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Concept: Muscular system


Nutrient timing is a popular nutritional strategy involves the consumption of combinations of nutrients–primarily protein and carbohydrate–in and around an exercise session. Some have claimed that this approach can produce dramatic improvements in body composition. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients. The post-exercise period is widely considered the most critical part of nutrient timing. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an anabolic “window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations. However, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with respect to anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.

Concepts: Metabolism, Nutrition, Muscle, Nutrient, Vitamin, Ontology, Muscular system, Existence


BACKGROUND: Consumption of moderate amounts of animal-derived protein has been shown to differently influence skeletal muscle hypertrophy during resistance training when compared with nitrogenous and isoenergetic amounts of plant-based protein administered in small to moderate doses. Therefore, the purpose of the study was to determine if the post-exercise consumption of rice protein isolate could increase recovery and elicit adequate changes in body composition compared to equally dosed whey protein isolate if given in large, isocaloric doses. METHODS: 24 college-aged, resistance trained males were recruited for this study. Subjects were randomly and equally divided into two groups, either consuming 48 g of rice or whey protein isolate (isocaloric and isonitrogenous) on training days. Subjects trained 3 days per week for 8 weeks as a part of a daily undulating periodized resistance-training program. The rice and whey protein supplements were consumed immediately following exercise. Ratings of perceived recovery, soreness, and readiness to train were recorded prior to and following the first training session. Ultrasonography determined muscle thickness, dual emission x-ray absorptiometry determined body composition, and bench press and leg press for upper and lower body strength were recorded during weeks 0, 4, and 8. An ANOVA model was used to measure group, time, and group by time interactions. If any main effects were observed, a Tukey post-hoc was employed to locate where differences occurred. RESULTS: No detectable differences were present in psychometric scores of perceived recovery, soreness, or readiness to train (p > 0.05). Significant time effects were observed in which lean body mass, muscle mass, strength and power all increased and fat mass decreased; however, no condition by time interactions were observed (p > 0.05). CONCLUSION: Both whey and rice protein isolate administration post resistance exercise improved indices of body composition and exercise performance; however, there were no differences between the two groups.

Concepts: Whey protein, Myosin, Muscular system, Strength training, Weight training, Exercise physiology, Muscle hypertrophy, Whey


Chronic supplementation with creatine monohydrate has been shown to promote increases in total intramuscular creatine, phosphocreatine, skeletal muscle mass, lean body mass and muscle fiber size. Furthermore, there is robust evidence that muscular strength and power will also increase after supplementing with creatine. However, it is not known if the timing of creatine supplementation will affect the adaptive response to exercise. Thus, the purpose of this investigation was to determine the difference between pre versus post exercise supplementation of creatine on measures of body composition and strength.

Concepts: Muscle, Physical exercise, Cardiac muscle, Glycogen, Myosin, Muscular system, Acetylcholine, Exercise physiology


Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.

Concepts: Protein, Metabolism, Nutrition, Obesity, Muscular system, Strength training, Exercise physiology, Muscle hypertrophy


Protein timing is a popular dietary strategy designed to optimize the adaptive response to exercise. The strategy involves consuming protein in and around a training session in an effort to facilitate muscular repair and remodeling, and thereby enhance post-exercise strength- and hypertrophy-related adaptations. Despite the apparent biological plausibility of the strategy, however, the effectiveness of protein timing in chronic training studies has been decidedly mixed. The purpose of this paper therefore was to conduct a multi-level meta-regression of randomized controlled trials to determine whether protein timing is a viable strategy for enhancing post-exercise muscular adaptations. The strength analysis comprised 478 subjects and 96 ESs, nested within 41 treatment or control groups and 20 studies. The hypertrophy analysis comprised 525 subjects and 132 ESs, nested with 47 treatment or control groups and 23 studies. A simple pooled analysis of protein timing without controlling for covariates showed a small to moderate effect on muscle hypertrophy with no significant effect found on muscle strength. In the full meta-regression model controlling for all covariates, however, no significant differences were found between treatment and control for strength or hypertrophy. The reduced model was not significantly different from the full model for either strength or hypertrophy. With respect to hypertrophy, total protein intake was the strongest predictor of ES magnitude. These results refute the commonly held belief that the timing of protein intake in and around a training session is critical to muscular adaptations and indicate that consuming adequate protein in combination with resistance exercise is the key factor for maximizing muscle protein accretion.

Concepts: Metabolism, Energy, Muscle, Physical exercise, Actin, Tissues, Muscular system, Exercise physiology


Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host–graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.

