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European journal of applied physiology 2010 Feb; 108(4)
Increased p70s6k phosphorylation during intake of a protein-carbohydrate drink following resistance exercise in the fasted state.
The present study aimed at comparing the responses of myogenic regulatory factors and signaling pathways involved in muscle protein synthesis after a resistance training session performed in either the fasted or fed state. According to a randomized c... expand abstractrossover study design, six young male subjects participated in two experimental sessions separated by 3 weeks. In each session, they performed a standardized resistance training. After the sessions, they received during a 4-h recovery period 6 ml/kg b.w. h of a solution containing carbohydrates (50 g/l), protein hydrolysate (33 g/l), and leucine (16.6 g/l). On one occasion, the resistance exercise session was performed after the intake of a carbohydrate-rich breakfast (B), whereas in the other session they remained fasted (F). Needle biopsies from m. vastus lateralis were obtained before (Rest), and 1 h (+1h) and 4 h (+4h) after exercise. Myogenin, MRF4, and MyoD1 mRNA contents were determined by RT-PCR. Phosphorylation of PKB (protein kinase B), GSK3, p70(s6k) (p70 ribosomal S6 kinase), eIF2B, eEF2 (eukaryotic elongation factor 2), ERK1/2, and p38 was measured via western blotting. Compared with F, the pre-exercise phosphorylation states of PKB and p70(s6k) were higher in B, whereas those of eIF2B and eEF2 were lower. During recovery, the phosphorylation state of p70(s6k) was lower in B than in F (p = 0.02). There were no differences in basal mRNA contents between B and F. However, compared with F at +1h, MyoD1 and MRF4 mRNA contents were lower in B (p < 0.05). Our results indicate that prior fasting may stimulate the intramyocellular anabolic response to ingestion of a carbohydrate/protein/leucine mixture following a heavy resistance training session. collapse abstract
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The Journal of nutrition 2010 Feb; 140(3)
Changes in intestinal bifidobacteria levels are associated with the inflammatory response in magnesium-deficient mice.
Magnesium (Mg) deficiency is a common nutritional disorder that is linked to an inflammatory state characterized by increased plasma acute phase protein and proinflammatory cytokine concentrations. Recent studies have shown that changes in the compos... expand abstractition of gut microbiota composition participate in systemic inflammation. In this study, therefore, we assessed the potential role of gut microbiota in intestinal and systemic inflammation associated with Mg deficiency in mice. For this purpose, mice were fed a control or Mg-deficient diet (500 mg vs. 70 mg Mg/kg) for 4 or 21 d. Compared with the mice fed the control diet, mice fed the Mg-deficient diet for 4 d had a lower gut bifidobacteria content (-1.5 log), a 36-50% lower mRNA content of factors controlling gut barrier function in the ileum (zonula occludens-1, occludin, proglucagon), and a higher mRNA content (by approximately 2-fold) in the liver and/or intestine of tumor necrosis factor-alpha, interleukin-6, CCAAT/enhancer binding protein homologous protein, and activating transcription factor 4, reflecting inflammatory and cellular stress. In contrast, mice fed the Mg-deficient diet for 21 d had a higher cecal bifidobacteria content compared with the control group, a phenomenon accompanied by restoration of the intestinal barrier and the absence of inflammation. In conclusion, we show that Mg deficiency, independently of any other changes in nutrient intake, modulates the concentration of bifidobacteria in the gut, a phenomenon that may time-dependently affect inflammation and metabolic disorders in mice. collapse abstract
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Medicine and science in sports and exercise 2009 Aug; 41(9)
Lack of effects of creatine on the regeneration of soleus muscle after injury in rats.
PURPOSE: Creatine (Cr) supplementation may improve muscle functional capacity in patients with neuromuscular diseases, disuse atrophy, or muscular dystrophies. Activation of myogenic satellite cells has been reported to be enhanced by Cr both in vitr... expand abstracto and in vivo. Therefore, we hypothesized that Cr supplementation may improve the early steps of regeneration after muscle injury and may accelerate the recovery of both muscle mass and phenotype. METHODS: Degeneration of left soleus muscle was induced by notexin injection in rats supplemented or not with Cr. The mass of regenerated muscles was compared with contralateral intact muscles at days 1, 3, 7, 14, 21, 28, 35, and 42 after injury. We also studied protein levels of the proliferator cell nuclear antigen (PCNA) as a marker of cell proliferation, expression of myogenic regulatory factors (MRF) as a marker of differentiation, and the myosin heavy chain (MHC) profile and activities of citrate synthase (CS) and lactate dehydrogenase (LDH) isozymes as markers of muscle phenotype maturation. RESULTS: Cr supplementation accelerated the recovery of muscle Cr content during the regeneration phase. Although there were no other differences between Cr-treated and nontreated rats, we observed that 1) regenerated muscle mass remained lower than that in intact muscle mass 42 d after injury, 2) PCNA and MRF expression strongly increased in regenerated muscles, 3) the MHC profile of regenerated muscles was recovered 28 d after injury, and 4) CS activity was fully recovered from day 14, whereas the specific H isozyme of lactate dehydrogenase activity remained lower than that in intact muscles until 42 d. CONCLUSIONS: In contrast with results from in vitro studies, Cr supplementation had no effects in vivo on the time course of recovery of rat skeletal muscle mass and phenotype after notexin-induced injury. collapse abstract
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Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme 2009 May; 34(3)
Toll-like receptor signalling induced by endurance exercise.
