Article

Dietary Creatine Monohydrate Supplementation Increases Satellite Cell Mitotic Activity During Compensatory Hypertrophy

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Abstract

Nutritional status influences muscle growth and athletic performance, but little is known about the effect of nutritional supplements, such as creatine, on satellite cell mitotic activity. The purpose of this study was to examine the effect of oral creatine supplementation on muscle growth, compensatory hypertrophy, and satellite cell mitotic activity. Compensatory hypertrophy was induced in the rat plantaris muscle by removing the soleus and gastrocnemius muscles. Immediately following surgery, a group of six rats was provided with elevated levels of creatine monohydrate in their diet. Another group of six rats was maintained as a non-supplemented control group. Twelve days following surgery, all rats were implanted with mini-osmotic pumps containing the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label mitotically active satellite cells. Four weeks after the initial surgery the rats were killed, plantaris muscles were removed and weighed. Subsequently, BrdU-labeled and non-BrdU-labeled nuclei were identified on enzymatically isolated myofiber segments. Muscle mass and myofiber diameters were larger (P < 0.05) in the muscles that underwent compensatory hypertrophy compared to the control muscles, but there were no differences between muscles from creatine-supplemented and non-creatine-supplemented rats. Similarly, compensatory hypertrophy resulted in an increased (P < 0.05) number of BrdU-labeled myofiber nuclei, but creatine supplementation in combination with compensatory hypertrophy resulted in a higher (P < 0.05) number of BrdU-labeled myofiber nuclei compared to compensatory hypertrophy without creatine supplementation. Thus, creatine supplementation in combination with an increased functional load results in increased satellite cell mitotic activity.

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... Furthermore, a large body of evidence indicates that androgens and loading potentiates each other's effect on muscle growth. Load-induced hypertrophy involves edema, connective tissue proliferation, myogenic precursor cell proliferation, tissue repair, and inflammation [137][138][139][140]. These are all critical processes for the remodeling that results in overload-induced growth. ...
... Estrogen and testosterone can stimulate satellite cell activity [29, 142,143]. Myogenic regulatory factors (MRFs), including MyoD, myogenin, and cell cycle regulatory factors (CDK2, CDK4, and p21) regulate satellite cell activity and are induced in hypertrophying skeletal muscle [138,144]. Androgens can induce CDK2, CDK4, and p21 expression, while repressing the CDK inhibitor p16 in many cell types. Myogenin expression is also induced by androgen receptor expression in cultured muscle cells, suggesting that androgens may regulate myoblast differentiation. ...
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Estrogens and androgens influence the growth and maintenance of bones and muscles and are responsible for their sexual dimorphism. A decline in their circulating levels leads to loss of mass and functional integrity in both tissues. In the article, we highlight the similarities of the molecular and cellular mechanisms of action of sex steroids in the two tissues; the commonality of a critical role of mechanical forces on tissue mass and function; emerging evidence for an interplay between mechanical forces and hormonal and growth factor signals in both bones and muscles; as well as the current state of evidence for or against a cross-talk between muscles and bone. In addition, we review evidence for the parallels in the development of osteoporosis and sarcopenia with advancing age and the potential common mechanisms responsible for the age-dependent involution of these two tissues. Lastly, we discuss the striking difference in the availability of several drug therapies for the prevention and treatment of osteoporosis, as compared to none for sarcopenia.
... The authors demonstrated an increase in MRF4 protein concentration of only creatine group, in addition to narrow correlation with the increase in muscle fiber size. Studies with rats have shown that such factors are involved in the catabolic process and muscle anabolism (3,26,32,33). Similar results were found in two studies conducted by the group of Eijinde et al. (27,28). ...
... Another proposed mechanism discussed for increasing muscle mass is the concentration of intracellular water, responsible to enhance the cell hydration state. This effect may be related to increase protein synthesis, besides increases the expression of myogenic transcription factors (26,28,39,40). However, the mechanisms by which creatine exerts beneficial effects in the immobilization are poorly understood. ...
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Introduction: Recent studies point the creatine supplementation as promising therapeutic alternative in disorders of various types, especially myopathies and neurodegenerative disorder. Main: Purpose of this review is elucidated role of creatine on deleterious effect caused by limb immobilization in humans and rat. Methods: Analyzed articles were searched three online databases, PubMed, SportDicus e Scielo. After a review and analysis of the studies, were included in this review articles on effect of creatine supplementation on skeletal muscle in humans and rat, before, during and after a period of limb immobilization. Results: Studies analyzed showed positive points in use as a therapeutic tool in mitigating the deleterious effects of limb immobilization, in humans and rat. Conclusion: In short, the dataset although limiting presented by this literature review allows us to conclude that creatine supplementation can reduce muscle loss and / or assist in the recovery of muscle atrophy caused by immobilization and disuse in rats and humans. Still, we note that further research with better methodological rigor is needed to clarify the mechanisms by which creatine promotes the recovery of muscle atrophy. Moreover, these effects are positive and promising in the field of muscle rehabilitation, especially after the detention of members.
... The authors demonstrated an increase in MRF4 protein concentration of only creatine group, in addition to narrow correlation with the increase in muscle fiber size. Studies with rats have shown that such factors are involved in the catabolic process and muscle anabolism (3,26,32,33). Similar results were found in two studies conducted by the group of Eijinde et al. (27,28). ...
... Another proposed mechanism discussed for increasing muscle mass is the concentration of intracellular water, responsible to enhance the cell hydration state. This effect may be related to increase protein synthesis, besides increases the expression of myogenic transcription factors (26,28,39,40). However, the mechanisms by which creatine exerts beneficial effects in the immobilization are poorly understood. ...
Article
Full-text available
Introduction: Recent studies have pointing creatine supplementation as a promising therapeutic alterna- tive in several diseases, especially myopathies and neurodegenerative disorder. Objective: elucidate the role of creatine supplementation on deleterious effect caused by limb immobilization in humans and rats. Methods: Analyzed articles were searched by three online databases, PubMed, SportDicus e Scielo. After a review and analysis, the studies were included in this review articles on effect of creatine supplementation on skeletal muscle in humans and rat, before, during and after a period of limb immobilization. Results: Studies analyzed demonstrated positive points in use of creatine supplementation as a therapeutic tool to mitigating the deleterious effects of limb immobilization, in humans and rat. Conclusion: The dataset of this literature review allows us to conclude that creatine supplementation may reduce muscle loss and/or assist in the recovery of muscle atrophy caused by immobilization and disuse in rats and humans. Also, we note that further research with better methodological rigor is needed to clarify the mechanisms by which creatine support the recovery of muscle atrophy. Moreover, these effects are positive and promising in the field of muscle rehabilitation, especially after member’s immobilization.
... Additionally, Cr has been documented to induce the differentiation of satellite cells in culture (Vierck et al., 2003). Dietary addition of Cr could increase the number of satellite cells and result in higher satellite cell mitotic activity (SCMA) in skeletal muscles (Dangott et al., 2000;Olsen et al., 2006). Creatine pyruvate (CrPyr) is an organic compound that contains pyruvic acid and Cr at a ratio of 40:60 (Chen et al., 2011;Chen et al., 2012). ...
... The black dots represent nuclei staining positive for BrdU. The index of SCMA was calculated by dividing the number of BrdU-labeled nuclei by the total number of (BrdU-labeled + non-BrdU-labeled) nuclei (Dangott et al., 2000). ...
Article
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We investigated the effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on energy reserves, satellite cell mitotic activity (SCMA) and myogenic gene expression in breast muscle of embryos and neonatal broilers. A total of 960 eggs were randomly allocated into three treatments: 1) non-injected control group, 2) saline group injected with 0.6 mL of physiological saline (0.75%), and 3) CrPyr group injected with 0.6 mL of physiological saline (0.75%) containing 12 mg CrPyr/egg at 17.5 d of incubation. After hatching, a total of 120 male chicks were randomly assigned to each treatment group, with eight replicate sets per group. Selected chicks had body BW close to the average of their pooled group. Our results showed that the total and relative breast muscle weights of broilers subjected to CrPyr treatment were higher than those in the control and saline groups on 19 d of incubation (19 E), the day of hatch, 3 and 7 d post-hatch (P < 0.05). The myofiber diameter and cross-sectional area of individuals in the CrPyr group were higher than those in other treatments on 3 and 7 d post-hatch (P < 0.05). Moreover, IOF of CrPyr increased (P < 0.05) creatine concentrations on 19 E, the day of hatch and 3 d post-hatch, the same treatment increased phosphocreatine concentrations on 19 E. Broilers in the CrPyr group showed higher expression of myogenic differentiation 1 (MyoD) (P < 0.05), myogenin and paired box 7 (Pax7), as well as higher index of SCMA on 3 d post-hatch. However, myostatin mRNA expression in CrPyr-treated broilers was down-regulated on 3 d post-hatch (P < 0.05). These results indicated that IOF of CrPyr increased energy reserves of embryos and SCMA of broilers on 3 d post-hatch, which led to enhanced muscle growth in the late embryos and neonatal broilers. Additionally, IOF of CrPyr increased the activity of satellite cells possibly through up-regulating MyoD, myogenin, and Pax7 mRNA expression and down-regulating myostatin mRNA expression.
... Estes resultados indicam que a creatina foi eficiente em reduzir a PL após exercícios exaustivos. Em outro estudo foi demonstrado que a suplementação de creatina aumentou a atividade mitótica de células satélites durante a indução de hipertrofia compensatória muscular, o que aumenta a capacidade de regeneração celular (DANGOTT; SCHULTZ;MOZDZIAK, 2000). ...
... Estes resultados indicam que a creatina foi eficiente em reduzir a PL após exercícios exaustivos. Em outro estudo foi demonstrado que a suplementação de creatina aumentou a atividade mitótica de células satélites durante a indução de hipertrofia compensatória muscular, o que aumenta a capacidade de regeneração celular (DANGOTT; SCHULTZ;MOZDZIAK, 2000). ...
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Physical exercises associated with a balanced diet are important factors for health promotion. However intense and prolonged or strenuous exercise may promote chronic infam-mation, overtraining and increased susceptibility to infections. Being cause or consequence, one of the factors that contribute to deleterious effects is exacerbated increase in the synthesis of pro-oxidant compounds, known as reactive oxygen species (ROS) and nitrogen species (RNS). The increase of ROS and RNS may reduce the body antioxidant capability, a condition known as oxidative stress. Oxidative stress has been implicated as a promoter of injuries to various cellular constituents, especially on the membranes, an effect known as lipid peroxidation. To attenuate the effects of ROS and RNS, the body has the antioxidant defense system, located in different cellular compartments and with different functions. Studies have increasingly shown that the antioxidant system can be infuenced by specific nutritional interventions, among which are included vitamins, minerals, favonoids and amino acids. Considering the fact that thousands of people engage in the practice of physical exercise every day, and that many of them go beyond their limits, this review aims to address the major sites of synthesis of ROS during exercise and nutrition strategies and their possible mechanisms action on the antioxidant defense system.
... In addition, improvements in repeated sprint performance, bench press strength, fatigue resistance, body weight, and relative lifting volume can be observed within a relatively short period of time [77]. Moreover, creatine supplementation has been demonstrated to increase the activation of satellite cells and myonuclei in muscle following chronic resistance training [78], and long-term studies have observed that those supplementing with creatine can experience beneficial body composition adaptations [76]. b-Alanine supplementation has been demonstrated to augment muscle carnosine concentrations in humans [79][80][81]. ...
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Many sports involve repeated bouts of high-intensity exercise. High-intensity exercise is compromised, however, by the early onset of exercise-induced fatigue. Metabolic by-products, ion dysbalance and amount of phosphocreatine are considered the main peripheral causes of fatigue during high-intensity exercise. Intake of nutritional ergogenic aids is commonplace to enhance performance of high-intensity exercise by offsetting the potential mechanisms of fatigue. Creatine, probably one of the best known nutritional aids to enhance performance of high-intensity exercise, has convincingly substantiated its ergogenic potential. Although multi-ingredient supplements are now common, the justification for effectiveness is mostly based on observations with single intake of those ingredients. In this narrative review, the main focus is on the evidence of the effect of co-ingestion of ergogenic aids on performance of high intensity exercise for which the single intake has shown beneficial effects on high-intensity performance.
