Abstract: 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 vitro 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.
Abstract: 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 fatty 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.
Abstract: 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 double-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.
Abstract: 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, and 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.
Abstract: 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 +/- 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.
Abstract: 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 solution (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.
Abstract: 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 volunteers 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.
Abstract: 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 hepatic 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.
Abstract: 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 products 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.
Abstract: 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 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.
Abstract: 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 cord 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.
Abstract: 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 associated 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.
Abstract: 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 does 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.
Abstract: 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 estimation 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.
Abstract: 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 from 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.
Abstract: 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 supplementation. 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.
Abstract: 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 men 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.
Abstract: 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 IGF-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.
Abstract: 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 contractile 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.
Abstract: 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 obtained 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.
Abstract: 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 levels 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.
Abstract: 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 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.
Abstract: Dietary creatine supplementation is associated with increases in muscle mass, but the mechanism is unknown. We tested the hypothesis that creatine supplementation enhanced myofibrillar protein synthesis (MPS) and diminished muscle protein breakdown (MPB) in the fed state. Six healthy men (26 +/- 7 yr, body mass index 22 +/- 4 kg/m(2)) were studied twice, 2-4 wk apart, before and after ingestion of creatine (21 g/day, 5 days). We carried out two sets of measurements within 5.5 h of both MPS (by incorporation of [1-(13)C]leucine in quadriceps muscle) and MPB (as dilution of [1-(13)C]leucine or [(2)H(5)]phenylalanine across the forearm); for the first 3 h, the subjects were postabsorptive but thereafter were fed orally (0.3 g maltodextrin and 0.083 g protein. kg body wt(-1) x h(-1)). Creatine supplementation increased muscle total creatine by approximately 30% (P < 0.01). Feeding had significant effects, doubling MPS (P < 0.001) and depressing MPB by approximately 40% (P < 0.026), but creatine had no effect on turnover in the postabsorptive or fed states. Thus any increase in muscle mass accompanying creatine supplementation must be associated with increased physical activity.
Abstract: Muscle hypertrophy during resistance training is reportedly increased by creatine supplementation. Having previously failed to find an anabolic effect on muscle protein turnover at rest, either fed or fasted, we have now examined the possibility of a stimulatory effect of creatine in conjunction with acute resistance exercise. Seven healthy men (body mass index, 23 +/- 2 kg/m2, 21 +/- 1 yr, means +/- SE) performed 20 x 10 repetitions of leg extension-flexion at 75% one-repetition maximum in one leg, on two occasions, 4 wk apart, before and after ingesting 21 g/day creatine for 5 days. The subjects ate approximately 21 g maltodextrin + 6 g protein/h for 3 h postexercise. We measured incorporation of [1-13C]leucine into quadriceps muscle proteins in the rested and exercised legs. Leg protein breakdown (as dilution of [2H5]phenylalanine) was also assessed in the exercised and rested leg postexercise. Creatine supplementation increased muscle total creatine by approximately 21% (P < 0.01). Exercise increased the synthetic rates of myofibrillar and sarcoplasmic proteins by two- to threefold (P < 0.05), and leg phenylalanine balance became more positive, but creatine was without any anabolic effect.
Abstract: The effect of creatine (Cr) supplementation on muscle function and body composition of 12 boys with Duchenne muscular dystrophy and three with Becker dystrophy was evaluated by a randomized double-blind cross-over study (3 g Cr or maltodextrin daily for 3 months, with wash-out period of 2 months). After placebo, no change was observed in maximal voluntary contraction (MVC) and resistance to fatigue, whereas total joint stiffness (TJS) was increased by approximately 25% (P < 0.05). The patients receiving Cr did not show any change in TJS, improved MVC by 15% (P = 0.02), and almost doubled their resistance to fatigue (P < 0.001). In patients still independent of a wheelchair (n = 5), bone mineral density increased by 3% (P < 0.05), and urinary excretion of collagen type I cross-linking N-telopeptide declined to about one third (P < 0.001) after Cr. No adverse effect was observed. Thus, Cr may provide some symptomatic benefit in these patients.
Abstract: 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, 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.