Toll-like receptors (TLRs) are transmembrane proteins that detect a variety of molecular components mostly derived from microorganisms. TLR2 and TLR4 are amongst others present in liver, adipose tissue, and skeletal muscle. Extracellular long-chain f... expand abstractatty acids bind TLR2 and 4 and induce downstream signalling cascades implicated in cellular stress and inflammatory processes. Evidence indicates that TLR activation by non-esterified fatty acids (NEFAs) may participate in the development of insulin resistance. Exercise seems to induce a downregulation of TLR expression in various tissues, a mechanism that may take part in the protective effect of exercise against insulin resistance. Moreover, TLRs seem to mediate the activation of mitogen-activated protein kinase p38 and Jun-amino-terminal kinase by extracellular NEFAs during endurance exercise. During this type of exercise, circulating NEFAs are known to regulate the expression of various genes including pyruvate dehydrogenase kinase 4, uncoupling protein 3, carnitine palmitoyltransferase 1, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha. Whether these events are initiated by a TLR-dependent signal transduction remains to be investigated. collapse abstract
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BMC physiology 8
Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition.
BACKGROUND: There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA) depletion on hepat... expand abstractic metabolism. RESULTS: n-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol) as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPAR gamma), and an increased beta-oxidation (CPT1, PPAR alpha and PGC1 alpha) without modification of fatty acid esterification (DGAT2, GPAT1), secretion (MTTP) or intracellular transport (L-FABP). Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice. CONCLUSION: n-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between beta-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency. collapse abstract
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Current opinion in clinical nutrition and metabolic care 2008 Oct; 11(6)
Functional food for exercise performance: fact or foe?
PURPOSE OF REVIEW: To present food components showing evidence for improved sport performance in the light of the scientific literature from the past 2 years. RECENT FINDINGS: Appropriate nutrition is essential for sport performance. Nutritional prod... expand abstractucts containing carbohydrates, proteins, vitamins, and minerals have been widely used by athletes to provide something extra to the daily allowance. Currently, the field of interest is shifting from macronutrients and fluids to physiologically active isolated food components. Several of them have been demonstrated to improve sport performance at a higher level than expected with a well balanced diet. In the present review, we will focus on the benefits of creatine, caffeine, branched-chain amino acids, and more particularly leucine, beta-alanine, bicarbonate, and glycerol ingestion on exercise performance. SUMMARY: A bulk of products are sold on the market labeled with various performance benefit statements without any scientific evidence. These food components are often used without a full understanding or evaluation of the potential benefits and risks associated with their use. There is thus a real need to classify food components on the basis of their evidence-based effectiveness. collapse abstract
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Medicine and science in sports and exercise 2008 Jul; 40(8)
Fractional exhaled NO and serum pneumoproteins after swimming in a chlorinated pool.
PURPOSE: The purpose of this study was to examine whether a swimming session performed in a pool sanitized with chlorine-based agents induces lung inflammation, modifies lung epithelium permeability, and alters lung function. METHODS: Eleven voluntee... expand abstractrs performed two standardized swimming sessions: one in a nonchlorinated indoor swimming pool and the other one in a chlorinated indoor pool. Lung inflammation was assessed by fractional exhaled nitric oxide (FE(NO)). Changes in lung epithelium permeability were estimated by measuring the surfactant-associated proteins Type A and Type B (SP-A and SP-B), the Clara cell protein (CC16), and the Krebs von den Lungen-6 protein (KL-6). Lung function tests were also performed. All measurements were carried out in basal conditions, after training completion and 3 h postexercise. Nitrogen trichloride (NCl3), the most concentrated gas derived from pool water chlorination, was measured in each pool during the swimming sessions. RESULTS: NCl3 ranged from 160 to 280 microg x m(-3) in the air of the chlorinated pool and was undetectable in the nonchlorinated one. Lung function was affected neither by the exercise session nor by the type of sanitation. Serum pneumoproteins were unchanged excepted SP-A which decreased by 8% after exercise in the chlorinated pool (P < 0.05). FE(NO) increased by 34% (P < 0.05) after exercise in the nonchlorinated pool, whereas it was unaffected in the chlorinated one. CONCLUSIONS: At concentrations lower than 300 microg x m(-3), NCl3 in an indoor chlorinated pool, does not produce short-term changes in lung function or in epithelial permeability. The unchanged FE(NO) found in the chlorinated pool after exercise suggests that chlorination might inhibit NO-induced vasodilation observed during exercise. collapse abstract
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European journal of applied physiology 2008 Aug; 104(1)
Decrease in AktPKB signalling in human skeletal muscle by resistance exercise.