... Absorption process of amino acids in intestine especially lysine is more efficient at the early age of chicken than in later and finisher phase of chicken.The efficiency of enzyme absorption activity in chicken will decrease after three weeks [1]. Early nutrition in the early age of chicken is positively correlated to growth rate [2,3]. That delayed feeding will deteriorate broiler performance was confirmed in many researches. ...
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This study was performed to study pectoralis muscle development in Jawa Super chicks in conjunction with local starter feed effect during the early post hatch period. Twenty Jawa Super day old chicks (DOC) were fed standard starter diet containing 20-21% crude protein during the experimental period. The chicks were divided into four groups consisted of five DOCs. The first group was starved for the first 3 days before continued with commercial diet until seventh days old. The second group was fed with standard chick starter commercial diet from post hatch until seventh days old, third group was fed with Formula 3 (F3) from posthatch until seventh days old and the forth group was fed with Formula 4 (F4) from posthatch until seventh days old. The parameters measured were body weight, pectoralis thoracicus weight, pectoralis thoracicus area, and cross-sectional area of the myofibers. Data gathered were statistically analyzed using one-way ANOVA, followed by Tukey Tests. The results showed that groups 1 and 4 had lower body weight, pectoralis thoracicus weight, pectoralis thoracicus area and cross-sectional myofiber area compared to group 2 and 3 (P≤0.05). The results of the current study suggested that early posthatch local feed F3 in Jawa Super chicks was important to body weight and pectoralis muscle development. The substitution of local feed F4 in early posthatch was not significant for pectoralis muscle development compared to standard chick starter commercial and F3 diet.
... Thus, it is not surprising that early chick nutrition has been shown to have a positive effect on the satellite cells activity and posthatch muscle growth (e.g. Dangott et al., 2000;Batal and Parsons, 2002;Halvey et al., 2003;Henderson et al., 2008). Uni et al. (2005) showed that administration of exogenous nutrients such as carbohydrate and β-hydroxyβ-methylbutyrate into the amnion of broiler embryos at 17-18 d of embryonic development replenished liver glycogen stores that can be depleted during the prenatal period. ...
Article
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Studies were conducted using a commercial Inovoject(TM) system to determine effects of in ovo feeding of dextrin and iodinated casein (IC) on hatch and posthatch growth in broilers. At ∼18.5 d embryonic development, eggs were treated with 0, 240, or 480 μg IC/mL in saline (Cont, IC240, and IC480) or dextrin (Dext, DextIC240 and DextIC480). The Dext solution consisted of 18% maltodextrin and 10% potato starch dextrin; saline was the vehicle used by the company for in ovo vaccination. The volume for all in ovo treatments was 50 μL/injection. Eggs in Experiment 1 were transferred to a commercial hatcher unit whereas eggs in Experiments 2 and 3 were transferred to a research hatcher unit to assess effects of treatments on timing of hatch. At hatch, chicks were randomly selected and placed in floor pens and grown to 6 wk. In Experiment 1, there were no differences in hatch weights, but broilers provided Dext IC240 in ovo were heavier (P < 0.05) at 6 wk compared to other treatments with the exception of the Dext IC240 group. In Experiment 2, hatch weights were heavier (P < 0.05) in chicks receiving IC240 and DexIC480 treatments compared to Controls. At 6 wk, broilers in all treatments were heavier (P < 0.05) than Cont with the exception of IC480. In Experiment 3, hatch was stimulated by IC240 (in saline), but was delayed by Dext IC240. Serum analysis of β-hydroxybutyrate (μM/mL), as an indicator of ketone accumulation from fat metabolism of chicks held in chick boxes for 24 h posthatch (to simulate delay in placement after hatch), indicated that chicks in the IC240 group (that hatched earlier) had higher blood ketones compared to chicks that received Dext or DextIC240 in ovo (that hatched later). We conclude dextrin and iodinated casein (240 μg/mL) provided in ovo (∼18.5 d of embryonic development) has the potential to improve chick quality and posthatch body weight by delaying or narrowing hatch window.
... Antes y durante la fusión ocurre una extensiva reorganización citoesquelética donde los ensamblajes dinámicos que regulan la fusión celular son dependientes de la hidrólisis de ATP, si bien la polimerización y disociación de los monómeros de actina puede requerir hasta el 50% del gasto energético celular ( Olsen et al. (2006) mostró que la suplementación con Cr (6 g Cr + 14 g CHO día-1) en sujetos que realizan un protocolo de entrenamiento de resistencia (16 semanas) aumenta la proporción de células satélite con respecto al grupo placebo, además de incrementar el número de mionúcleos por fibra. Dangott et al. (2000) ya había reportado un incremento en la actividad mitótica de las células satélite en el músculo esquelético de ratón tras un periodo de suplementación con Cr. ...
... On the other hand, creatine monohydrate (CrM) has long been used as an oral supplement to enhance muscular strength [16] and hypertrophic adaptations [17] when ingested during resistance training periods. A number of mechanisms have been proposed to explain the benefit that CrM has on resistance traininginduced adaptations, including larger lean body mass [18], increased protein expression and synthesis [19], changes in myogenic transcription factors [20], and elevated mitotic activity of satellite cells [21]. Above all, the most likely benefit appears to be due to improved performance during resistance training sessions by increasing intra-muscular phosphocreatine stores, thereby allowing a greater work capacity and thus training stimuli for enhanced chronic training adaptation [22,23]. ...
Article
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Background Several studies have examined the effect of creatine monohydrate (CrM) on indirect muscle damage markers and muscle performance, although pooled data from several studies indicate that the benefits of CrM on recovery dynamics are limited. Objective This systematic review and meta-analysis determined whether the ergogenic effects of CrM ameliorated markers of muscle damage and performance following muscle-damaging exercises. Methods In total, 23 studies were included, consisting of 240 participants in the CrM group (age 23.9 ± 10.4 years, height 178 ± 5 cm, body mass 76.9 ± 7.6 kg, females 10.4%) and 229 participants in the placebo group (age 23.7 ± 8.5 years, height 177 ± 5 cm, body mass 77.0 ± 6.6 kg, females 10.0%). These studies were rated as fair to excellent following the PEDro scale. The outcome measures were compared between the CrM and placebo groups at 24–36 h and 48–90 h following muscle-damaging exercises, using standardised mean differences (SMDs) and associated p -values via forest plots. Furthermore, sub-group analyses were conducted by separating studies into those that examined the effects of CrM as an acute training response (i.e., after one muscle-damaging exercise bout) and those that examined the chronic training response (i.e., examining the acute response after the last training session following several weeks of training). Results According to the meta-analysis, the CrM group exhibited significantly lower indirect muscle damage markers (i.e., creatine kinase, lactate dehydrogenase, and/or myoglobin) at 48–90 h post-exercise for the acute training response (SMD − 1.09; p = 0.03). However, indirect muscle damage markers were significantly greater in the CrM group at 24 h post-exercise (SMD 0.95; p = 0.04) for the chronic training response. Although not significant, a large difference in indirect muscle damage markers was also found at 48 h post-exercise (SMD 1.24) for the chronic training response. The CrM group also showed lower inflammation for the acute training response at 24–36 h post-exercise and 48–90 h post-exercise with a large effect size (SMD − 1.38 ≤ d ≤ − 1.79). Similarly, the oxidative stress markers were lower for the acute training response in the CrM group at 24–36 h post-exercise and 90 h post-exercise, with a large effect size (SMD − 1.37 and − 1.36, respectively). For delayed-onset muscle soreness (DOMS), the measures were lower for the CrM group at 24 h post-exercise with a moderate effect size (SMD − 0.66) as an acute training response. However, the inter-group differences for inflammation, oxidative stress, and DOMS were not statistically significant ( p > 0.05). Conclusion Overall, our meta-analysis demonstrated a paradoxical effect of CrM supplementation post-exercise, where CrM appears to minimise exercise-induced muscle damage as an acute training response, although this trend is reversed as a chronic training response. Thus, CrM may be effective in reducing the level of exercise-induced muscle damage following a single bout of strenuous exercises, although training-induced stress could be exacerbated following long-term supplementation of CrM. Although long-term usage of CrM is known to enhance training adaptations, whether the increased level of exercise-induced muscle damage as a chronic training response may provide potential mechanisms to enhance chronic training adaptations with CrM supplementation remains to be confirmed.
... Intracellular hydration is a potential factor that may contribute to greater muscle hypertrophy by stimulating pathways that increase protein synthesis and those that diminish protein degradation (Schoenfeld, 2012(Schoenfeld, , 2013. It has been theorized that the stimulus associated with cell hydration status may trigger proliferation of satellite cells and facilitate their fusion to induce myofiber hypertrophy (Dangott et al., 2000). Moreover, acute changes in body proteins occur mainly in the cellular compartment (Matthie, 2008) and changes in body proteins are generally accompanied by changes in ICF (Matthie, 2008). ...
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Phase angle (PhA) is an angular-derived bioelectrical impedance parameter based on resistance and reactance that has been widely used in different populations as an objective indicator of cellular health. The purpose of this study was to analyze the effect of resistance training (RT) on PhA in older women. Forty-one older women (67.2 ± 4.5 years, 64.0 ± 12.3 kg, 154.7 ± 5.2 cm, and 26.6 ± 4.8 kg/m(2) ) were randomly assigned to one of two groups: a training group (TG, n = 19) that underwent progressive RT for 12 weeks (eight exercises, three sets of 10-15 repetitions maximum, three times per week) or a control group (CG, n = 22) that did not perform any type of exercise during the intervention period. Resistance, reactance, PhA, total body water (TBW), intracellular (ICW) and extracellular (ECW) water were assessed by spectral bioelectrical impedance. There was a significant group by time interaction (P < 0.05) for PhA, TBW, and ICW in which only the TG increased their scores after the intervention period (PhA = +6.5%, TBW = +2.8%, and ICW = +5.1%). The results suggest that progressive RT promotes an increase in PhA in older women. Therefore, the PhA seems to be a good parameter to assess changes in cellular health during RT intervention.
... Intracellular hydration may contribute to muscle hypertrophy by stimulating pathways that increase protein synthesis as well as those that diminish protein degradation [33,34]. Moreover, it has been theorized that the stimulus associated with cell hydration status may trigger proliferation of satellite cells and facilitate their fusion to hypertrophying myofibers [8]. Increasing SMM is a primary goal of many recreational individuals of both sexes who are engaged in RT programs. ...
Article
The main purpose of the present study was to investigate the effect of a hypertrophy-type resistance training protocol on phase angle, an indicator of cellular integrity, in young adult men and women. Twenty-eight men (22.2 ± 4.3 years, 67.8 ± 9.0 kg and 174.2 ± 6.8 cm) and 31 women (23.2 ± 4.1 years, 58.7 ± 12.1 kg and 162.7 ± 6.4 cm) underwent a progressive RT for 16 weeks (2 phases, 8 weeks each), 3 times per week, consisting of 10 to 12 whole body exercises with 3 sets of 8-12 repetitions maximum. Phase angle, resistance, reactance, and total body water (intra and extracellular water compartments) were assessed by bioimpedance spectroscopy (Xitron 4200 Bioimpedance Spectrum Analyzer). Total body water, intracellular water, and phase angle increased significantly (P < 0.05) in men (7.8%, 8.3%, and 4.3%, respectively) and women (7.6%, 11.7%, and 5.8% respectively), with no significant difference between sexes (P > 0.05). Bioimpedance resistance decreased (P < 0.05) similarly in both sex (men = -4.8%, women = -3.8%). The results suggest that regardless of sex, progressive RT induces an increase in phase angle and a rise in cellular hydration.
