muscle length. The observed length dependence of Q indicates that FD is not only determined by work produced during shortening but also by a length-dependent factor, possibly actin compliance, which should be incorporated in any mechanism explaining FD.