We analysed the effects of resistance exercise upon the phosphorylation state of proteins associated with adaptive processes from the Akt/PKB (protein kinase B) and the mitogen-activated protein kinase (MAPK) pathways. Nine healthy young men (21.7 +/... expand abstract- 0.55 year) performed 10 sets of 10 leg extensions at 80% of their 1-RM (repetition maximum). Muscle biopsies were taken from the vastus lateralis at rest, within the first 30 s after exercise and at 24 h post-exercise. Immediately post exercise, the phosphorylation states of Akt/PKB on Thr308 and Ser473 and 4E-BP1 on Thr37/46 (eukaryotic initiation factor 4E-binding protein 1) were decreased (-60 to -90%, P < 0.05). Conversely, the phosphorylation of p70(s6k) (p70 ribosomal S6 kinase) on Thr421/Ser424 was increased more than 20-fold (P < 0.05), and this was associated with a 10- to 50-fold increase in the phosphorylation of p38 and ERK1/2 (extracellular signal-regulated kinase) (P < 0.05). Twenty-four hours post-exercise the phosphorylation state of Akt/PKB on Thr308 was depressed, whereas the phosphorylation of p70(s6k) on Thr421/Ser424 and sarcoplasmic ERK1/2 were elevated. The present results indicate that high-intensity resistance exercise in the fasted state inhibits Akt/PKB and 4E-BP1 whilst concomitantly augmenting MAPK signalling and p70(s6k) on Thr421/Ser424. collapse abstract
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Journal of rehabilitation research and development 39(6)
A multistage field test of wheelchair users for evaluation of fitness and prediction of peak oxygen consumption.
An incremental multistage field test (MFT) for wheelchair users was developed to evaluate physical fitness and predict peak oxygen consumption (VO2). Using auditory feedback, the participants (n = 37) were directed to wheel around an octagonal course... expand abstract, increasing their velocity every minute until exhaustion. Wheelchair velocity and metabolic parameters were recorded with the use of a speedometer and a portable spirometer system. The average number of exercise levels performed (MFT score) was 9.17 +/- 5.81, resulting in a peak heart rate (HR) of 99.0 +/- 13.9% of the theoretical maximum. A test-retest analysis (n = 10) showed that the MFT was reliable regarding MFT score, peak VO2, and peak HR reached. Stepwise multiple regression based on individual, wheelchair, propulsion technique, and physiological parameters revealed that the MFT score was the best and only predictor of peak VO2 (mL/min/kg) (= 18.03 + 0.78 MFT score, r(2) = 0.59). The MFT assesses wheelchair mobility and estimates peak VO2 encountered during the test. collapse abstract
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Journal of applied physiology (Bethesda, Md. : 1985) 2008 Jan; 104(2)
Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle.
To test the hypothesis that creatine supplementation would enhance the anabolic responses of muscle cell signaling and gene expression to exercise, we studied nine subjects who received either creatine or a placebo (maltodextrin) for 5 days in a doub... expand abstractle-blind fashion before undergoing muscle biopsies: at rest, immediately after exercise (10 x 10 repetitions of one-leg extension at 80% 1 repetition maximum), and 24 and 72 h later (all in the morning after fasting overnight). Creatine supplementation decreased the phosphorylation state of protein kinase B (PKB) on Thr308 at rest by 60% (P < 0.05) and that of eukaryotic initiation factor 4E-binding protein on Thr37/46 (4E-BP1) by 30% 24 h postexercise (P < 0.05). Creatine increased mRNA for collagen 1 (alpha(1)), glucose transporter-4 (GLUT-4), and myosin heavy chain I at rest by 250%, 45%, and 80%, respectively, and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P < 0.05). Immediately after exercise, and independent of creatine, mRNA for muscle atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor gamma coactivator-1alpha, and interleukin-6 were upregulated (60-350%; P < 0.05); the phosphorylation state of p38 both in the sarcoplasm and nucleus were increased (12- and 25-fold, respectively; both P < 0.05). Concurrently, the phosphorylation states of PKB (Thr308) and 4E-BP1 (Thr37/46) were decreased by 50% and 75%, respectively (P < 0.05). Twenty-four hours postexercise, MAFbx, myostatin, and GLUT-4 mRNA expression decreased below preexercise values (-35 to -50%; P < 0.05); calpain 1 mRNA increased 70% 72 h postexercise (P < 0.05) and at no other time. In conclusion, 5 days of creatine supplementation do not enhance anabolic signaling but increase the expression of certain targeted genes. collapse abstract
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Journal of the International Society of Sports Nutrition 4
Comparison of new forms of creatine in raising plasma creatine levels.