... In addition, improvements in repeated sprint performance, bench press strength, fatigue resistance, body weight, and relative lifting volume can be observed within a relatively short period of time [77]. Moreover, creatine supplementation has been demonstrated to increase the activation of satellite cells and myonuclei in muscle following chronic resistance training [78], and long-term studies have observed that those supplementing with creatine can experience beneficial body composition adaptations [76]. b-Alanine supplementation has been demonstrated to augment muscle carnosine concentrations in humans [79][80][81]. ...
... In agreement with these findings, an in vitro study revealed that creatine induced differentiation of myogenic satellite cells (Vierck et al. 2003). These data were corroborated by a subsequent experimental study in which creatine supplementation enhanced satellite cell mitotic activity following compensatory hypertrophy, which was induced in rat plantaris muscle by removing the soleus and gastrocnemius muscles (Dangott et al. 2000). Importantly, findings from a human study demonstrated that 16 weeks of creatine supplementation in combination with resistance training amplified the training-induced increase in satellite cell number and myonuclei concentration in skeletal muscle fibers, which could allow for enhanced muscle fiber growth in response to strength training as typically seen after creatine intake (Olsen et al. 2006). ...
Article
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This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.
... In addition, improvements in repeated sprint performance, bench press strength, fatigue resistance, body weight, and relative lifting volume can be observed within a relatively short period of time [77]. Moreover, creatine supplementation has been demonstrated to increase the activation of satellite cells and myonuclei in muscle following chronic resistance training [78], and long-term studies have observed that those supplementing with creatine can experience beneficial body composition adaptations [76]. b-Alanine supplementation has been demonstrated to augment muscle carnosine concentrations in humans [79][80][81]. ...
... By combining low-load RT to failure with short-rest intervals, even further improved metabolic stress might trigger large anabolic effects (Schoenfeld, 2013). Indeed, RT with high levels of metabolic stress has been shown to elevate hormonal levels (Goto et al., 2005), muscle fibre recruitment and cell swelling (Schoenfeld, 2013), ultimately leading to increased protein synthesis and satellite cell activation (Griggs et al., 1989;Lang et al., 1998;Dangott et al., 2000;Sinha-Hikim et al., 2003). In our study, the marked elevations in GH immediately post-RT in the SL group point to a greater metabolic stress in the SL protocol as compared to the LH protocol. ...
Article
We investigated the effects of volume-matched resistance training (RT) with different training loads and rest intervals on acute responses and long-term muscle and strength gains. Ten subjects trained with short rest (30 s) combined with low load (20 RM) (SL) and ten subjects performed the same protocol with long rest (3 min) and high load (8 RM) (LH). Cross-sectional area (CSA) of the upper arm was measured by magnetic resonance imaging before and after 8 weeks of training. Acute stress markers such as growth hormone (GH) and muscle thickness (MT) changes have been assessed pre and post a single RT session. Only the SL group demonstrated significant increases in GH (7704·20 ± 11833·49%, P<0·05) and MT (35·2 ± 16·9%, P<0·05) immediately after training. After 8 weeks, the arm CSA s in both groups significantly increased [SL: 9·93 ± 4·86% (P<0·001), LH: 4·73 ± 3·01% (P<0·05)]. No significant correlation between acute GH elevations and CSA increases could be observed. We conclude that short rest combined with low-load training might induce a high amount of metabolic stress ultimately leading to improved muscle hypertrophy while long rest with high-load training might lead to superior strength increases. Acute GH increases seem not to be directly correlated with muscle hypertrophy.
... Supplementation of Cr can improve myocardial energy and performance in patients with heart diseases [7,8]. This suggests that an increase in intracellular Cr levels may increase the myocardial energy reserve via the creatine kinase (CK) system [9] and a specific Cr transporter (CrT) [10]. ...
Article
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Creatine phosphate (Cr) and its phophorylated form (phosphocreatine, PCr) is catalyzed by creatine kinase (CK) reaction to phosphorylate ADP to ATP, which plays an important role in muscle energetics. This study aims to examine the combined effect of Cr and/or exercise training on myocardial energy reservation, using female hamsters. Fifty female Golden Syrian hamsters were divided into 4 groups of control (n=10), Cr supplementation (Cr+; n=10), exercise training (Ex; n=10), and Cr supplementation combined with exercise training (Cr+Ex; n=10). In the exercise-trained group, wheel-running for exercise (10 min. a day, 5 days a week) was imposed for 2 weeks. All animals were measured for exercise metabolic rate (EMR) on the 1 st , 7 th and 14 th day. After the animals were sacrificed, the hearts were cut and weighed and the contents of Cr, PCr, total Cr (TCr), CK activities and RNA content were measured, using a spectrophotometric method. The animals treated with Cr+Ex on the 2 nd week yielded the greatest EMR level with the lowest of oxygen consumption, compared with Cr+ or ex alone. Additionally, all parameters regulating myocardial energy reservation (contents of Cr, PCr, TCr and CK activity) and RNA contents improved greatly in Cr+Ex, treatment. These data indicate that creatine supplementation, when combined with exercise training, have many benefits for oxygen economy and effectiveness for myocardial energy reservation via Cr metabolism.
... Other studies in failing hearts of humans and animals demonstrated a reduction in the creatine kinase (CK) system [5] and its products, Cr and phosphocreatine (PCr) contents [6]. Supplementation of Cr can improve myocardial energy and performance in patients with heart diseases [7, 8]. This suggests that an increase in intracellular Cr levels may increase the myocardial energy reserve via the creatine kinase (CK) system [9] and a specific Cr transporter (CrT) [10]. ...
... Other studies in failing hearts of humans and animals demonstrated a reduction in the creatine kinase (CK) system [5] and its products, Cr and phosphocreatine (PCr) contents [6]. Supplementation of Cr can improve myocardial energy and performance in patients with heart diseases [7, 8]. This suggests that an increase in intracellular Cr levels may increase the myocardial energy reserve via the creatine kinase (CK) system [9] and a specific Cr transporter (CrT) [10]. ...
... Other studies in failing hearts of humans and animals demonstrated a reduction in the creatine kinase (CK) system [5] and its products, Cr and phosphocreatine (PCr) contents [6]. Supplementation of Cr can improve myocardial energy and performance in patients with heart diseases [7, 8]. This suggests that an increase in intracellular Cr levels may increase the myocardial energy reserve via the creatine kinase (CK) system [9] and a specific Cr transporter (CrT) [10]. ...
... Other studies in failing hearts of humans and animals demonstrated a reduction in the creatine kinase (CK) system [5] and its products, Cr and phosphocreatine (PCr) contents [6]. Supplementation of Cr can improve myocardial energy and performance in patients with heart diseases [7, 8]. This suggests that an increase in intracellular Cr levels may increase the myocardial energy reserve via the creatine kinase (CK) system [9] and a specific Cr transporter (CrT) [10]. ...
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Background: Menopause in elder women may induce various dysfunctions in the cardiovascular system. Previous studies show that creatine (Cr) supplementation, estrogen (E 2) replacement, or exercise training are effective for cardiac performance. Objective: To examine the combined effect of Cr and/or E 2 with exercise training on myocardial energy reservation, using ovariectomized female hamsters. Materials and methods: Female Golden Syrian hamsters were used for this study. A hundred ovariectomized hamsters were divided into no-exercise and exercise-trained groups, in which each group was separated into control (n=10), Cr depletion (Cr-; n=10), Cr supplementation (Cr+; n=10), E 2 replacement (E 2; n=10) and Cr supplementation combined with E 2 replacement (Cr+E 2 ; n=10). In the exercise-trained group, wheel-running exercise (10 min. a day, 5 days a week) was imposed for 9 weeks, and the exercise metabolic rate (EMR) was measured. After the animals were sacrificed, the right ventricles were cut and weighed, which were rapidly frozen in liquid nitrogen for storage at-70 o C. The contents of Cr, phosphocreatine (PCr), total Cr (TCr) and creatine kinase (CK) activities were measured, using the spectrophotometric method. Creatine transporter protein (CrT) was measured by Western blotting. Results: Cr+ or E 2 combined with exercise training yielded greater accumulation of all myocardial metabolic phosphate contents, CK activity and CrT protein than Cr+ or E 2 alone. All parameters regulating myocardial Cr metabolism were improved greatly in Cr+ plus E 2 combined with exercise training. Conclusion: Creatine supplementation and estrogen replacement, when combined with exercise training, become more effective for myocardial energy reservation via in estrogen-deficient hamsters.
... Precisely timed protein supplementation after resistance exercise is thought to increase the availability of intracellular amino acids, which promote an acute increase in net protein balance that is utilised by growing myofibres (for a review, see Gibala 2000). Creatine supplementation augments the muscle hypertrophy response by eliciting larger increases in fibre cross-sectional area compared to training alone; chiefly by enhancing satellite cell activity and the production of MRFs (Dangott et al. 2000;Olsen et al. 2006). ...
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Satellite cells are muscle-specific progenitor cells involved in the routine maintenance of skeletal muscle homeostasis, growth and regeneration. They are activated by various stimuli (myotrauma, growth factors etc), undergo rounds of proliferation as skeletal muscle myoblasts, to differentiate and fuse with each other to generate new myotubes or onto existing myofibres to augment growth or repair damaged fibres. Satellite cells contribute to hypertrophy by facilitating nuclear addition, which maintains contractile protein synthetic capacity. Conversely, during atrophy the dysregulation of satellite cells (e.g., via myogenic suppression), causes an opposing deficit in nuclear supplementation/contractile protein synthesis. The ‘activity status’ of satellite cells, an important determinant of muscle regenerative capacity is not routinely addressed in studies characterising mechanisms of muscle hypertrophy and atrophy. Therefore, the investigations described within this thesis examined the satellite cell specific signalling events that contribute to muscle loss or gain, in rodent models experiencing non-mechanically-induced muscle hypertrophy or atrophy. Chronic administration of an anabolic agent (BRL-47672, the pro-drug of clenbuterol) increased the expression of early components of satellite cell myogenesis (pax7, ki-67, myoD) but caused no alteration in myogenin expression, relative to control in rat soleus muscle. Pro-drug administration increased myostatin expression, with no concomitant change in follistation mRNA; this is likely a compensatory mechanism to check excessive muscle growth. These results provided evidence of increase satellite cell activity in hypertrophying muscle. In a lipopolysaccharide (LPS)-infusion model of muscle atrophy, satellite cells were inhibited in an inflammatory-dependent manner. LPS infusion caused early (<2hr) elevations inflammatory cytokines TNF-, IL-6 and NF-B. LPS-induced elevation in cytokine transcript levels paralleled increased myostatin and decreased pax7 and myoD mRNA and protein expression. The differential increase in cytokines also paralleled the reduction in the number of pax7+ and myoD+ satellite cells. These results suggest that alterations in satellite cell activity may contribute to the progression of muscle atrophy, due to the suppression of muscle compensatory mechanisms, which include satellite cell activation, differentiation and fusion for nuclear supplementation. Co-infusion with an anti-inflammatory agent, dexamethasone (Dex), blunted LPS-induced increase in inflammatory cytokines but had an additive effect on myogenic suppression. Dex+LPS infusion prevented LPS-induced increase in myogenin and resulted in an additional suppression of pax7 and myoD, greater than that elicited by either substance alone. Negative regulation of satellite cells by glucocorticoids could impede their efficacy in the treatment of inflammatory muscle disorders. The research within this thesis emphasise satellites are important for maintenance of muscle homeostasis and their activation/inhibition, may determine the magnitude of muscle loss or gain. This was demonstrated by the pattern of pax7 and myoD expression in hypertrophying muscle, where both markers were up-regulated and in atrophying muscle, where they were down-regulated. Down-regulation of these markers in atrophy could have implications for muscle regenerative capacity, especially myoD, whose expression was continuously inhibited across all time-points sampled in septic muscles. Satellite cells are a major source of compensatory action in skeletal muscle, their activation and subsequent myogenesis represents an auxiliary mechanism by which muscle responds to damaging stimuli; therefore their dysregulation (through the alteration of key myogenic markers) results in an alteration of normal function. Such dysregulation, as frequently reported in cases or progressive muscle degeneration and sarcopenia, limits the efficacy of muscle compensatory processes (i.e. satellite cell activation/proliferative or differentiation potential), thereby contributing to the progression of muscle atrophy and myopathy
... Estudios en humanos han reportado que el entrenamiento de resistencia incrementa la proporción de células satélite y el número de mionúcleos en los músculos entrenados lo cual sugiere que el entrenamiento induce la activación de este tipo de células como un mecanismo adaptivo durante la hipertrofia muscular; de acuerdo con esto, el trabajo de Olsen et al. (2006) mostró que la suplementación con Cr (6 g Cr + 14 g CHO día-1) en sujetos que realizan un protocolo de entrenamiento de resistencia (16 semanas) aumenta la proporción de células satélite con respecto al grupo placebo, además de incrementar el número de mionúcleos por fibra. Dangott et al. (2000) ya había reportado un incremento en la actividad mitótica de las células satélite en el músculo esquelético de ratón tras un periodo de suplementación con Cr. ...