Abstract: Taurine is released by contracting muscles, but its actual role remains unspecified. In this study, we investigated whether the exercise-stimulated release of taurine from muscle into the plasma regulates the modification of osmolality induced by intramuscular osmolyte production. Six subjects performed 90 min of cycling exercise (at 70% maximum power output) on two occasions, with (HC) or without (DC) fluid intake. Taurine content was determined in plasma, blood cells and urine before and after the endurance events, together with plasma osmolality. Plasma osmolality increased by 4% in the DC experiment ( P<0.01), but remained stable in the HC condition. The exercise also induced changes in the mean (SD) plasma taurine content to a greater degree in HC [+63 (26)%] than in DC [+33 (18)%; P<0.05], supporting the hypothesis that taurine is released into the plasma via an osmoregulatory process. However, the higher plasma taurine content in HC was not related to changes in renal taurine. In addition, the increase of taurine in plasma was not related to its release from blood cells since their taurine concentration increased by 70% both in HC [429 (77) to 680 (82) microM; P=0.003] and in DC [451 (57) to 731 (34) microM; P<0.001]. The lack of correlation between plasma volume modification and the mass ratio of taurine would exclude a major role for taurine exchange in plasma volume regulation. Sodium ( R=0.967, P<0.001), chloride ( R=0.917, P<0.001) and osmolality ( R=0.924, P<0.001) seem to be the main regulators of plasma volume changes during exercise. In conclusion, changes in the plasma taurine content during endurance exercise is related to an osmoregulatory process, but this alone does not control plasma volume changes.
Abstract: Nitrogen trichloride (NCl(3)) is an irritant gas released in the air of indoor pools sanitized with chlorine-based disinfectants. In the present study we investigated the effects of NCl(3) on the pulmonary epithelium of pool attendees by measuring the leakage into serum of three lung-specific proteins (pneumoproteins): the alveolar surfactant-associated proteins A and B (SP-A and SP-B) and the bronchiolar 16 kDa Clara cell protein (CC16). These pneumoproteins were measured in the serum of 29 recreational swimmers (16 children and 13 adults) before and after attending a chlorinated pool with a mean NCl(3) concentration of 490 microg m(-3). Pneumoprotein changes in serum were also studied in 14 trained swimmers performing an intensive 45 min standardized swimming session in a chlorinated pool (mean NCl(3) concentration of 355 microg m(-3)) and for the purposes of comparison in a non-chlorinated pool sanitized by the copper/silver method. Serum CC16 was not increased in recreational swimmers, but in trained swimmers serum levels of this protein peaked immediately after strenuous exercise, both in the copper/silver pool and in the chlorinated pool. This acute increase in airway permeability is probably the consequence of the mechanical stress on the epithelial barrier caused by overinflation and/or hyperventilation during intense exercise. Serum levels of SP-A and SP-B were unaffected by strenuous exercise in the copper/silver pool. The two proteins were, however, significantly increased in a time-dependent manner in recreational and trained swimmers attending the chlorinated pool. The intravascular leakage of SP-A and SP-B was already statistically significant after only 1 h of exposure to pool air without exercising and remained elevated for 12 h after. These changes were not associated with decrements in lung function. The ability of NCl(3) to acutely disrupt the lung epithelium barrier was confirmed in mice using serum CC16 and plasma proteins in bronchoalveolar lavage fluid as permeability markers. The significance of these permeability changes induced by NCl(3) in the deep lung is presently unknown. In view of the increasing and widespread human exposure to this gas not only in indoor pools but also in a variety of other situations, these findings warrant further study.
Abstract: The purpose of this study was to analyse lower leg skin blood flow (laser Doppler flowmetry) in five individuals with high-level paraplegia (T5-T9), six participants with low-level paraplegia (T10-T12) and six able-bodied controls during 3-minute light and heavy arm-cranking exercises (approximately 15% and 80% peak power output, respectively). Throughout light exercise, cutaneous vasoconstriction was shown for the control group (-20%), but not the low-level (+62%) or the high-level paraplegic group (+33%). During heavy exercise, vasoconstriction was initially found for controls followed by an increase in skin blood flow during the last 2 minutes, whereas the participants with paraplegia demonstrated skin blood flow increases. Skin blood flow responses were not related to lesion level. Metabolic parameters were not different among the three groups, but heart rates for participants with paraplegia were higher during heavy exercise than in controls. These results suggest impaired sympathetic vasoconstriction in individuals with paraplegia during exercise.