Concepts: Myocardial infarction, Cardiology, Heart, Muscle, Cardiac muscle, Cardiac electrophysiology, Muscular system, Ventricular fibrillation


While intermittent hypoxic training (IHT) has been reported to evoke cellular responses via hypoxia inducible factors (HIFs) but without substantial performance benefits in endurance athletes, we hypothesized that repeated sprint training in hypoxia could enhance repeated sprint ability (RSA) performed in normoxia via improved glycolysis and O(2) utilization. 40 trained subjects completed 8 cycling repeated sprint sessions in hypoxia (RSH, 3000 m) or normoxia (RSN, 485 m). Before (Pre-) and after (Post-) training, muscular levels of selected mRNAs were analyzed from resting muscle biopsies and RSA tested until exhaustion (10-s sprint, work-to-rest ratio 1∶2) with muscle perfusion assessed by near-infrared spectroscopy. From Pre- to Post-, the average power output of all sprints in RSA was increased (p<0.01) to the same extent (6% vs 7%, NS) in RSH and in RSN but the number of sprints to exhaustion was increased in RSH (9.4±4.8 vs. 13.0±6.2 sprints, p<0.01) but not in RSN (9.3±4.2 vs. 8.9±3.5). mRNA concentrations of HIF-1α (+55%), carbonic anhydrase III (+35%) and monocarboxylate transporter-4 (+20%) were augmented (p<0.05) whereas mitochondrial transcription factor A (-40%), peroxisome proliferator-activated receptor gamma coactivator 1α (-23%) and monocarboxylate transporter-1 (-36%) were decreased (p<0.01) in RSH only. Besides, the changes in total hemoglobin variations (Δ[tHb]) during sprints throughout RSA test increased to a greater extent (p<0.01) in RSH. Our findings show larger improvement in repeated sprint performance in RSH than in RSN with significant molecular adaptations and larger blood perfusion variations in active muscles.

Concepts: Hemoglobin, Oxygen, Carbon dioxide, Peroxisome proliferator-activated receptor, Red blood cell, Muscle, Muscular system, Carbonic anhydrase


The purpose of this experiment was to investigate skeletal muscle blood flow and glucose uptake in m. biceps (BF) and m. quadriceps femoris (QF) 1) during recovery from high intensity cycle exercise, and 2) while wearing a compression short applying ∼37 mmHg to the thigh muscles. Blood flow and glucose uptake were measured in the compressed and non-compressed leg of 6 healthy men by using positron emission tomography. At baseline blood flow in QF (P = 0.79) and BF (P = 0.90) did not differ between the compressed and the non-compressed leg. During recovery muscle blood flow was higher compared to baseline in both compressed (P<0.01) and non-compressed QF (P<0.001) but not in compressed (P = 0.41) and non-compressed BF (P = 0.05; effect size = 2.74). During recovery blood flow was lower in compressed QF (P<0.01) but not in BF (P = 0.26) compared to the non-compressed muscles. During baseline and recovery no differences in blood flow were detected between the superficial and deep parts of QF in both, compressed (baseline P = 0.79; recovery P = 0.68) and non-compressed leg (baseline P = 0.64; recovery P = 0.06). During recovery glucose uptake was higher in QF compared to BF in both conditions (P<0.01) with no difference between the compressed and non-compressed thigh. Glucose uptake was higher in the deep compared to the superficial parts of QF (compression leg P = 0.02). These results demonstrate that wearing compression shorts with ∼37 mmHg of external pressure reduces blood flow both in the deep and superficial regions of muscle tissue during recovery from high intensity exercise but does not affect glucose uptake in BF and QF.

Concepts: Heart, Positron emission tomography, Muscle, Cardiac muscle, Glycogen, Muscular system


Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

Concepts: Metabolism, Muscle, Glycogen, Actin, Myosin, Muscular system, Acetylcholine, Neuromuscular disease


Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of childhood marked by progressive debilitating muscle weakness and wasting, and ultimately death in the second or third decade of life. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. We investigated the therapeutic potential of the secreted factor Wnt7a for focal treatment of dystrophic DMD muscles using the mdx mouse model, and found that Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in mdx mice. Importantly, Wnt7a treatment resulted in a significant increase in muscle strength, as determined by generation of specific force. Furthermore, Wnt7a reduced the level of contractile damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type toward slow-twitch in human primary myotubes. Taken together, our findings suggest that Wnt7a is a promising candidate for development as an ameliorative treatment for DMD.

Concepts: Energy, Muscle, Cardiac muscle, Electromyography, Muscular system, Muscular dystrophy, Atrophy, Muscle spindle