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Desde hace más de 30 años, la suplementación con creatina (Cr) y la descripción de sus efectos sobre el rendimiento deportivo a corto y largo plazo se han convertido en el principal objeto de estudio de muchos investigadores. No obstante, en los últimos años el problema de investigación en el campo del uso de suplementos ergogénicos ha cambiado al punto de pretender explicar los mecanismos metabólicos por los cuales la administración de Cr incrementa algunas capacidades metabólicas que favorecen la ejecución de ciertos deportes o simplemente benefician la adaptación muscular. El propósito de esta revisión es analizar los principales fundamentos metabólicos que explican los efectos de la ingesta de Cr durante el ejercicio, enfatizando en entrenamiento de resistencia. Los mecanismos principales que sustentan estos efectos involucran principalmente la mayor biodisponibilidad energética de Cr optimizando la acción buffer espacial/temporal que ofrece el sistema Cr/PCr/CK, que conlleva a un mayor rendimiento de ATPasas miocelulares, incremento en la resíntesis de PCr, reducción en la acumulación de Pi, Ca2+, H+ y ADP, mayor disponibilidad de aminoácidos, inhibición de glucólisis y un posible aumento del rendimiento neuromuscular. Asimismo, un incremento en los procesos de proliferación y diferenciación de células musculares evaluados por la activación de cascadas de señalización y el aumento en la expresión de proteínas implicadas en estos procesos (IGF-I/PI3K/Akt, SPHK1/MAPK/p38/MEF-2/MRFs, posiblemente mTOR, MHC, CK, Ca2+-ATPasa del retículo sarcoplasmático, polimerización de actina y fusión de mioblastos) y la inactivación y/o reducción en la expresión de proteínas con funciones ergolíticas (GSK3β, miostatina y posiblemente AMPK) explican bioquímicamente los efectos que tiene el monohidrato de Cr sobre el rendimiento deportivo. Así, el monohidrato de Cr parece ser el suplemento nutricional más efectivo y seguro para aumentar la masa muscular, la fuerza, la resistencia a la fatiga y el rendimiento en ejercicios de alta intensidad, entre muchos otros efectos positivos sobre la salud. Palabras clave: Sistema Cr/PCr/CK, Monohidrato de Creatina, Suplemento Ergogénico, Metabolismo Energético Miocelular, Ejercicio de Resistencia, Cascada de Señalización Bonilla DA. PubliCE 2013
... Atividades intensas, especialmente as excêntricas estão associadas à lesão muscular [2] e a lesão associa-se a exaustão do músculo, prejudicando a função contrátil pela resposta infl amatória. ...
Article
Com o objetivo de avaliar o impacto do teste de exaustão (TE), com exercícios resistidos em três grupamentos musculares distintos, sobre a magnitude das alterações sanguíneas de atletas, foram estudados 12 indivíduos (23 ± 4 anos) do sexo masculino (79 ± 10kg), atletas de musculação e voluntários ao estudo. Após 4 semanas de treinamento e dieta ajustada para 1,5g/kg/dia e 30 kcal/g prot., foi aplicado o TE que iniciava com 80% de 1 RM e redução de 20% até a fadiga (não execução da repetição). O TE foi realizado para: 1) supino reto; 2) agachamento na máquina Hack®; 3) remada baixa no pulley, sem descanso entre os exercícios. Foram realizadas coletas de sangue, antes e após a realização dos três TE, para dosagens hemogasimétricas e bioquímicas. Após o TE, aumentaram as atividades das enzimas (U/L) creatino-quinase (CK), creatino-quinase isoenzima cardíaca (CK-MB), lactato desidrogenase (LDH), alanina aminotransferase (ALT), aspartato aminotransferase (AST) e os valores de glicose, Ca+, Na+ , PO2, hematócrito, osmolalidade. Por outro lado, houve redução significativa do pH, HCO3 e pCO2 e variação não significativa do ácido úrico. Não houve correlação do teste de RM com o somatório das repetições no TE. Os indicadores isolados mais sensíveis ao volume de exercícios foram a PCO2 e a AST que predizem até 50% e 40% das repetições, respectivamente. A associação da PCO2, pressão parcial de oxigênio (PO2), hematócrito (Ht), creatina quinase porção cérebro-músculo (CK-MB) e bicarbonato (HCO3), têm o nível preditivo máximo de aproximadamente 92%. O teste exaustivo dos 3 grupamentos musculares leva a alterações sanguíneas indicativas de estresse metabólico em que variações de pO2, pCO2, HCO3-, Ht, e CKMB predizem 92% do esforço dispendido no TE.Palavras-chave: marcadores bioquímicos, teste de exaustão, grupos musculares.
... NO precursors are popular supplements among those engaged in resistance exercise due to the notion that improved blood flow to both Type I and Type II muscle fibers may not only enhance acute performance, but also improve nutrient delivery to promote recovery and further stimulate hypertrophic responses. Enhanced blood flow to the exercising or recovering musculature may promote cellular swelling, which is believed to be an advantageous hypertrophic response due to various mechanisms (Cholewa et al. 2019), including stimulation of satellite cell proliferation (Dangott et al. 2000). Yet, data regarding the effects of dietary NO 3 or other NO precursors on muscle blood flow in active individuals is somewhat inconsistent. ...
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Purpose To determine the effects of dietary nitrate supplementation, in the form of red spinach extract (RSE), on adaptations to offseason training in collegiate athletes. Methods: Sixteen Division I male baseball athletes (20.5 ± 1.7y, 90.4 ± 0.5 kg) enrolled in this study and were randomized into a RSE (n = 8) or placebo (n = 8; PL) group. Athletes completed an 11-week resistance training program during the offseason, which consisted of 2-3 workouts per week of upper and lower-body exercises and baseball-specific training. Athletes consumed a RSE (2 g; 180 mg nitrate) or PL supplement daily for the entire offseason training program. Pre and post-training, all athletes underwent one-repetition maximum (1RM) strength testing for the bench press and completed a Wingate anaerobic cycle test (WAnT). Body composition analysis was completed via a 4-compartment model, as well as muscle thickness (MT) measurement of the rectus femoris (RF) and vastus lateralis (VL) via ultrasonography. Resting heart rate and blood pressure (BP) were also obtained. Separate repeated measures analyses of variance were used to analyze all data. Results: Significant (p ≤ 0.05) main effects for time were observed for improved bench 1RM, fat-free mass, body fat percentage, RF MT, and VL MT. No significant group x time interactions (p > 0.05) were found for any measure of performance, body composition, or cardiovascular health. However, a trend for improved peak power in the WAnT was observed (p = 0.095; η²=0.200). Conclusions: These data suggest that daily RSE supplementation had no effect on performance, body composition, or cardiovascular measures in male Division I baseball players following offseason training.
... 57 Although the exact mechanisms by which CrM may benefit the immobilized muscle have not been established, some evidence suggests it is the result of an upregulation of myogenic transcription factors (myogenin) 57,58 and satellite cell activity. 59,60 Additional data 61 indicated that CrM may serve as a potential strategy for enhancing bone remodeling by stimulating cell growth, differentiation, and mineralization, which would be beneficial for skeletal injuries. ...
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Nutritional interventions are not commonly a standard of care in rehabilitation interventions. A nutritional approach has the potential to be a low-cost, high-volume strategy that complements the existing standard of care. In this commentary, our aim is to provide an evidence-based, practical guide for athletes with injuries treated surgically or conservatively, along with healing and rehabilitation considerations. Injuries are a normal and expected part of exercise participation. Regardless of severity, an injury typically results in the athlete's short- or long-term removal from participation. Nutritional interventions may augment the recovery process and support optimal healing; therefore, incorporating nutritional strategies is important at each stage of the healing process. Preoperative nutrition and nutritional demands during rehabilitation are key factors to consider. The physiological response to wounds, immobilization, and traumatic brain injuries may be improved by optimizing macronutrient composition, caloric consumption, and nutrient timing and using select dietary supplements. Previous research supports practical nutrition recommendations to reduce surgical complications, minimize deficits after immobilization, and maximize the chance of safe return to play. These recommendations include identifying the individual's caloric requirements to ensure that energy needs are being met. A higher protein intake, with special attention to evenly distributed consumption throughout the day, will help to minimize loss of muscle and strength during immobilization. Dietary-supplement strategies may be useful when navigating the challenges of appropriate caloric intake and timing and a reduced appetite. The rehabilitation process also requires a strong nutritional plan to enhance recovery from injury. Athletic trainers, physical therapists, and other health care professionals should provide basic nutritional recommendations during rehabilitation, discuss the timing of meals with respect to therapy, and refer the patient to a registered dietitian if warranted. Because nutrition plays an essential role in injury recovery and rehabilitation, nutritional interventions should become a component of standard-of-care practice after injury. In this article, we address best practices for implementing nutritional strategies among patients with athletic injuries.
... 11 It has been suggested that CR supplementation alone is limited in its effect on satellite cell mitotic activity and that CR supplementation needs to be combined with exercise to promote muscular hypertrophy. 66 However, the underlying mechanisms of CR remain unknown, 67 highlighting the need for additional investigations. ...
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Context: Nutritional interventions stimulate muscle protein synthesis in older adults. To optimize muscle mass preservation and gains, several factors, including type, dose, frequency, timing, duration, and adherence have to be considered. Objective: This systematic review and meta-analysis aimed to summarize these factors influencing the efficacy of nutritional interventions on muscle mass in older adults. Data sources: A systematic search was performed using the electronic databases MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and SPORTDiscus from inception date to November 22, 2017, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included randomized controlled trials, mean or median age ≥65 years, and reporting muscle mass at baseline and postintervention. Exclusion criteria included genetically inherited diseases, anabolic drugs or hormone therapies, neuromuscular electrical stimulation, chronic kidney disease, kidney failure, neuromuscular disorders, and cancer. Data extraction: Extracted data included study characteristics (ie, population, sample size, age, sex), muscle mass measurements (ie, method, measure, unit), effect of the intervention vs the control group, and nutritional intervention factors (ie, type, composition, dose, duration, frequency, timing, and adherence). Data analysis: Standardized mean differences and 95%CIs were calculated from baseline to postintervention. A meta-analysis was performed using a random-effects model and grouped by the type of intervention. Conclusions: Twenty-nine studies were included, encompassing 2255 participants (mean age, 78.1 years; SD, 2.22). Amino acids, creatine, β-hydroxy-β-methylbutyrate, and protein with amino acids supplementation significantly improved muscle mass. No effect was found for protein supplementation alone, protein and other components, and polyunsaturated fatty acids. High interstudy variability was observed regarding the dose, duration, and frequency, coupled with inconsistency in reporting timing and adherence. Overall, several nutritional interventions could be effective to improve muscle mass measures in older adults. Because of the substantial variability of the intervention factors among studies, the optimum profile is yet to be established.