Abstract: This study investigated whether a 60-minute arm-cranking exercise at 50% of the individual maximal power output would increase lower limb skin blood flow (laser Doppler flowmetry) in individuals with high-level (T5-T9; n = 6) and low-level paraplegia (T10-T12; n = 6), compared to 6 able-bodied controls. Significant (P < 0.05) group by time interactions (two-way repeated measures ANOVA) were found for leg cutaneous vascular conductance, leg skin temperature and esophageal temperature. Cutaneous vascular conductance increased to a peak of approximately 180% of pre-exercise rest in both paraplegic groups and to -436% in the control group, with differences after 15, 30, 45 and 60 minutes of exercise. Leg skin temperature increased by approximately 0.3 C in individuals with paraplegia and decreased by approximately 2.0 C in able-bodied. Esophageal temperature increases at the end of exercise were higher in individuals with paraplegia (approximately 0.9 C) than in able-bodied subjects (approximately 0.5 C). Heart rate was higher in the paraplegic groups than in able-bodied, whilst stroke volume and cardiac output were not different (impedance cardiography). The data suggest that lesion level had no influence on the results. These findings indicate that there is no excessive shunting of blood to the skin of the lower limbs of individuals with paraplegia during sustained exercise.
Abstract: Changes in urinary and plasma taurine and amino acids have been evaluated in trained runners competing in the Rotterdam Marathon, 1998, both immediately after completing the event and 24h after recovery. There were significant changes in the urinary amino acids excretion, the majority showing a significant decrease both immediately at the completion of the Marathon and after 24h recovery. In contrast urinary taurine excretion increased immediately post Marathon, although not significantly as the range of results was wide. Such changes in urinary taurine correlated with percentage changes in plasma creatine kinase both immediately post race, (r = 0.972, P < 0.001), and 24h later (r = 0.872, P < 0.001), possibly indicating that the source of the taurine was muscle. Significant correlations between the individual values for urinary and plasma amino acids in all of the athletes were calculated for taurine (r = 0.528), glycine (r = 0.853), threonine (r = 0.749), alanine (r = 0.747), serine (r = 0.620), glutamine (0.614), arginine (r = 0.507), histidine (r = 0.470) and valine (r = 0.486). Changes in the mean plasma concentrations of amino acids were comparable to our previously published data (Ward et al., 1999) the majority showing significant decreases immediately and 24h post Marathon, such an adaptation being due primarily to their utilisation for gluconeogenesis. However, in contrast, the mean taurine concentrations were significantly elevated both post race, P < 0.01 and after 24h, P < 0.05. The physiological response by the muscle to exhaustive exercise, particularly with regard to changes in plasma and urinary taurine concentrations remain to be elucidated, but is probably related to muscle function impairment. The increase in taurine urinary excretion could be used as an indicator of muscle damage occurring during exhaustive exercise. Whether taurine supplementation would minimise such changes is an interesting scientific question and merits investigation.
Abstract: The veno-arteriolar reflex (VAR) in spinal-cord-injured subjects (SCI) has been attributed little interest, although it might contribute substantially to their blood redistribution. This peripheral reflex response, which is based on an axon reflex, consists of a reduction in limb blood flow following an increase in venal transmural pressure. The purpose of the present investigation was to assess the peripheral and central cardiovascular adaptations of paraplegics with high (HP) and low (LP) spinal lesions to subsequent, passive posture changes involving leg dependency and upright sitting, and to compare them to able-bodied (AB) subjects. Lower-limb cutaneous vascular conductance (CVC) was evaluated from skin blood flow measurements (laser Doppler flowmetry) taken from the dorsal foot, and from ankle blood pressure. Cardiac stroke volume, heart rate and myocardial performance were assessed using impedance cardiography and brachial blood pressure. During leg dependency, a significant vasoconstriction was noted in all three groups. The initial decrease in CVC was higher in HP (-76.82%) than in AB (-45.82%), the values for LP (-67.08%) lying in between these two (significant group x time interaction: F = 2.832; P = 0.042). There were no differences for parameters of central hemodynamics. No between-group differences were noted in any parameter tested during upright sitting. CVC remained at a similar low level as compared to leg dependency, stroke volume decreased, heart rate and blood pressure increased, and myocardial performance remained constant. The present results suggest that paraplegics have a peripheral VAR in their paralyzed lower limbs, and that this contributes to their cardiovascular stability.