ABSTRACT: BACKGROUND: Previous research has shown that plasma creatine levels are influenced by extracellular concentrations of insulin and glucose as well as by the intracellular creatine concentration. However, the form of creatine administered doe... expand abstracts not appear to have any effect although specific data on this is lacking. This study examined whether the administration of three different forms of creatine had different effects on plasma creatine concentrations and pharmacokinetics. METHODS: Six healthy subjects (three female and three male subjects) participated in the study. Each subject was assigned to ingest a single dose of isomolar amounts of creatine (4.4 g) in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr) using a balanced cross-over design. Plasma concentration curves, determined over eight hours after ingestion, were subject to pharmacokinetic analysis and primary derived data were analyzed by repeated measures ANOVA. RESULTS: Mean peak concentrations and area under the curve (AUC) were significantly higher with CrPyr (17 and 14%, respectively) in comparison to CrM and CrC. Mean peak concentration and AUC were not significantly different between CrM and CrC. Despite the higher peak concentration with CrPyr there was no difference between the estimated velocity constants of absorption (ka) or elimination (kel) between the three treatments. There was no effect of treatment with CrPyr on the plasma pyruvate concentration. CONCLUSION: The findings suggest that different forms of creatine result in slightly altered kinetics of plasma creatine absorption following ingestion of isomolar (with respect to creatine) doses of CrM, CrC and CrPyr although differences in ka could not be detected due to the small number of blood samples taken during the absorption phase. Characteristically this resulted in higher plasma concentrations of creatine with CrPyr. Differences in bioavailability are thought to be unlikely since absorption of CrM is already close to 100%. The small differences in kinetics are unlikely to have any effect on muscle creatine elevation during periods of creatine loading. collapse abstract
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Amino acids 2008 May; 35(1)
Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells.
This study compared the effects of leucine and glutamine on the mTOR pathway, on protein synthesis and on muscle-specific gene expression in myogenic C(2)C(12) cells. Leucine increased the phosphorylation state of mTOR, on both Ser2448 and Ser2481, a... expand abstractnd its downstream effectors, p70(S6k), S6 and 4E-BP1. By contrast, glutamine decreased the phosphorylation state of mTOR on Ser2448, p70(S6k) and 4E-BP1, but did not modify the phosphorylation state of mTOR on Ser2481 and S6. Whilst the phosphorylation state of the mTOR pathway is usually related to protein synthesis, the incorporation of labelled methionine/cysteine was only transiently modified by leucine and was unaltered by glutamine. However, these two amino acids affected the mRNA levels of desmin, myogenin and myosin heavy chain in a time-dependant manner. In conclusion, leucine and glutamine have opposite effects on the mTOR pathway. Moreover, they induce modification of muscle-specific gene expression, unrelated to their effects on the mTOR/p70(S6k) pathway. collapse abstract
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European journal of applied physiology 2007 Dec; 102(2)
Kinetics of creatine ingested as a food ingredient.
The aim of the present study was to test if the consumption of creatine incorporated in food bars modifies creatine plasma kinetics, erythrocyte retention and loss in urine and in feces when compared with its consumption in the form of an aqueous sol... expand abstractution (AS). Seventeen healthy young men ingested 2 g creatine either in the form of AS, or incorporated in a protein (PP)- or in a beta-glucan (BG)-rich food bar. Kinetics of plasma creatine was measured for 8-h duration and urinary excretion for 24 h. Then, the subjects received the same treatment thrice a day for 1 week at the end of which creatine contents were determined in erythrocytes and in feces (n = 4 for feces). The three crossover treatments were interspaced by a 40 +/- 1.2-day wash-out. Absorption of creatine was slowed down by 8-fold in the presence of BG (P < 0.001) and by 4-fold with PP (P < 0.001) whereas the velocity rate constant of elimination and the area under the curve were not modified. Urinary loss of creatine in the first 24 h following ingestion was 15 +/- 1.9% in AS and 14 +/- 2.2% in PP conditions (NS), whereas it was only 8 +/- 1.2% with BG (P = 0.004). Increase in creatine concentration in erythrocyte was similar in whatever form the creatine was ingested. Creatine seems to be totally absorbed since no creatine or creatinine was detectable in feces. No side effects were reported. In conclusion, ingestion of creatine combined with BG facilitates its retention by slowing down its absorption rate and reducing its urinary excretion. collapse abstract
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American journal of physiology. Cell physiology 2007 Sep; 293(4)
Creatine enhances differentiation of myogenic C2C12 cells by activating both p38 and AktPKB pathways.