... Quiescent satellite cells are adhered to the myofiber with M-cadherin (Irintchev et al., 1994), and proliferation and differentiation are controlled by several growth factor families (Dusterhoft and Pette, 1999;Sheehan and Allen, 1999) or nitric oxide (Anderson, 2000). It is also reported that satellite cells are activated, when the muscle is over-loaded (Dangott et al., 2000) or injured (Schultz et al., 1985). ...
Article
It is well-reported that the morphological properties of skeletal muscles or muscle fibers, which are influenced by the level of protein synthesis and/or degradation, are regulated in response to mechanical load. However, the precise mechanism responsible for such phenomena is not fully understood yet. Changes of the distribution of satellite cells and/or myonuclei have been also noted in atrophied or hypertrophied skeletal muscle fibers, suggesting that the number and/or function of these parameters play essential roles in the regulation of morphological properties of muscle and muscle fibers. Thus, the roles of satellite cells and/or myonuclei in the regulation of morphological properties of anti-gravitational muscle, soleus and adductor longus, in response to the level of mechanical stress, with or without association of macrophage-related factors, were briefly reviewed. It was suggested that a regulatory network among macrophage, interleukin-6, heat shock transcription factor 1, and activation of transcription factor 3 may play a crucial role for the modulation of skeletal muscle mass and function, which are also influenced by activation of satellite cells and distribution of myonuclei.
... Satellite cells are most active the first week posthatch (Halevy et al., 2000;Mozdziak et al., 2002). They are sensitive to nutritional and environmental changes and will have long-term effects on muscle growth and meat quality (Dangott et al., 2000;Halevy et al., 2001;Velleman et al., 2014). Sufficient nutrients during the first week posthatch are critical for maximal muscle growth (Halevy et al., 2001;Powell et al., 2014), whereas nutrient restriction during the first week posthatch influences myogenic genes expression and fat deposition in broilers (Velleman et al., 2010Powell et al., 2014). ...
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The wooden breast (WB) myopathy is identified by the palpation of a rigid pectoralis major (P. major) muscle and is characterized as a fibrotic, necrotic P. major muscle disorder in broilers resulting in reduced breast meat quality. Breast muscle affected with WB is under severe oxidative stress and inflammation. The objectives were to identify the effects of dietary vitamin E (VE) and omega-3 (n-3) fatty acids independently or in combination when fed during the starter phase (0–10 D) or grower phase (11–24 D) on growth performance, meat yield, meat quality, and severity of WB myopathy and to determine the most beneficial dietary supplementation period. A total of 210 Ross 708 broiler chicks were randomly assigned into 7 experimental groups with 10 replicates of 3 birds each. The control group was fed with corn–soybean meal basal diet with VE (10 IU/kg) and n-3 fatty acids (n-6/n-3 ratio of 30:1) at a standard level during the entire study (0–58 D). Supplementation of VE (200 IU/kg), n-3 fatty acids (n-6/n-3 ratio of 3:1), or combination of both was performed during the starter phase or grower phase. Growth performance, meat yield, meat quality, and WB scores were obtained. There was no significant difference in final body weight and meat yield when VE was increased (P > 0.05). In contrast, n-3 fatty acids supplementation in starter diets significantly decreased final body weight, hot carcass weight, and chilled carcass weight of broilers (P ≤ 0.05). The P. major muscle from broilers supplemented with VE in starter diets had lower shear force than in grower diets (P ≤ 0.05). Supplemental VE reduced the severity of WB and in starter diets showed a more beneficial effect than those fed VE in the grower diets. These data are suggestive that additional supplementation of dietary VE may reduce the severity of WB and promote breast meat quality without adversely affecting growth performance and meat yield.
... It has been postulated that the associated increased cellular hydration may contribute to greater muscle hypertrophy by stimulating pathways that increase protein synthesis and suppressing those involved in protein degradation (Millar et al., 1997;Schoenfeld, 2012Schoenfeld, , 2013. It also has been theorized that the stimulus associated with cell hydration status may trigger proliferation of satellite cells and facilitate their fusion to hypertrophying myofibers (Dangott et al., 2000). Furthermore, Cr supplementation may promote increases in training volume (Branch, 2003;Kreider et al., 2010;Naderi et al., 2016;Rossouw et al., 2000;Volek et al., 1997), an outcome that may ultimately enhance neuromuscular adaptations. ...
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Background: Creatine supplementation associated with resistance training produces greater muscular strength improvements in the upper compared to lower body, however no study has investigated if such regional-specific results are seen with gains in muscle mass. Aim: To evaluate the effect of creatine (Cr) supplementation in combination with resistance training on lean soft tissue changes in the upper and lower limbs and trunk in resistance-trained young adult men. Methods: In a randomized, double-blind and placebo-controlled design, 43 resistance-trained men (22.7 ± 3.0 years, 72.9 ± 8.7 kg, 177.9 ± 5.7 cm, 23.0 ± 2.5 kg/m2) received either creatine (Cr, n = 22) or placebo (PLA, n = 21) over an eight-weeks study period. The supplementation protocol included a loading phase (7-days, 4 doses of 0.3g/kg per day) and a maintenance phase (7-weeks, single dose of 0.03g/kg per day). During the same period, subjects performed resistance training four times per week using the following two-way split routine; Monday and Thursday = pectoral, shoulders, triceps and abdomen, Tuesday and Friday = back, biceps, thighs and calves. Lean soft tissue of the upper limbs (ULLST), lower limbs (LLLST), and trunk (TLST) were assessed by dual-energy X-ray absorptiometry before and after the intervention. Results: Both groups showed significant (P < 0.001) improvements in ULLST, LLLST, TLST, and the Cr group achieved greater (P < 0.001) increases in these outcomes compared to PLA. For the Cr group, improvements in ULLST (7.1 ± 2.9%) were higher than those observed in LLLST (3.2 ± 2.1%) and TLST (2.1 ± 2.2%). Otherwise, for PLA group there was no significant difference in the magnitude of segmental muscle hypertrophy (ULLST = 1.6 ± 3.0%; LLLST = 0.7 ± 2.8%; TLST = 0.7 ± 2.8%). Conclusion: Our results suggest that Cr supplementation can positively augment muscle hypertrophy in resistance-trained young adult men, particularly in the upper limbs.
... This cellular swelling supports the increased protein synthesis in many different cell types including muscle fibers [28,60]. Cell swelling can indicate muscle growth through the proliferation and fusion of satellite cells [61]. ...
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Abstract: Background: The vascular effects of training under blood flow restriction (BFR) in healthy persons can serve as a model for the exercise mechanism in lower extremity arterial disease (LEAD) patients. Both mechanisms are, inter alia, characterized by lower blood flow in the lower limbs. We aimed to describe and compare the underlying mechanism of exercise‐induced effects of disease and external application‐BFR methods. Methods: We completed a narrative focus review after systematic literature research. We included only studies on healthy participants or those with LEAD. Both male and female adults were considered eligible. The target intervention was exercise with a reduced blood flow due to disease or external application. Results: We identified 416 publications. After the application of inclusion and exclusion criteria, 39 manuscripts were included in the vascular adaption part. Major mechanisms involving exercise‐mediated benefits in treating LEAD included: inflammatory processes suppression, proinflammatory immune cells, improvement of endothelial function, remodeling of skeletal muscle, and additional vascularization (arteriogenesis). Mechanisms resulting from external BFR application included: increased release of anabolic growth factors, stimulated muscle protein synthesis, higher concentrations of heat shock proteins and nitric oxide synthase, lower levels in myostatin, and stimulation of S6K1. Conclusions: A main difference between the two comparators is the venous blood return, which is restricted in BFR but not in LEAD. Major similarities include the overall ischemic situation, the changes in microRNA (miRNA) expression, and the increased production of NOS with their associated arteriogenesis after training with BFR.
... In-vitro and in-vivo evidence supports a positive effect of creatine on satellite cell differentiation and activity. Incubation of satellite cells in creatine monohydrate increased differentiation [36], while creatine supplementation in a group of rats exposed to compensatory hypertrophy of the plantaris muscle (induced by removal of the soleus and gastrocnemius) resulted in a greater increase in satellite cell number, than compensatory hypertrophy alone [37]. Human models have also demonstrated the potential of creatine supplementation to positively impact satellite cells, with supplementation of creatine monohydrate in conjunction with resistance training reported to augment satellite cell number to a greater extent than training alone [38]. ...
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Sarcopenia is characterized by a loss of muscle mass, quality, and function, and negatively impacts health, functionality, and quality of life for numerous populations, particularly older adults. Creatine is an endogenously produced metabolite, which has the theoretical potential to counteract many of the morphological and metabolic parameters underpinning sarcopenia. This can occur through a range of direct and indirect mechanisms, including temporal and spatial functions that accelerate ATP regeneration during times of high energy demand, direct anabolic and anti-catabolic functions, and enhanced muscle regenerating capacity through positively impacting muscle stem cell availability. Studies conducted in older adults show little benefit of creatine supplementation alone on muscle function or mass. In contrast, creatine supplementation as an adjunct to exercise training seems to augment the muscle adaptive response to the training stimulus, potentially through increasing capacity for higher intensity exercise, and/or by enhancing post-exercise recovery and adaptation. As such, creatine may be an effective dietary strategy to combat age-related muscle atrophy and sarcopenia when used to complement the benefits of exercise training.
... Since Cr supplementation has been shown to positively affect skeletal muscle in a variety of ways including acting as a spatial energy buffer (26), increasing PCr levels (27), enhancing muscle fiber size and increasing lean body mass (28), enhancing satellite cell activity (29), scavenging charged radicals (i.e., 2,2 0azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, superoxide anion, and peroxynitrite) (30), and protecting mitochondrial DNA from oxidative damage (31), it is possible that Cr supplementation may play a role in combatting Dox-induced skeletal muscle dysfunction. Recently, Cr was shown to protect against Dox-induced skeletal muscle dysfunction in an ex vivo, isolated skeletal muscle preparation (i.e., outside of the living organism) (32), but the effects of Cr supplementation on Dox myotoxicity in vivo (i.e., inside the living organism) has yet to be investigated. ...
Article
The purpose of this study was to investigate the effects of in vivo creatine monohydrate (Cr) supplementation on doxorubicin (Dox)-induced muscle dysfunction. Male rats were fed a diet supplemented with 3% Cr or a standard chow for 2 wk. After 2 wk of feeding, animals received Dox or saline as a placebo. Five days post-injection, grip strength was measured, and muscle fatigue was analyzed ex vivo. When compared with controls, a significantly lower grip strength was observed with Dox treatment, but no significant handgrip difference was observed with Cr feeding prior to Dox treatment when compared to controls. In the isolated muscle fatigue experiments, solei (primarily type I muscle) from controls produced significantly less force than baseline at 60 s and solei from Dox treated rats produced significantly less force than baseline at 30 s; however, Cr feeding prior to Dox produced significantly less force than baseline at 60 s. In the primarily type II EDL, a decline in force production from baseline was observed at 50 s in controls and Cr + Dox and at 20 s in standard chow + Dox. Cr attenuated the increase in fatigue that accompanies Dox treatment suggesting that Cr supplementation may have use in managing Dox myotoxicity.
... This suggests that CM supplementation did not promote gains in muscle mass beyond the effects observed with soccer training alone. This may be explained by the fact that (i) creatine does not have a direct anabolic effect on protein synthesis (39,40) and muscle hypertrophy (41), (ii) the benefits of the supplement seem mainly dependent on an increased training workload (42) and (iii) our groups were well matched for training load, and players spent limited time in the gym during the supplementation period (~50 min of strength and conditioning per week). Beyond asking participants to maintain the same diet throughout the supplementation period, we were unfortunately not in a position to control their food intake; this could have influenced muscle creatine content (43) and responses to the creatine supplement (5). ...