Abstract: 31P NMR was used to assess the influence of two weeks creatine supplementation (21g x d(-1)) on resting muscle PCr concentration, on the rate of PCr repletion (R(depl)), and on the half-time of PCr repletion (t 1/2). Body mass (BM) and volume of body water compartments were also estimated by impedance spectroscopy. Fourteen healthy male subjects (20.8+/-1.9 y) participated in this double-blind study. PCr was measured using a surface coil placed under the calf muscle, at rest and during two exercise bout the duration of which was 1 min. They were interspaced by a recovery of 10 min. The exercises comprised of 50 plantar flexions-extensions against weights corresponding to 40% and 70% of maximal voluntary contraction (MVC), respectively. Creatine supplementation increased resting muscle PCr content by approximately 20% (P= 0.002). R(depl) was also increased by approximately 15% (P< 0.001) and approximately 10% (P = 0.026) during 40% and 70% MVC exercises, respectively. No change was observed in R(repl) and t1/2. BM and body water compartments were not influenced. These results indicate that during a standardized exercise more ATP is synthesized by the CK reaction when the pre-exercise level in PCr is higher, giving some support to the positive effects recorded on muscle performance.
Abstract: The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.
Abstract: Guanidinoethane sulfonic acid (GES), a chemical and biological analog of taurine, decreases rat muscle taurine content when added to drinking water. Over the same period, GES appears in muscle. GES supplementation is often used to study the effect of taurine depletion on physiological mechanisms, without taking into account the possible actions of GES. The purpose of the present study was to investigate the specific actions of GES on contraction of skeletal muscle. In mice EDL muscle, the time delay needed to observe a 20% force decrease after the end of a tetanic stimulation was higher in GES-supplemented than in control muscle. This observation in GES-supplemented muscle could be explained by the action of taurine or GES on several targets, beside others the rate of Ca2+ uptake by sarcoplasmic reticulum (SR) and the Ca2+ sensitivity of myofilaments. SR of rat EDL was isolated by successive centrifugations. The effect of 20 mM taurine or GES on the rate of Ca2+ uptake by SR was measured with the fluorescent Ca2+ indicator fura-2. The results show that the rate of Ca2+ uptake by SR is not modified in the presence of taurine or GES. The Ca2+ sensitivity of myofilaments was studied in chemically skinned fibers in the presence of 20 mM taurine or GES. Both taurine and GES increased the myofilament sensitivity to Ca2+. Thus, the prolonged relaxation time of GES-supplemented muscle can be attributed to an increase in myofilament sensitivity to Ca2+. This higher sensitivity is not due to a decrease in muscle taurine content but rather to an increased GES concentration.
Abstract: difference, P<0.05). The paraplegics developed a higher esophageal and leg skin temperature, which was attributed to the lack of active vasodilation and evaporative cooling over the legs. The results indicate that individuals with paraplegia suffer from impaired cutaneous vasoconstriction at the onset of arm exercise, and possess only a limited vasodilatory capability in the paralyzed regions. During intense exercise, thermoregulation depends critically on active cutaneous vasodilation and skin cooling.
Abstract: The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is performed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.
Abstract: The purpose of this study was to test the effect of creatine supplement on the size of the extra- and intracellular compartments and on the increase of isokinetic force during a strength training-program. Twenty-five healthy male subjects (age 22.0+/-2.9 years) participated in this experiment. Seven subjects formed the control-group. They did not complete any training and did not have any dietary supplement. The eighteen other subjects were randomly divided into a creatine- (n = 8) and a placebo-group (n = 10). They were submitted to a controlled strength-training program for 42 days followed by a detraining period of 21 days. Creatine and placebo were given over a period of 9 weeks. The size of the body water compartments was assessed by bioimpedance spectroscopy and the isokinetic force was determined during a single squat by means of an isokinetic dynamometer. These measurements were completed beforehand, at the end of the training period, and after the determining period. Both placebo- and creatine-group increased the isokinetic force by about 6% after the training period, showing that creatine ingestion does not induce a higher increase of the force measured during a single movement. No change in body mass was observed in the control- and placebo-groups during the entire experiment period while the body mass of the creatine-group was increased by 2 kg (P < 0.001). This change can be attributed partially to an increase (P = 0.039) in the body water content (+1.11), and more specifically, to an increase (P < 0.001) in the volume of the inter-cellular compartment (+0.61). Nevertheless, the relative volumes of the body water compartments remained constant and therefore the gain in body mass cannot be attributed to water retention, but probably to dry matter growth accompanied with a normal water volume.