In myogenic C(2)C(12) cells, 5 mM creatine increased the incorporation of labeled [(35)S]methionine into sarcoplasmic (+20%, P < 0.05) and myofibrillar proteins (+50%, P < 0.01). Creatine also promoted the fusion of myoblasts assessed by an increased... expand abstract number of nuclei incorporated within myotubes (+40%, P < 0.001). Expression of myosin heavy chain type II (+1,300%, P < 0.001), troponin T (+65%, P < 0.01), and titin (+40%, P < 0.05) was enhanced by creatine. Mannitol, taurine, and beta-alanine did not mimic the effect of creatine, ruling out an osmolarity-dependent mechanism. The addition of rapamycin, the inhibitor of mammalian target of rapamycin/70-kDa ribosomal S6 protein kinase (mTOR/p70(s6k)) pathway, and SB 202190, the inhibitor of p38, completely blocked differentiation in control cells, and creatine did not reverse this inhibition, suggesting that the mTOR/p70(s6k) and p38 pathways could be potentially involved in the effect induced by creatine on differentiation. Creatine upregulated phosphorylation of protein kinase B (Akt/PKB; +60%, P < 0.001), glycogen synthase kinase-3 (+70%, P < 0.001), and p70(s6k) (+50%, P < 0.001). Creatine also affected the phosphorylation state of p38 (-50% at 24 h and +70% at 96 h, P < 0.05) as well as the nuclear content of its downstream targets myocyte enhancer factor-2 (-55% at 48 h and +170% at 96 h, P < 0.05) and MyoD (+60%, P < 0.01). In conclusion, this study points out the involvement of the p38 and the Akt/PKB-p70(s6k) pathways in the enhanced differentiation induced by creatine in C(2)C(12) cells. collapse abstract
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Medicine and science in sports and exercise 2007 Jun; 39(7)
What do single-fiber studies tell us about exercise training?
Many exercise programs designed by trainers have the specific aim to enhance strength, endurance, or power of certain muscle groups to improve athletic performance. Muscle training is also an important component of rehabilitation to limit atrophy ass... expand abstractociated with immobilization, aging, or disease. To optimize exercise interventions, a good understanding of the response to various training programs and the identification of the mechanisms that influence muscle function are required. Changes in the performance of muscle contraction are associated, among other things, with muscle fiber-type expression and functional properties of the contractile apparatus. Chemically skinned, single fibers is the only model that allows study of the mechanical properties of human muscle fibers as a function of the expression of myosin heavy-chain isoforms. Recently, this model has been used to explore the functional adaptations after different types of solicitations. The current results of the literature indicate that cross-sectional area and force of a specific fiber type are enhanced after resistance training, whereas maximal unloaded shortening velocity is increased by endurance training. Plyometric training improves both fiber force and shortening velocity. Fiber peak power is increased after resistance or plyometric training, and on a long-term basis it is decreased after endurance training. Studies on elderly individuals indicate that this population may react differently with respect to some single-fiber adaptations after training. Generally, training regimens tend to decrease the proportion of type IIx fibers. The available data in the literature make it possible to formulate recommendations applicable to sport science and rehabilitation. collapse abstract
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International journal of sports physiology and performance 2006 Nov; 1(4)
Side effects of creatine supplementation in athletes.
CONTEXT: Allegations about side effects of creatine supplementation by athletes have been published in the popular media and scientific publications. PURPOSE: To examine the experimental evidence relating to the physiological effects of creatine supp... expand abstractlementation. RESULTS: One of the purported effects of oral creatine supplementation is increased muscle mass. A review of the literature reveals a 1.0% to 2.3% increase in body mass, which is attributed to fat-free mass and, more specifically, to skeletal-muscle mass. Although it is unlikely that water retention can completely explain these changes, increase in muscle-protein synthesis has never been observed after creatine supplementation. Indirect evidence based on mRNA analyses suggests that transcription of certain genes is enhanced. Although the effect of creatine on muscle-protein synthesis seems irrefutable according to advertising, this allegation remains under debate in the scientific literature. The kidneys appear to maintain their functionality in healthy subjects who supplement with creatine, even over several months. CONCLUSION: The authors, however, think that creatine supplementation should not be used by an individual with preexisting renal disease and that risk should be evaluated before and during any supplementation period. Even if there is a slight increase in mutagenic agents (methylamine and formaldehyde) in urine after a heavy load of creatine (20 g/day), their excretion remains within a normal range. No data are currently available regarding the potential production of heterocyclic amines with creatine supplementation. In summary, the major risk for health is probably associated with the purity of commercially available creatine. collapse abstract
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Medicine and science in sports and exercise 2006 Oct; 38(11)
Calcium sensitivity of human single muscle fibers following plyometric training.