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Introduction: Owing to its well-established ergogenic potential, creatine is a highly popular food supplement in sports. As an oral supplement, creatine is considered safe and ethical. However, no data exist on the safety of creatine on lung function in athletes. The aim of this project was to evaluate the effects of a standard course of creatine on the airways of youth elite athletes. Methods: Nineteen elite soccer players, 16-21 yr old, completed a stratified, randomized, double-blind, placebo-controlled, parallel-group trial. The creatine group (n = 9) ingested 0.3 g·kg⋅d of creatine monohydrate (CM) for 1 wk (loading phase) and 5 g·d for 7 wk (maintenance phase), and the placebo group (n = 10) received the same dosages of maltodextrin. Airway inflammation (assessed by exhaled nitric oxide, FENO) and airway responsiveness (to dry air hyperpnoea) were measured pre- and postsupplementation. Results: Mild, unfavorable changes in FENO were noticed by trend over the supplementation period in the CM group only (P = 0.056 for interaction, η = 0.199), with a mean group change of 9 ± 13 ppb in the CM group versus -5 ± 16 ppb in the placebo group (P = 0.056, d = 0.695). Further, the maximum fall in forced expiratory volume in 1 s after dry air hyperpnoea was larger by trend postsupplementation in the CM group compared with the placebo group: 9.7% ± 7.5% vs 4.4% ± 1.4%, respectively (P = 0.070, d = 0.975). These adverse effects were more pronounced when atopic players only (n = 15) were considered. Conclusion: On the basis of the observed trends and medium to large effect sizes, we cannot exclude that creatine supplementation has an adverse effect on the airways of elite athletes, particularly in those with allergic sensitization. Further safety profiling of the ergogenic food supplement is warranted.
... Administration of nutrients, particularly whey protein, creatine, and L-carnitine would further enhance the process of muscle hypertrophy. Researches showed that whey protein and creatine could improve myoblast proliferation and differentiation [12,13]. Meanwhile, L-carnitine was involved in muscle recovery [14] and reduced muscle tissue damage [15]. ...
... Such results suggest that, in vivo, creatine's anabolic effects may be mediated by both direct (via the Akt-PKB pathway) or indirect (cell swelling related) mechanisms. In support of the direct myogenic theory, it has been demonstrated that creatine strongly influences satellite cell activation and posttranslational phosphorylation of proteins [108,110] and such effect may be responsible for the increased muscle hypertrohy observed in an animal model of compensatory hypertrophy [111]. Moreover, creatine supplementation increases the expression of mRNA coding for insulin-like growth factor [91] and increases mRNA expression of myogenic regulatory factor 4 in association with resistance training in human muscles [112]. ...
Article
Increased blood flow via vasodilation, metabolite production, and venous pooling contribute to the hyperaemia and cellular swelling experienced during resistance training. These effects have been suggested to play a role in hypertrophic adaptations. Over the past two decades sport supplement products have been marketed to promote exercise hyperaemia and intracellular fluid storage, and thereby enhance hypertrophy via acute swelling of myocytes. The three main classes of supplements hypothesized to promote exercise-induced hyperaemia include: vasodilators, such as nitric oxide precursor supplements; anaerobic energy system ergogenic aids that increase metabolite production, such as beta-alanine and creatine; and organic osmolytes, such as creatine and betaine. Previous studies indicated that these dietary supplements are able to improve muscle performance and thus enhance muscle hypertrophy; however, recent evidences also point to these three classes of supplements affecting “secondary” physiological determinants of muscle mass accretion such as vasodilation, metabolite accumulation and muscle cellular swelling. Although we recognize that the literature is relatively scarce regarding these topics, a better comprehension and discussion of these determinants can lead to increased knowledge and guide further research regarding the proposed mechanisms of action of the identified compounds. In this case, increased knowledge may contribute to the development of improved efficacy, new products, or direct new research to specifically investigate those secondary effects. From this discussion, new perspectives associated with “secondary physiological effects” induced by supplementation will be brought into focus and its relevance will be determined.
... Muscle cell swelling may stimulate genes (i.e., myosin heavy chain I and IIA) regulating various anabolic signaling pathways 18 . Furthermore, creatine increases satellite cell differentiation 19 , activity 20 , and content 21 ; myogenic transcription factor activity 22 , hormonal secretions (e.g. IGF-1; 23 ), muscle protein kinetics 24 , and decreases inflammation 25 . ...
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The combination of creatine monohydrate supplementation and resistance training increases muscle mass and strength. In this brief narrative review, we propose that the timing of creatine supplementation in relation to resistance training may be an important factor to optimize hypertrophy and strength gains. Meta-analyses indicated that creatine supplementation immediately after resistance training was superior for increasing muscle mass compared to creatine supplementation immediately before resistance training (3 studies, standard mean difference 0.52, 95% CI 0.03-1.00, p = 0.04); however, this did not translate into greater muscular strength (p > 0.05). Further research is needed to confirm these limited findings and to determine the mechanisms explaining the potential greater increase in muscle mass from post-exercise creatine.
... We included only studies combining creatine supplementation (with or without other nutritional supplements) with resistance training as creatine is minimally effective for enhancing cellular responses, leading to muscle hypertrophy if muscle loading is not present. 15 The comparator was resistance training without creatine supplementation. The outcomes we assessed were whole-body lean tissue mass, determined with dual-energy X-ray absorptiometry, hydrostatic weighing, or air displacement plethysmography, and chest press and leg press muscular strength, representing global measures of upper and lower body strength, respectively. ...
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The loss of muscle mass and strength with aging results in significant functional impairment. Creatine supplementation has been used in combination with resistance training as a strategy for increasing lean tissue mass and muscle strength in older adults, but results across studies are equivocal. We conducted a systematic review and meta-analysis of random-ized controlled trials of creatine supplementation during resistance training in older adults with lean tissue mass, chest press strength, and leg press strength as outcomes by searching PubMed and SPORTDiscus databases. Twenty-two studies were included in our meta-analysis with 721 participants (both men and women; with a mean age of 57-70 years across studies) randomized to creatine supplementation or placebo during resistance training 2-3 days/week for 7-52 weeks. Creatine supplementation resulted in greater increases in lean tissue mass (mean difference =1.37 kg [95% CI =0.97-1.76]; p<0.00001), chest press strength (standardized mean difference [SMD] =0.35 [0.16-0.53]; p=0.0002), and leg press strength (SMD =0.24 [0.05-0.43]; p=0.01). A number of mechanisms exist by which creatine may increase lean tissue mass and muscular strength. These are included in a narrative review in the discussion section of this article. In summary, creatine supplementation increases lean tissue mass and upper and lower body muscular strength during resistance training of older adults, but potential mechanisms by which creatine exerts these positive effects have yet to be evaluated extensively.
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Cellular swelling, often referred to as "the pump," has been shown to mediate increases in muscle protein synthesis and decreased protein degradation. This paper will explore the potential hypertrophic benefits associated with the pump and discuss practical implications for resistance training program design.
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Since 1992, creatine has been used successfully by athletes to improve their physical performance. Following this, and based on the observation that the intracellular concentration of creatine and the number of plasmacellular creatine transporters are reduced in various muscle diseases (mitochondrial myopathies, dystrophies, myositis), creatine has been administered to patients with a variety of muscle disorders in the last few years. The majority of the clinical studies performed in patients with various muscle disorders showed non-specific increases (about 15%) of isometric strength which were independent of the type of disorder. Two studies could not demonstrate any positive effects of creatine supplementation. Even the positive studies give rise to doubt about the practical relevance for everyday life of the parameters which showed an improvement. There were no significant side effects of creatine supplementation in any of the studies. - In view of the lack of specific therapeutic options in many myopathies we recommend to use creatine in such patients on a trial basis.
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Background The potential for prehabilitation programs to impact clinical outcomes is uncertain in abdominal cancer patients due to the short window of time to intervene and the weakened state of the patients. To improve the effectiveness of prehabilitation intervention, a multimodal sports science approach was implemented. Methods Prior to cancer-related surgery, 21 patients participated in a 4-week exercise and nutrition prehabilitation program comprised of blood flow restriction exercise (BFR) and a sports nutrition supplement. Retrospective data of 71 abdominal cancer patients who underwent usual preoperative care was used as a comparator control group (CON). At 90 days post-surgery, clinical outcomes were quantified. Results Prehabilitation was associated with a shorter length of hospital stay ( P = .02) with 5.5 fewer days (4.7 ± 2.1 vs 10.2 ± 1.2 days in CON) and decreased incidence of any complications ( P = .03). Prehabilitation was not related to incidence of serious complications ( P = .17) or readmission rate ( P = .59). The prehabilitation group recorded 58% more steps on day 5 after surgery ( P = .043). Discussion A 4-week home-based prehabilitation program composed of BFR training and sports nutrition supplementation was effective in reducing postoperative complications and length of hospital stay in older patients with abdominal cancer. ClinicalTrials.gov Identifier: NCT04073381.
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In recent years the research problem in the field of sports supplementation has changed to explain the metabolic mechanisms by which creatine (Cr) administration enhances the performance of certain sports or simply benefits the muscular adaptation. In this review for first time the biochemical mechanisms of Cr ingestion in a cell signaling insight were analyzed, focusing on energetic bioavailability enhancement and optimization of the temporal and spatial buffering of Cr/PCr/CK system. Moreover, intensification in proliferation and differentiation processes of muscle cells (IGF-I/PI3K/Akt-PKB, SPHK1/MAPK/p38/MRFs, mTOR, cellular swelling, mitotic activity of satellite cells, actin polymerization, and myoblast fusion) and inactivation and/or reduction in the expression of ergolitic metabolites (GSK3β, myostatin and AMPK regulation) were examined. In this way, we explained from a metabolic point of view the increase in muscle mass, strength, fatigue resistance, and performance of high intensity sports after Cr monohydrate supplementation.
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Foam fractionation is a cost-effective water treatment technology and it uses bubbles as the media for separating surfactants or non-surface materials from their aqueous solutions, where non-surface materials can be attached to the gas–liquid interface by using a surfactant as the collector. A novel two-stage batch foam fractionation was developed for recovering creatine from its wastewater. The objective of the first stage was to concentrate creatine from its wastewater and sodium dodecyl sulfate (SDS) was used as the collector. Under the suitable operating conditions, the enrichment ratio and the recovery percentage of creatine were 3.1 and 70.6%, respectively. Subsequently, the second stage was performed for isolating SDS from creatine by using the first stage foamate as the feeding solution. Under the suitable operating conditions, the recovery percentage of SDS reached 76.2% and creatine was massively remained in the residual solution because the complexation between creatine and SDS was eliminated through adjusting pH to 8.0. So, the total recovery percentage of creatine reached 59.3% and SDS in the second stage foamate could be reused for recovering creatine from its wastewater.
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Introduction: The use of pharmacologic and nutritional ergogenic supplements is growing every day in sports environment. Creatine and anabolic steroids are the most popular ergogenic resources used lately. Objective: To evaluate the histological and morphometric changes of the soleus muscle of rats receiving supplements and submitted to physical training (swimming). Methods: 50 rats were allocated into five groups: three did not undergo physical activity (controls) and two that received swimming training (trained). A control group received only rat chow (control chow group), two groups (one control and one trained) received 3.3mg of creatine per gram of diet dissolved in water daily applied orally via gavage, and the other two groups (control and other trained) received intramuscular injections of the anabolic steroid nandrolone decanoate (Deca-durabolin (R) - Organon) 5mg/kg twice weekly. The trained groups were submitted to the physical training 60min/day lasting from Monday to Friday for 9 weeks and were sacrificed at the end of the period. After sacrifice, the soleus muscle was removed, fixed in buffered formalin (10%) and embedded in paraffin. The histological sections were stained by hematoxylin-eosin for evaluation of muscle hyperplasia and hypertrophy. For data analysis we applied the One-Way ANOVA with post hoc Tukey-Kramer significance level of 5%. Results: It was shown that creatine during exercise probably increase the interstitial space in skeletal muscle without changing the size or number of muscle fibers, whereas the anabolic agent increased the number of muscle fibers per muscle area examined, though no changes have been observed in the area of the fiber. Conclusion: The muscle of rats submitted to swimming training responds differently opposite type of ergogenic aid used.