Abstract: PURPOSE: Oral creatine supplementation is widely used in sportsmen and women. Side effects have been postulated, but no thorough investigations have been conducted to support these assertions. It is important to know whether long-term oral creatine supplementation has any detrimental effects on kidney function in healthy population. METHODS: Creatinine, urea, and plasma albumin clearances have been determined in oral creatine consumers (10 months to 5 yr) and in a control group. RESULTS: There were no statistical differences between the control group and the creatine consumer group for plasma contents and urine excretion rates for creatinine, urea, and albumin. Clearance of these compounds did not differ between the two groups. Thus, glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups. CONCLUSIONS: Neither short-term, medium-term, nor long-term oral creatine supplements induce detrimental effects on the kidney of healthy individuals.
Abstract: PURPOSE: A new ensemble-averaging (EA) approach was developed with the goal of investigating central hemodynamics by transthoracic impedance cardiography during maximal arm cranking. This EA procedure of the first time derivative of impedance changes (dZ/dt) over several cardiac cycles differs from previously reported techniques with respect to cycle selection strategy, according to fixed criteria, and processing methods. METHODS: First, the primary elements of the Kubicek stroke volume (SV) formula, as determined by EA, were compared with the values determined by the standard hand-processing (HP) method over a large range of cardiac outputs. RESULTS: Results showed a very high reliability for ventricular ejection time (r = 0.996), (dZ/dt)min (r = 0.995), SV (r = 0.977), and heart rate (r = 0.999). Second, the EA procedure was applied to six subjects performing a continuous, multistage arm cranking test to volitional fatigue. The present technique allowed for an effective filtering of movement and breathing artifacts of the original signal. Thus, interpretation of the dZ/dt wave form was convenient, even at maximal arm cranking power outputs up to 120 W. Stroke volume ranged from 63.83 to 127.18 mL.beat-1, showing no significant variations with oxygen consumption. Cardiac output increased linearly with oxygen uptake, reaching a mean maximal value of 16 L.min-1. CONCLUSION: The present procedure opens a new field of application to impedance cardiography, permitting to measure cardiac output during maximal arm cranking exercise.
Abstract: The hypothesis of magnesium deficiency in isoproterenol (ISO) induced myocardial injury has been investigated by 31P nuclear magnetic resonance spectroscopy. High energy phosphate concentrations, pHi, and intracellular free magnesium concentration ([Mg2+]i) were measured in isolated rabbit hearts perfused at constant flow and subjected to 10(-6)M isoproterenol during 30 min. Recent calibrations were used for [Mg2+]i measurements, and uncertainties on [Mg2+]i estimated values were calculated. During isoproterenol infusion, pHi, [PCr], and [ATP] decreased, while [P(i)] increased. When it was stopped, [PCr] completely repleted, whereas only a partial restoration was observed for pHi and [P(i)]. A rise of end-diastolic pressure and perfusion pressure expressed a contracture, concomitant with a lack of [ATP] recovery, which remained at 59 +/- 13% of the rest value. These results establish that 10(-6) M isoproterenol caused severe myocardial injury. [Mg2+]i increased from 0.70 mM at rest to 0.88 mM at the end of the isoproterenol period. Considering the estimated uncertainties on the [Mg2+]i values, this increase was not significant. After isoproterenol infusion, [Mg2+]i progressively decreased to reach 0.72 mM at 45 min recovery. It is concluded that isoproterenol myocardial toxicity may not be related to [Mg2+]i deficiency.
