Muscle Glycogen Sparing Research Articles

Impact of MCT Oil and Caffeine on Substrate Metabolism during Submaximal Exercise

Introduction: Recent research has suggested that medium-chain triglyceride (MCT) supplementation may increase fat oxidation (FatOx) during aerobic exercise, sparing muscle glycogen and, perhaps, enhancing performance. As both MCT and caffeine (CAF) are theorized to elicit these effects, this pilot study’s purpose was to compare the physiological responses of their combined supplementation during submaximal cycling exercise. Methods: Eight aerobically trained males (mean±SD; age 23.6±4.4 years; body mass 82.3±15.8 kg; height 180.9±8.7 cm) completed one aerobic capacity (VO2peak) test and three 45-min exercise trials at 60% VO2peak. Blinded and counterbalanced, one-hour prior to each trial, participants consumed: MCT+CAF (20 mL + 100 mg), long-chain triglycerides (LCT)+CAF (40 mL + 100 mg), or CAF (100 mg). Oxygen consumption (VO2), carbon dioxide output (VCO2), and minute ventilation (VE) were measured, subsequently calculating respiratory exchange ratio (RER), energy expenditure (EE), carbohydrate oxidation (CarbOx), and FatOx. Results: No significant differences between conditions were observed for average VO2 (p=0.474; η2=0.101), VE (p=0.323; η2=0.149), (RER (p=0.323; η2=0.149), EE (p=0.474; η2=0.101), CarbOx (p=0.274; η2=0.169), or FatOx (p=0.478; η2=0.100) or for total EE (p=0.474; η2=0.101), CarbOx (p=0.274; η2=0.169), or FatOx (p=0.478; η2=0.100). Conclusions: Co-ingestion of MCT+CAF didn’t produce any significantly different physiological responses compared to co-ingestion of LCT+CAF or the CAF control.

Activation of the erythropoietin system in exhaustively exercise muscle relates to ACE gene polymorphism-modulated metabolic signalling and mitochondrial transcript expression

Introduction
 Introduction A fall in muscle oxygen saturation is a potent activator of mitochondrial biogenesis in exercised skeletal muscle which is subject to the training-modulated influence of the insertion/deletion polymorphism of the angiotensin converting enzyme gene (ACE-I/D; Gasser et al 2022) and may involve paracrine erythropoietin (EPO) signaling (Desplanches et al 2014, Nijholt et al 2021). We tested the hypothesis that erythropoietin expression and signaling in fatiguingly exercised muscle would correspond to the expression of hypoxia-regulated mitochondrial genes and altered metabolic signaling and would be subject to a genetic influence by ACE-I/D.
 Methods
 Methods 22 healthy, male white Caucasian men (27.0 +/- 1.4 years; BMI 23.6 +/- 0.6 kg m-2) completed a session of fatiguing one-legged exercise in the fasted state. Microbiopsies were collected from m. vastus lateralis of the non-exercised leg immediately before exercise, and ½, 3, and 8 hours thereafter from the exercising leg. Levels of the hypoxia-regulated cytochrome c oxidase subunit 4 isoforms 1 and 2 (COX4I1 and COX4I2), ACE and EPO transcript, glycogen concentration in m. vastus lateralis, the ACE-I/D genotype and aerobic fitness state were assessed as described (Desplanches et al 2014; Gasser et al 2022). EPO protein concentration and phosphorylation of intracellular transducers of EPO signaling were quantified in muscle homogenates with validated enzyme-linked immune sorbent and a phospho-kinase assays. Effects and Pearson correlations were assessed with analysis of variance and declared significant at p < 0.05.
 Results
 One-legged exercise produced metabolic fatigue as indicated by the voluntary cessation of exercise and a reduced glycogen concentration in m. vastus lateralis in all subjects ½ hour after exercise (-0.044 mg mg-1). Concomitantly, EPO protein levels were 4-fold lowered; and subsequently increased 3-8 hours after cessation of exercise alike EPO transcripts levels.
 Aerobically fit ACE I-allele carriers demonstrated a sparing of muscle glycogen, exaggerated EPO transcript response, and higher phosphorylation levels of EPO signal transducers [STAT5a-Y694 (+31%), STAT5b-Y699 (+40%)]. The phosphorylation level of the metabolic signal transducer AMPKa2-T172 correlated to EPO transcript levels 3 hours post exercise (r = 0.61). EPO protein levels correlated to ACE and COX4I2 transcript levels (r = -0.79; -0.54).
 Discussion
 The findings highlight that a paracrine loop of metabolically-regulated EPO signaling exists in exercised human skeletal muscle which variability is associated with the ACE-I/D gene polymorphism in fair correspondence with a mitochondrial marker of local hypoxia.
 References
 Desplanches, D., Amami, M., Mueller, M., Hoppeler, H., Kreis, R., & Flück, M. (2014). Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work. European Journal of Applied Physiology, 114, 405-417. https://doi.org/10.1007/s00421-013-2783-8
 Gasser, B., Franchi, M. V., Ruoss, S., Frei, A., Popp, W. L., Niederseer, D., Catuogno, S., Frey, W. O., & Flück, M. (2022). Accelerated muscle deoxygenation in aerobically fit subjects during exhaustive exercise is associated with the ACE insertion allele. Frontiers in Sports and Active Living, 4, Article 814975. https://doi.org/10.3389/fspor.2022.814975
 Nijholt, K. T., Meems, L. M. G., Ruifrok, W. P. T., Maass, A. H., Yurista, S. R., Pavez-Giani, M. G., Mahmoud, B., Wolters, A. H. G., van Veldhuisen, D. J., van Gilst, W. H., Silljé, H. H. W., de Boer, R. A., & Westenbrink, B. D. (2021). The erythropoietin receptor expressed in skeletal muscle is essential for mitochondrial biogenesis and physiological exercise. Pflügers Archiv - European Journal of Physiology, 473, 1301-1313. https://doi.org/10.1007/s00424-021-02577-4