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New findings: What is the central question of this study? The purpose of this study was to determine if the nucleotides in a nucleoprotein diet could ameliorate the unloading-associated decrease in soleus muscle mass and fiber size. What is the main finding and its importance? The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fiber size and muscle mass most likely due to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus nucleotide supplementation appears to be an effective countermeasure for muscle atrophy. Abstract: Hindlimb unloading decreases both protein synthesis pathway and satellite cell activation results in muscle atrophy. Nucleotides are included in nucleoprotein and provide the benefits of increasing ERK1/2 phosphorylation. ERK 1/2 phosphorylation is also important in the activation of satellite cells, especially for myoblast proliferation and stimulating protein synthesis pathways. Therefore, we hypothesized that nucleotide in the nucleoproteins would ameliorate muscle atrophy via increasing the protein synthesis pathways and satellite cell activation during hindlimb unloading in rat soleus. Twenty-four female Wistar rats were divided into four groups: control rats fed a basal diet without nucleoprotein (CON), control rats fed a nucleoprotein-enriched diet (CON+NP), hindlimb unloaded rats fed a basal diet (HU), or hindlimb unloaded rats fed a NP diet (HU+NP). HU for two-weeks resulted in decreases in p70S6K- and rpS6-phosphorylation, the numbers of MyoD and myogenin, type I muscle fiber size, and muscle mass. Both CON and HU rats fed the NP diet showed an increase in ERK1/2, p70S6K- and rpS6-phosphorylation, and in the number of MyoD and myogenin compared to their basal diet groups. The NP diet also ameliorated the unloading-associated decrease in type I muscle fiber size and muscle mass. The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fiber size and muscle mass most likely due to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus nucleotide supplementation appears to be an effective countermeasure for muscle atrophy. This article is protected by copyright. All rights reserved.
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INTRODUÇÃO: O uso de suplementos ergogênicos farmacológicos e nutricionais cresce a cada dia no ambiente esportivo. A creatina e os esteroides anabólicos são os recursos ergogênicos mais procurados ultimamente. OBJETIVO: Avaliar as alterações histológicas e morfométricas do músculo sóleo de ratos que receberam suplementos e foram submetidos a treinamento físico (TF) de natação. MÉTODOS: Foram utilizados 50 ratos, distribuidos em cinco grupos: três não submetidos à atividade física (controles) e dois que receberam treinamento de natação (treinados). Um grupo controle recebeu apenas ração (grupo controle ração), dois grupos (um controle e outro treinado) receberam diariamente 3,3 mg de creatina por grama de dieta dissolvida em água aplicada oralmente via gavagem, e os outros dois grupos (um controle e outro treinado) receberam injeção intramuscular do esteroide anabolizante decanoato de nandrolona (Deca-durabolin(r) - Organon) 5 mg/kg duas vezes por semana. Os grupos treinados foram submetidos ao TF com duração de 60 min/sessão de segunda a sexta-feira por nove semanas, e foram sacrificados no final deste período. Após o sacrifício, o músculo sóleo foi retirado, fixado em formalina (10%) tamponada e incluído em parafina. Os cortes histológicos foram corados pela técnica de hematoxilina-eosina para avaliação de hiperplasia e hipertrofia muscular. Para análise dos dados aplicou-se a análise de variância ANOVA One-Way com post hoc de Tukey-Kramer com nível de significância de 5%. RESULTADOS: Foi demonstrado que a creatina associada ao exercício provavelmente aumente o espaço intersticial no músculo esquelético sem alterar o tamanho ou número de fibras musculares, enquanto que o anabolizante aumentou o número de fibras musculares por área de músculo analisada, embora nenhuma alteração tenha sido observada na área da fibra. CONCLUSÃO: O músculo de ratos submetidos ao treinamento de natação responde diferentemente frente ao tipo de recurso ergogênico utilizado.
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Protein synthesis in rat plantaris muscle undergoing surgically induced hypertrophy was studied using a perfused hindquarter preparation. The tissue mass of the hypertrophied muscle increased 11, 33, 33, and 104% at 2, 5, 15, and 50 days postsurgery. Total tissue protein synthesis was unchanged during the early phase but was significantly elevated after 15 and 50 days of work overload. Myosin synthesis was also significantly elevated after 15 and 50 days of hypertrophic growth. Increases in muscle protein content (milligrams per muscle) for each protein fraction examined were temporally in step with the altered synthetic rates. The shift in muscle fibre-type profile from approximately 10% alkaline-labile fibres in the control muscle to about 25% alkaline-labile fibres in the hypertrophied muscle also followed a similar time course. These data suggest that during compensatory hypertrophy, enhanced protein synthesis may be the dominant mechanism for the massive accumulation of muscle protein. However, its contribution to muscle growth does not become evident until about 15 days after the initial growth stimulus.
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Nine male subjects performed two bouts of 30-s maximal isokinetic cycling before and after ingestion of 20 g creatine (Cr) monohydrate/day for 5 days. Cr ingestion produced a 23.1 +/- 4.7 mmol/kg dry matter increase in the muscle total creatine (TCr) concentration. Total work production during bouts 1 and 2 increased by approximately 4%, and the cumulative increases in both peak and total work production over the two exercise bouts were positively correlated with the increase in muscle TCr. Cumulative loss of ATP was 30.7 +/- 12.2% less after Cr ingestion, despite the increase in work production. Resting phosphocreatine (PCr) increased in type I and II fibers. Changes in PCr before exercise bouts 1 and 2 in type II fibers were positively correlated with changes in PCr degradation during exercise in this fiber type and changes in total work production. The results suggest that improvements in performance were mediated via improved ATP resynthesis as a consequence of increased PCr availability in type II fibers.
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The study was designed to investigate the effect of creatine monohydrate ingestion (20 g daily for 5 days) on performance in 45 s maximal continuous jumping and in all-out treadmill running at 20 km x h(-1), (inclination 5 degrees, duration approximately 60s). The participants were qualified sprinters and jumpers. The effect of creatine was compared with placebo in a double-blind design. Creatine (Cr) supplementation led to a significant enhancement of performance capacity in the jumping test by 7% during the first 15 s and by 12% during the second 15 s of the exercise. The positive effect of Cr supplementation was not observed in the last third of the continuous jumping exercise, when the contribution of anaerobic metabolism was decreasing. The time of intensive running up to exhaustion improved by 13%. The results show that Cr supplementation helps to prolong the time during which the maximal rate of power output could be maintained.
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The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 +/- 8 vs. 123 +/- 16 mg. Muscle weight in the FO + GH/IGF-I group (196 +/- 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 +/- 445 microm2) was increased compared with the Con (2,044 +/- 108 microm2) and FO (2,267 +/- 301 microm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 +/- 15 myonuclei/mm) and FO + GH/IGF-I (217 +/- 23 myonuclei/mm) rats compared with Con (155 +/- 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.
Article
Hypertrophy of the plantaris muscle was induced in male and female rats by myectomy of the synergistic gastrocnemius muscle. Selected histochemical and biochemical characteristics were studied to establish the time required to achieve a steady-state hypertrophy and to determine the metabolic character of chronically enlarged muscle. The plantaris muscle hypertrophied 38% by 2 days postmyectomy. Compensatory growth was completed by 30 days and, thereafter, maintained a relative enlargement of approximately 80%. Protein concentration (-17%), succinate dehydrogenase (DH) (-34%), and phosphofructokinase (-38%) activities were less for the first 2-5 days but returned to normal by 30 days. The percentage of slow-twitch fibers increased two to threefold by 30 days. During the relative steady-state hypertrophy, hexokinase, glutamate-pyruvate transaminase, malate DH, and aspartate transaminase activities were unchanged. Glycerol phosphate DH and 3-hydroxyacyl-CoA DH activities were increased; whereas, lactate DH was lower than normal. It was concluded that a sustained, relative steady-state hypertrophy for this model is established within 30 days and that the metabolic character of hypertrophied muscle undergoes only minor changes.
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1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated. 2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak. 3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%. 4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content. 5. No side effects of creatine supplementation were noted. 6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
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The effects of long-term hindlimb unweighting by tail suspension on postnatal growth of 20-day rat extensor digitorum longus (EDL) and soleus muscles were studied. Morphological assay indicated that radial growth of soleus myofibers was completely inhibited between 3 and 10 days of suspension and reduced thereafter, leading to a severe attenuation (-76% from control) over the total experimental period. Longitudinal growth rate, however, was accelerated 40% over weight-bearing controls. In addition, myofibers were arranged parallel to the long axis of the muscle, an orientation associated with chronologically younger muscles, suggesting morphological maturation of the soleus muscle had been delayed by suspension. In contrast, radial and longitudinal growth of EDL myofibers were minimally affected under similar conditions and remained within approximately 5% of control at all times. Suspension also influenced the normal changes that occur in satellite cell and myonuclear populations during postnatal growth. Both the number and proliferative activity of satellite cells were severely reduced in individual myofibers after only 3 days in both soleus and EDL muscles. The reduced number of satellite cells within 3 days of initiating hindlimb suspension appeared to be the result of their incorporation into myofibers while the long-lasting reduction appeared to be the added effects of decreased proliferative activity. In the soleus, this reduction in number and proliferation of satellite cells persisted throughout the experimental period and resulted in an overall 43% fewer myonuclei and 45% fewer satellite cells than control at 50 days of age. In contrast, both the total number and mitotic activity of satellite cells in the EDL rapidly returned to weight-bearing control levels by day 10 of suspension, resulting in no overall reduction in myonuclear accretion.
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The time course and pattern of the initiation of satellite cell mitoses was studied following a crush injury of the distal third of the 30-day-old rat extensor digitorum longus, a muscle in which myofibers run the entire length of the belly. Satellite cell mitotic activity was monitored using autoradiography after injection of 3H-thymidine. Satellite cell labeling rose above control values by 15 hours post injury at the injured site and by 20 hours in the middle third or adjacent undamaged portion of the muscle. Labeling decreased in the proximal third of the muscle, so that by 25 hours post injury, a gradient of labeling was established along the muscle length. Electron microscopy (EM) quantitation showed that the reduced labeling in the proximal third resulted from a reduction in satellite cell numbers. The results suggest that mitotic activity of satellite cells after localized injury occurs mainly at or near the site of injury, but that many of the dividing cells have migrated from undamaged areas distant from the lesion site.
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The source of the new nuclei appearing during the growth of muscle fibers was examined in the tibialis anterior muscle of young Sherman rats (14–17 days of age) using radioautography at various intervals after a single injection of a small, non-toxic dose of 3H-thymidine (2 μCi/g body weight). Two techniques were employed: (1) labeled nuclei were detected in 1 μ thick radioautographs examined in the light microscope, and identified by simultaneous electron microscope examination of an adjacent section. The nuclei were then classified either as “true” muscle nuclei (within the plasmalemma of the fibers) or as belonging to “satellite cells” (which are mononucleated cells with scanty cytoplasm wedged between plasmalemma and basement membrane). (2) Muscle fibers freed by collagenase digestion were radioautographed one hour after 3H-thymidine injection in order to determine the total number of labeled nuclei (true muscle nuclei plus those of satellite cells) per unit length of fiber.Certain nuclei within the basement membrane of muscle fibers are labeled one hour after 3H-thymidine and, therefore, synthesize DNA. The electron microscope demonstrates that these nuclei invariably belong to satellite cells, never to true muscle nuclei. Furthermore, the total number of labeled nuclei per unit length of fiber doubles between 1 and 24 hours; and, therefore, the labeled satellite cell nuclei undergo mitosis.Following mitosis, half of the daughters of satellite cells are incorporated into the fibers to become true muscle nuclei. The remaining half divides again later; and half of their daughter cells are incorporated. Thus, satellite cells in young rats divide repeatedly and function as a source of true muscle nuclei.