Abstract: The purpose of this study was to develop an original friction loaded ergometer allowing measurement of the resisting torque (Mb) and the angular velocity (omega) by means of a force transducer and an optical pick-up during all-out arm cranking exercises. Taking into account the kinetic energy variations of the flywheel, the peak power developed at the crank (P(c)peak) and the peak angular velocity (omegapeak) were determined in 6 male and 6 female able-bodied subjects during 6-8 bouts of 3 s duration, performed at maximal velocity, with Mb varying from 0.07 to 0.87 Nm x kg(-1). In each subject, the Mb increase was related to a decrease of omegapeak. This relationship was expressed through a negative linear regression (0.92 < R2 < 0.99) for omegapeak between 13 and 28 rad x s(-1) for the males and 10 and 24 rad x s(-1) for the females. The relationship between P(c)peak and Mb did not fit well for all subjects (0.01 < R2 < 0.93) with a parabolic equation, indicating that for upper limb testing, the maximal power should be defined as the highest power measured during several bouts performed with appropriate resisting torque. The present study also demonstrated the importance of taking into account the inertia of the moving flywheel during the acceleration phase of an all-out arm crank exercise, when determining the peak power output.
Abstract: The creatine kinase reaction has been studied by 31P NMR in exercising human calf muscle. Quantitative analysis of high energy phosphates and saturation transfer study of the creatine kinase flux in the direction of ATP synthesis (Vfor) were performed at rest and during exercise. As expected, exercise induced a [PCr] decrease (from 28.5 +/- 0.9 to 21.9 +/- 1.5 mM, P < 0.01) matched by a Pi increase (from 4.5 +/- 0.2 to 8.9 +/- 1.8 mM, P = 0.06). pHi and [ATP] remained unchanged. Vfor did not change from rest (12.4 +/- 0.9 mM s(-1)) to moderate exercise and decreased at the highest exercise level (8.4 +/- 1.4 mM s(-1), P = 0.006). This observation differs from the prediction of the creatine kinase rate equation, showing an increase in the flux with exercise intensity. Computations suggest that this discrepancy arises from metabolite compartmentalization and/or from the reaction kinetics of a dead end complex stabilized by planar anions.
Abstract: This study presents a mathematical model by which power output (PO) delivered to the rear wheel during handrim wheelchair propulsion on a roller ergometer can be determined for individual wheelchair-user combinations. PO is calculated from the torque applied to the wheel and its angular velocity. The torque applied is a function of one total internal torque of the wheelchair-ergometer system, the rotational moment of inertia of the rear wheel, the one of the roller and its angular acceleration. The total internal torque reflects all internal friction forces and is determined with a deceleration test. To assess the reliability of this approach, 11 able-bodied subjects underwent progressively increasing exercise tests on two different occasions. PO values ranged from 12 to 63 W and were highly reliable (r2 > 0.95). Peak physiological responses were never different from test 1 and 2 (repeated measures ANOVA; p: N.S.) and correlations were 0.90, 0.72, 0.88, 0.82, 0.70 and 0.85 for PO, oxygen uptake (VO2), heart rate, minute ventilation, carbon dioxide production and blood lactate concentration, respectively. After an initial increase, gross mechanical efficiency dropped at higher velocities, with values ranging from 4.64 to 11.26%. In conclusion, the roller ergometer, the mathematical model to determine PO and the protocol used seem to be adequate to exercise test people in a handrim wheelchair. It is feasible to apply the theoretical procedure to other roller ergometers which would allow for comparisons of exercise intensities and protocols between different devices used in exercise physiology and rehabilitation.