PURPOSE: To study the effect of plyometric training on Ca2+ sensitivity and the influence of troponin T (TnT) isoforms on Ca2+ -activation properties in skinned human muscle fibers. METHODS: Biopsies were obtained from the vastus lateralis of eight m... expand abstracten before and after the training period. Chemically skinned fibers were evaluated regarding their Ca2+ -activation properties and were classified according to their myosin heavy chain (MHC) contents and analyzed regarding their slow and fast TnT isoforms. RESULTS: After training, significant improvements (P < 0.05) were found for static jump, countermovement jump, 6 x 5-m shuttle-run test, and leg-press performances. An 8% increase in the proportion of type IIa fibers (P < 0.05) was observed. Single-fiber diameters increased by 11% in type I (P < 0.01), 10% in type IIa (P < 0.001), and 15% in type IIa/IIx fibers (P < 0.001). Peak fiber force increased by 35% in type I (P < 0.001), 25% in type IIa (P < 0.001), and 57% in type IIa/IIx fibers (P < 0.01). The Ca2+ -activation threshold was not altered by training, but the Ca2+ concentration required to elicit half-maximal activation showed a decreasing trend, with significant changes in type I fibers (P < 0.001). Cooperativity at low Ca2+ concentrations was increased in type I and type IIa/IIx fibers (P < 0.05). Type I fibers exclusively expressed slow TnT isoforms, and type II fibers were always associated with fast TnT isoforms, independent of training status. Therefore, changes in Ca2+ sensitivity after training could not be explained by differential fast or slow TnT isoform expression. CONCLUSION: Plyometric training increased single-fiber Ca2+ sensitivity, especially in type I fibers. These changes could not be explained by a modified TnT isoform expression pattern. collapse abstract
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Journal of applied physiology (Bethesda, Md. : 1985) 2006 Dec; 102(1)
Effect of long-term muscle paralysis on human single fiber mechanics.
This study compared human muscles following long-term reduced neuromuscular activity to those with normal functioning regarding single fiber properties. Biopsies were obtained from the vastus lateralis of 5 individuals with chronic (>3 yr) spinal cor... expand abstractd injury (SCI) and 10 able-bodied controls (CTRL). Chemically skinned fibers were tested for active and passive mechanical characteristics and subsequently classified according to myosin heavy chain (MHC) content. SCI individuals had smaller proportions of type I (11 +/- 7 vs. 34 +/- 5%) and IIa fibers (11 +/- 6 vs. 31 +/- 5%), whereas type IIx fibers were more frequent (40 +/- 13 vs. 7 +/- 3%) compared with CTRL subjects (P < 0.05). Cross-sectional area and peak force were similar in both groups for all fiber types. Unloaded shortening velocity of fibers from paralyzed muscles was higher in type IIa, IIa/IIx, and IIx fibers (26, 65, and 47%, respectively; P < 0.01). Consequently, absolute peak power was greater in type IIa (46%; P < 0.05) and IIa/IIx fibers (118%; P < 0.01) of the SCI group, whereas normalized peak power was higher in type IIa/IIx fibers (71%; P < 0.001). Ca(2+) sensitivity and passive fiber characteristics were not different between the two groups in any fiber type. Composite values (average value across all fibers analyzed within each study participant) showed similar results for cross-sectional area and peak force, whereas maximal contraction velocity and fiber power were more than 100% greater in SCI individuals. These data illustrate that contractile performance is preserved or even higher in the remaining fibers of human muscles following reduced neuromuscular activity. collapse abstract
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Journal of applied physiology (Bethesda, Md. : 1985) 2006 Feb; 100(3)
Stretch-shortening cycle exercises: an effective training paradigm to enhance power output of human single muscle fibers.