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Gyrate atrophy of the choroid and retina is a disease characterized by progressive constriction of visual fields, a 10-fold to 20-fold elevation in plasma ornithine, and depressed activity of L-ornithine:2 oxoacid aminotransferase. Morphologically conspicuous but clinically unimportant atrophy of Type II muscle fibers progresses concomitantly with the eye disease. A pathogenic component of the disease may be deficient formation of creatine, caused by hyperornithinemia, which leads to a shortage of cellular phosphocreatine energy stores. To test the therapeutic value of replenishing the postulated deficiency of creatine, we supplemented the diet of seven patients with 1.5 g of creatine daily. During one year of this treatment the diameters of Type II muscle fibers increased from 34.1 +/- 7.1 to 49.9 +/- 7.0 micron (mean +/- S.D.) (P less than 0.001). There was no significant increase in the diameters of Type I fibers. The visual-field tests showed no further constriction during the therapy. Fundus photography revealed slow impairment at an age otherwise associated with rapid progression of the disease. These promising preliminary results need further evaluation with long-term follow-up studies.
Article
Biopsy samples were obtained from the vastus lateralis muscle of eight subjects after 0, 20, 60, and 120 s of recovery from intense electrically evoked isometric contraction. Later (10 days), the same procedures were performed using the other leg, but subjects ingested 20 g creatine (Cr)/day for the preceding 5 days. Muscle ATP, phosphocreatine (PCr), free Cr, and lactate concentrations were measured, and total Cr was calculated as the sum of PCr and free Cr concentrations. In five of the eight subjects, Cr ingestion substantially increased muscle total Cr concentration (mean 29 +/- 3 mmol/kg dry matter, 25 +/- 3%; range 19-35 mmol/kg dry matter, 15-32%) and PCr resynthesis during recovery (mean 19 +/- 4 mmol/kg dry matter, 35 +/- 6%; range 11-28 mmol/kg dry matter, 23-53%). In the remaining three subjects, Cr ingestion had little effect on muscle total Cr concentration, producing increases of 8-9 mmol/kg dry matter (5-7%), and did not increase PCr resynthesis. The data suggest that a dietary-induced increase in muscle total Cr concentration can increase PCr resynthesis during the 2nd min of recovery from intense contraction.
Article
The right extensor digitorum longus (EDL) muscle of growing male rats was overloaded by ablation of its synergist tibialis anterior (TA) muscle. Four weeks later, the overloaded muscle was heavier and contained larger type IIA, IIX and IIB fibres than either untreated contralateral muscle or control muscle from an untreated animal. The myonuclear-to-myoplasmic volume ratio was maintained in the overloaded muscle. Overloaded EDL muscle, previously subjected to a dose of irradiation sufficient to sterilise satellite cells, and EDL muscle which had been only irradiated, were significantly lighter and contained significantly smaller fibres than controls, though a significant amount of normal EDL muscle growth did occur following either treatment. The myonuclear-to-myoplasmic volume ratio of the irradiated muscles was smaller than in controls. Overloaded muscle, with or without prior irradiation, possessed a smaller proportion of fibres containing IIB myosin heavy chain (MHC) and a larger proportion of fibres containing IIA and IIX MHC; a significant percentage of these fibres coexpressed either type IIA and IIX MHC or type IIX and IIB MHC. Thus in the absence of satellite cell mitosis, muscles of young rats possess a limited capacity for normal growth but not for compensatory hypertrophy. Adaptations in MHC gene expression to chronic overload are completely independent of satellite cell activity.
Article
This study investigated the effect of carbohydrate (CHO) ingestion on skeletal muscle creatine (Cr) accumulation during Cr supplementation in humans. Muscle biopsy, urine, and plasma samples were obtained from 24 males before and after ingesting 5 g Cr in solution (group A) or 5 g Cr followed, 30 min later, by 93 g simple CHO in solution (group B) four times each day for 5 days. Supplementation resulted in an increase in muscle phosphocreatine (PCr), Cr, and total creatine (TCr; sum of PCr and Cr) concentration in groups A and B, but the increase in TCr in group B was 60% greater than in group A (P < 0.01). There was also a corresponding decrease in urinary Cr excretion in group B (P < 0.001). Creatine supplementation had no effect on serum insulin concentration, but Cr and CHO ingestion dramatically elevated insulin concentration (P < 0.001). These findings demonstrate that CHO ingestion substantially augments muscle Cr accumulation during Cr feeding in humans, which appears to be insulin mediated.
Article
Several reports have shown that the use of oral creatine (Cr) supplementation can increase performance during brief high intensity exercise in humans. The purpose of this study was to examine the separate and combined effects of Cr supplementation and high intensity run training on the performance capacity and biochemical properties of rodent skeletal muscle. Running performance was assessed following acute (10-d) and chronic (4-wk) Cr supplementation. Results indicate that Cr supplementation alone has ergogenic effects and the combination of run training plus Cr results in a more pronounced enhancement of performance than either intervention alone. The benefits of Cr supplementation were seen most clearly during repetitive bouts of high intensity interval running. Cr concentrations increased in both the slow soleus and fast plantaris muscles (P < 0.05) in response to Cr supplementation. Increased creatine concentrations appeared to be reflected in increased phosphorylated creatine (PCr). Citrate synthase (CS) activity was increased in both the soleus and plantaris muscles following training (P < 0.05). CS activity of the untrained soleus but not the plantaris responded to the dietary stimulus. There were no significant changes in either creatine phosphokinase activity or myosin heavy chain isoform distribution following training or supplementation. These results indicate that the gains in high intensity running performance seen following Cr loading are a combined result of increased aerobic (CS) and anaerobic (Cr and PCr) energy buffering capacity of the muscle.
Article
The role of satellite cells and DNA unit size in determining skeletal muscle growth was studied after mitotic activity was inhibited in the left pectoralis thoracicus of 2-wk-old tom turkeys by means of a 25-Gy dose of irradiation. Toms were killed and muscle weights were obtained 1 (n = 5), 4 (n = 6), 7 (n = 6), and 15 (n = 4) wk after irradiation. Satellite cell mitotic activity and DNA unit size were determined using enzymatically isolated myofiber segments and image analysis. Irradiated and nonirradiated muscle weights increased (P < 0.01) between all ages examined, but irradiated muscle weights were significantly (P < 0.01) lower than nonirradiated muscle weights at 4, 7, and 15 wk after irradiation. Satellite cell mitotic activity was lower (P < 0.01) in irradiated than in nonirradiated muscles at 1 and 4 wk after irradiation and resulted in a significant reduction (P < 0.05) in the number of myofiber nuclei per millimeter at 4 and 7 wk after irradiation. Satellite cell mitotic activity was higher (P < 0.05) in irradiated than in nonirradiated muscles at 7 wk after irradiation, but at 15 wk after irradiation it had fallen to low levels in both muscles. There was no significant (P > 0.10) difference in DNA unit size between muscles at any time, but there was an age-related increase (P < 0.01) for both muscles. Irradiation reduced muscle growth through a transient reduction in myonuclear production at a critical time (3-6 wk of age) in posthatch skeletal muscle development. The age-related increase in DNA unit size was not accelerated to compensate for the reduction in myonuclear accretion. Thus it appears that muscle growth potential is governed mostly by myonuclear accretion and to a lesser extent by DNA unit size.
Article
The effects of 1 and 10 wk of functional overload (FO) of the rat plantaris with (FOTr) and without daily endurance treadmill training on its myosin heavy chain (MHC) composition were studied. After 1 and 10 wk of FO, plantaris mass was 22 and 56% greater in FO and 37 and 94% greater, respectively, in FOTr rats compared with age-matched controls. At 1 wk, pure type I and pure type IIa MHC fibers were hypertrophied in FO (39 and 44%) and FOTr (70 and 87%) rats. By 10 wk all fiber types comprising >5% of the fibers sampled showed a hypertrophic response in both FO groups. One week of FO increased the percentage of hybrid (containing both type I and type IIa MHC) fibers and of fibers containing embryonic MHC. By 10 wk, the percentage of pure type I MHC fibers was approximately 40% in both FO groups compared with 15% in controls, and the percentage of fibers containing embryonic MHC was similar to that in controls. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses showed an increase in type I MHC and a decrease in type IIb MHC in both FO groups at 10 wk, whereas little change was observed at 1 wk. These data are consistent with hypertrophy and transformation from faster to slower MHC isoforms in chronically overloaded muscles. The additional overload imposed by daily endurance treadmill training employed in this study (1.6 km/day; 10% incline) results in a larger hypertrophic response but appears to have a minimal effect on the MHC adaptations.
Article
Creatine supplementation has become a common practice among competition athletes participating in different sports over the last few years. The mechanism by which supplementary creatine could have potential ergogenic effects would be an increased muscle creatine and phosphocreatine concentration, leading to a higher rate of ATP resynthesis, a delay in the onset of muscular fatigue and a facilitated recovery during repeated bouts of high-intensity exercise. A critical review of the literature reveals that these ergogenic effects, when found, have been generally shown in untrained subjects performing several exercise bouts under laboratory conditions. The limited body of scientific data available concerning highly trained athletes performing single competition-like exercise tasks indicates that this type of population does not benefit from creatine supplementation. Therefore, the widespread use of creatine ingestion to improve competition performance does not seem to be justified. The potential interest of creatine supplementation for elite athletes could be related to an increased ability to perform repeated high-intensity exercise bouts, either during training or during competition in sports in which repeated efforts are required (e.g. soccer, basketball), but this possibility needs scientific confirmation.
Exposure of juvenile skeletal muscle to a weightless environment reduces growth and satellite cell mitotic activity. However, the effect of a weightless environment on the satellite cell population during muscle repair remains unknown. Muscle injury was induced in rat soleus muscles using the myotoxic snake venom, notexin. Rats were placed into hindlimb-suspended or weightbearing groups for 10 days following injury. Cellular proliferation during regeneration was evaluated using 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and image analysis. Hindlimb suspension reduced (P < 0.05) regenerated muscle mass, regenerated myofiber diameter, uninjured muscle mass, and uninjured myofiber diameter compared to weightbearing rats. Hindlimb suspension reduced (P < 0.05) BrdU labeling in uninjured soleus muscles compared to weight-bearing muscles. However, hindlimb suspension did not abolish muscle regeneration because myofibers formed in the injured soleus muscles of hindlimb-suspended rats, and BrdU labeling was equivalent (P > 0.10) on myofiber segments isolated from the soleus muscles of hindlimb-suspended and weightbearing rats following injury. Thus, hindlimb suspension (weightlessness) does not suppress satellite cell mitotic activity in regenerating muscles before myofiber formation, but reduces growth of the newly formed myofibers.
Article
Differentiating muscle cells synthesizing myosin, the meromyosins, and actin do not concurrently synthesize DNA. Presumptive myoblasts which synthesize DNA do not concurrently synthesize myosin, the meromyosins or actin. The multinucleated skeletal muscle fiber is the product of cell fusion.
SAS User's Guide: Statistics. Cary NC: SAS Institute
  • Sas Institute
SAS Institute. SAS User's Guide: Statistics. Cary NC: SAS Institute, 1985
Quantification of satellite cells in growing muscle using electron microscopy and fiber whole mounts
  • E Schultz
Schultz E. Quantification of satellite cells in growing muscle using electron microscopy and fiber whole mounts. In: Mauro A (ed). Muscle Regeneration. New York: Raven, 1979: 131 -135