Abstract: Tracers have been used extensively to study lactate metabolism in humans during rest and exercise. Nevertheless, quantification of in vivo lactate kinetics as measured by lactate tracers remains controversial and new data are necessary to clarify the issue. The present study has developed a simple kinetic model which does not require labelled molecules and which yields proportional and quantitative information on lactate metabolism in humans during postexercise recovery performed at different levels of intensity. Five subjects took part in six experiments each of which began with the same strenuous exercise (StrEx; 1 min, 385 W, 110 rpm). The StrEx of each session was followed by a different intensity of recovery: passive recovery (PR) and active recoveries (AR) with power outputs of 60, 90, 120, 150 and 180 W, respectively. Blood lactate concentration was measured prior to and immediately after StrEX and regularly during the 1st h of recovery. Oxygen uptake (VO2) was measured every 30 s during the whole session. The results showed that the disappearance rate constant (ke) increases abruptly from PR [0.080 (SEM 0.004) min-1] to moderate AR [60 W: 0.189 (SEM 0.039) min-1] and decreases slowly during more intense AR [180 W: 0.125 (SEM 0.027) min-1]. The lactate apparent clearance (Cl.F-1) was calculated from the area under the lactate concentration-time curve. The Cl.F-1 increased 1.81 (SEM 0.17) fold from PR to moderate AR (60 W) and only 1.31 (SEM 0.14) from PR to the most intense AR (180 W). Using the model, the apparent lactate production (F"K0) was also calculated. The F"K0 increased regularly following a slightly curvilinear function of VO2 and was 2.61 (SEM 0.53) fold greater during the most intense AR (180 W) than during PR. Because of the lack of data concerning the size of apparent lactate distribution volume (Vd), the apparent turnover rate (Rbl) has been presented here related to Vd. The Rbl.Vd-1 increased also following a slightly curvilinear function of VO2. The Rbl.Vd-1 was 85.90 (SEM 14.42) mumol.min-1.l-1 during PR and reached 314.09 (SEM 153.95) mumol.min-1.l-1 during the most intense AR (180 W). In conclusion the model presented here does not require labelled molecules and firstly makes it possible to follow the proportional change of apparent lactate clearance and apparent lactate production during active postexercise recovery in comparison with passive recovery conditions and secondly to estimate the blood lactate turnover.
Abstract: The purpose of this study is to present a mathematical model based on physiological observations which describes the evolution of the blood lactate concentration ([LA-]) versus the oxygen uptake (VO2) during a continuous graded exercise test. This model is based on several assumptions: 1) [LA-] reflects the balance between the rates of appearance and disappearance of the lactate in the blood compartment; 2) VO2 measured at the end of each step, is a linear function of the power output and thus of the time; 3) the appearance rate of lactate into the blood is an exponential function of VO2; 4) the rate of disappearance is a saturable process which can be modelized by Michaelis-Menten kinetics; 5) the volume of distribution of lactate in the blood compartment is a constant during exercise. The parameters used in this model correspond to the integration of several biochemical and physiological phenomenons. The originality of this approach is to express the rate of lactate appearance and disappearance versus VO2 rather than time. Whatever the general pattern of the data, the fitted curve gives always very good results. Especially, the theoretical curve fits the decrease in [LA-] usually observed during the first steps of such an exercise. From the computed parameters the evolution of lactate clearance during a continuous graded exercise test may be modelized. A strong relationship exists between the level of endurance training and the maximum lactate clearance (Clmax) reached during the exercise test. The VO2 for Clmax is an indicator of the shift of the relationship [LA-]-VO2. Then, we propose to use the maximum lactate clearance which is individually determined, to characterize the endurance level of an athlete.
Abstract: The purpose of this study is to present a simple kinetic model for the study of the lactate metabolism. This model based on pharmacokinetic theory, does not require labelled molecules and yields a finer approach to lactate metabolism than does a simple observation of blood lactate concentration. The variations in parameter values have been studied in six male subjects after intensive exercise (385 W, 110 rpm and 1 min) (IE) followed by three different recovery periods: passive recovery (RE), moderate exercise (ME) and heavy exercise (HE). Blood lactate concentration was measured prior to IE and during the first hour of recovery. After mathematical treatment, the results show that the apparent clearance increases 2.83 +/- 0.76 fold from RE to ME and 1.96 +/- 0.61 fold from RE to HE. The steady state blood lactate concentration induced by the intensity of recovery (La(ss)) increases slightly (1.53 +/- 0.37 fold) from RE (1.40 +/- 0.36 mmol.l-1) to ME (2.04 +/- 0.32 mmol.l-1). Then La(ss) increases markedly (3.78 +/- 0.91 mmol.l-1) during HE (2.81 +/- 0.78 fold the La(ss) value at RE). The ratio between the apparent rates of lactate production (F"K0) during RE, ME and HE was calculated. F"K0 increases in a linear way versus intensity of exercise recovery. It was concluded that in the human: 1) the blood lactate concentration is not an accurate indicator of lactate production, 2) in our experiment, the apparent lactate production is a linear function of exercise intensity and 3) the abruptly increasing blood lactate concentration at a high level of exercise intensity is due to a decrease in apparent clearance.