Functional performance of lower limb muscles and contractile properties of chemically skinned single muscle fibers were evaluated before and after 8 wk of maximal effort stretch-shortening cycle (SSC) exercise training. Muscle biopsies were obtained ... expand abstractfrom the vastus lateralis of eight men before and after the training period. Fibers were evaluated regarding their mechanical properties and subsequently classified according to their myosin heavy chain content (SDS-PAGE). After training, maximal leg extensor muscle force and vertical jump performance were improved 12% (P<0.01) and 13% (P<0.001), respectively. Single-fiber cross-sectional area increased 23% in type I (P<0.01), 22% in type IIa (P<0.001), and 30% in type IIa/IIx fibers (P<0.001). Peak force increased 19% in type I (P<0.01), 15% in type IIa (P<0.001), and 16% in type IIa/IIx fibers (P<0.001). When peak force was normalized with cross-sectional area, no changes were found for any fiber type. Maximal shortening velocity was increased 18, 29, and 22% in type I, IIa, and hybrid IIa/IIx fibers, respectively (P<0.001). Peak power was enhanced in all fiber types, and normalized peak power improved 9% in type IIa fibers (P<0.05). Fiber tension on passive stretch increased in IIa/IIx fibers only (P<0.05). In conclusion, short-term SSC exercise training enhanced single-fiber contraction performance via force and contraction velocity in type I, IIa, and IIa/IIx fibers. These results suggest that SSC exercises are an effective training approach to improve fiber force, contraction velocity, and therefore power. collapse abstract
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Journal of applied physiology (Bethesda, Md. : 1985) 2006 Feb; 100(3)
On the modeling of breath-by-breath oxygen uptake kinetics at the onset of high-intensity exercises: simulated annealing vs. GRG2 method.
Modeling in the time domain, the non-steady-state O2 uptake on-kinetics of high-intensity exercises with empirical models is commonly performed with gradient-descent-based methods. However, these procedures may impair the confidence of the parameter ... expand abstractestimation when the modeling functions are not continuously differentiable and when the estimation corresponds to an ill-posed problem. To cope with these problems, an implementation of simulated annealing (SA) methods was compared with the GRG2 algorithm (a gradient-descent method known for its robustness). Forty simulated Vo2 on-responses were generated to mimic the real time course for transitions from light- to high-intensity exercises, with a signal-to-noise ratio equal to 20 dB. They were modeled twice with a discontinuous double-exponential function using both estimation methods. GRG2 significantly biased two estimated kinetic parameters of the first exponential (the time delay td1 and the time constant tau1) and impaired the precision (i.e., standard deviation) of the baseline A0, td1, and tau1 compared with SA. SA significantly improved the precision of the three parameters of the second exponential (the asymptotic increment A2, the time delay td2, and the time constant tau2). Nevertheless, td2 was significantly biased by both procedures, and the large confidence intervals of the whole second component parameters limit their interpretation. To compare both algorithms on experimental data, 26 subjects each performed two transitions from 80 W to 80% maximal O2 uptake on a cycle ergometer and O2 uptake was measured breath by breath. More than 88% of the kinetic parameter estimations done with the SA algorithm produced the lowest residual sum of squares between the experimental data points and the model. Repeatability coefficients were better with GRG2 for A1 although better with SA for A2 and tau2. Our results demonstrate that the implementation of SA improves significantly the estimation of most of these kinetic parameters, but a large inaccuracy remains in estimating the parameter values of the second exponential. collapse abstract
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Medicine and science in sports and exercise 2005 Sep; 37(10)
Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate.
PURPOSE: It has been claimed that oral creatine supplementation might have potential cytotoxic effects on healthy consumers by increasing the production of methylamine and formaldehyde. Despite this allegation, there has been no scientific evidence o... expand abstractbtained in humans to sustain or disprove such a detrimental effect of this widely used ergogenic substance. METHODS: Twenty young healthy men ingested 21 g of creatine monohydrate daily for 14 consecutive days. Venous blood samples and 24-h urine were collected before and after the 14th day of supplementation. Creatine and creatinine were analyzed in plasma and urine, and methylamine, formaldehyde, and formate were determined in 24-h urine samples. RESULTS: Oral creatine supplementation increased plasma creatine content 7.2-fold (P < 0.001) and urine output 141-fold (P < 0.001) with no effect on creatinine levels. Twenty-four-hour urine excretion of methylamine and formaldehyde increased, respectively, 9.2-fold (P = 0.001) and 4.5-fold (P = 0.002) after creatine feeding, with no increase in urinary albumin output (9.78 +/- 1.93 mg x 24 h(-1) before, 6.97 +/- 1.15 mg x 24 h(-1) creatine feeding). CONCLUSION: This investigation shows that short-term, high-dose oral creatine supplementation enhances the excretion of potential cytotoxic compounds, but does not have any detrimental effects on kidney permeability. This provides indirect evidence of the absence of microangiopathy in renal glomeruli. collapse abstract
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Medicine and science in sports and exercise 2005 Apr; 37(5)
Increased IGF mRNA in human skeletal muscle after creatine supplementation.
PURPOSE: We hypothesized that creatine supplementation would facilitate muscle anabolism by increasing the expression of growth factors and the phosphorylation of anabolic signaling molecules; we therefore tested the responses of mRNA for IGF-I and I... expand abstractGF-II and the phosphorylation state of components of anabolic signaling pathways p70(s6k) and 4E-BP1 to a bout of high-intensity resistance exercise after 5 d of creatine supplementation. METHODS: In a double-blind cross-over design, muscle biopsies were taken from the m. vastus lateralis at rest and 3 and 24 h postexercise in subjects who had taken creatine or placebo for 5 d (21 g x d(-1)). For the first 3 h postexercise, the subjects were fed with a drink containing maltodextrin (0.3 g x kg(-1) body weight x h(-1)) and protein (0.08 g x kg(-1) body weight x h(-1)). RESULTS: After creatine supplementation, resting muscle expressed more mRNA for IGF-I (+30%, P < 0.05) and IGF-II (+40%, P = 0.054). Exercise caused an increase by 3 h postexercise in IGF-I (+24%, P < 0.05) and IGF-II (+48%, P < 0.05) and by 24 h postexercise in IGF-I (+29%, P < 0.05), but this effect was not potentiated by creatine supplementation. The phosphorylation states of p70(s6k) and 4E-BP1 were not affected by creatine at rest; phosphorylation of both increased (150-400%, P < 0.05) to similar levels under placebo and creatine conditions at 3 h postexercise plus feeding. However, the phosphorylation state of 4E-BP1 was higher in the creatine versus placebo condition at 24 h postexercise. CONCLUSION: The increase in lean body mass often reported after creatine supplementation could be mediated by signaling pathway(s) involving IGF and 4E-BP1. collapse abstract
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European journal of applied physiology 2005 Apr; 94(1-2)
Regulation of mTOR by amino acids and resistance exercise in skeletal muscle.
Resistance exercise disturbs skeletal muscle homeostasis leading to activation of catabolic and anabolic processes within the muscle cell. A current challenge of exercise biology is to describe the molecular mechanisms of regulation by which contract... expand abstractile activity stimulates net protein breakdown during exercise and net protein synthesis during recovery. Muscle growth is optimized by combining exercise and appropriate nutritional strategies, such as amino acid (AA) and carbohydrate ingestion. The effects are integrated at the level of one central regulatory protein, mTOR (mammalian target of rapamycin). mTOR is a complex protein integrating signals of the energetic status of the cell and environmental stimuli to control protein synthesis, protein breakdown and therefore cell growth. mTOR is known to be activated by insulin, and the mechanisms involved are well documented. The ways by which exercise and AA lead to mTOR activation remain partially unclear. Exercise and AA use different signalling pathways upstream of mTOR. Exercise seems to recruit partially the same pathway as insulin, whereas AA could act more directly on mTOR. During resistance exercise, the activity of mTOR could be acutely blunted by AMP-activated protein kinase (AMPK), thus inhibiting protein synthesis and enhancing AA availability for energy metabolism. During recovery, the inhibition of mTOR by AMPK is suppressed, and its activation is maximized by the presence of AA. There appears to be a requirement for a minimal concentration of plasma insulin to stimulate muscle protein synthesis in response to resistance exercise and AA ingestion. collapse abstract
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Muscle & nerve 2004 Apr; 29(5)
Effect of creatine supplementation on skeletal muscle of mdx mice.
Dystrophic mice (mdx) and their controls (C57/Bl10) were fed for 1 month with a diet with or without creatine (Cr) enrichment. Cr supplementation reduced mass (by 19%, P < 0.01) and mean fiber surface (by 25%, P < 0.05) of fast-twitch mdx muscles. In... expand abstract both strains, tetanic tension increased slightly (9.2%) without reaching statistical significance (P = 0.08), and relaxation time increased by 16% (P < 0.001). However, Cr had no protective effect on the other hallmarks of dystrophy such as susceptibility to eccentric contractions; large numbers of centrally nucleated fibers in tibialis anterior; and elevated total calcium content, which increased by 85% (P = 0.008) in gastrocnemius mdx muscles. In conclusion, Cr may be a positive intervention for improving function of dystrophic muscle. collapse abstract
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FEBS letters 2004 Jan; 557(1-3)
Creatine increases IGF-I and myogenic regulatory factor mRNA in C(2)C(12) cells.
Addition of creatine to the differentiation medium of C(2)C(12) cells leads to hypertrophy of the myotubes. To investigate the implication of insulin-like growth factor I (IGF-I) and myogenic regulatory factors (MRFs) in this hypertrophy, their mRNA ... expand abstractlevels were assessed during the first 72 h of differentiation. Creatine significantly increased the IGF-I mRNA level over the whole investigated period of time, whereas the MRF mRNA levels were only augmented at precise moments, suggesting a general activation mechanism for IGF-I and a specifically regulated mechanism for MRF transcription. Our results suggest therefore that creatine-induced hypertrophy of C(2)C(12) cells is at least partially mediated by overexpression of IGF-I and MRFs. collapse abstract
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