High-fat ketogenic diets and ketone monoester supplements differentially affect substrate metabolism during aerobic exercise.

Chronically adhering to high-fat ketogenic diets or consuming ketone monoester supplements elicits ketosis. Resulting changes in substrate metabolism appear to be drastically different between ketogenic diets and ketone supplements. Consuming a ketogenic diet increases fatty acid oxidation with concomitant decreases in endogenous carbohydrate oxidation. Increased fat oxidation eventually results in an accumulation of circulating ketone bodies, which are metabolites of fatty acids that serve as an alternative source of fuel. Conversely, consuming ketone monoester supplements rapidly increases circulating ketone body concentrations that typically exceed those achieved by adhering to ketogenic diets. Rapid increases in ketone body concentrations with ketone monoester supplementation elicit a negative feedback inhibition that reduces fatty acid mobilization during aerobic exercise. Supplement-derived ketosis appears to have minimal impact on sparing of muscle glycogen or minimizing of carbohydrate oxidation during aerobic exercise. This review will discuss the substrate metabolic and associated aerobic performance responses to ketogenic diets and ketone supplements.

Sparing Muscle Glycogen in Rats with Brown Sugarcane Supplementation

ABSTRACT Background: Carbohydrates supplementation before exercise is known to delay fatigue in athletes, especially for endurance type of sports. Brown sugarcane (Saccharum officinarum) mostly contains sucrose. The breakdown of sucrose into glucose and fructose is used by the body as an energy-providing substrate, especially when exercising for a long duration – endurance. Consumption of brown sugarcane before exercise is expected to keep blood glucose in normal condition and preventing from muscle glycogen catabolism. Objectives: This research aimed to investigate the effect of carbohydrate supplementation with brown sugarcane and glucose on blood glucose and muscle glycogen levels. Methods: 36 male Sprague Dawley rats at 8 weeks old were involved in this study. There were 4 groups of intervention, brown sugarcane + swimming (BS), glucose + swimming (G), water + swimming (W), and brown sugarcane without swimming (S). The dose of intervention was 0,3 g sucrose/100 g body weight of rats. The supplementation was given 10 minutes before doing the swimming activity. A statistical test with SPSS software was used to analyze the results. One-way ANOVA and t-test were used to analyze before and after supplementation. Results: The results showed that the rats who were given sugar cane supplementation before swimming had a smaller increase in blood glucose than the other groups. The increasing of blood glucose in each group were BS = 7.95 mg/dl; G = 21.19 mg/dl; W = 35.64 mg/dl; S = 4.57 mg/dl; p=0.000. Muscle glycogen levels in the rats given sugar cane supplementation group were higher than in the other groups (p=0.000). Conclusions: Carbohydrate supplementation with brown sugarcane before endurance type of exercise was able to maintain blood glucose on normal condition and prevent muscle glycogen catabolism in experimental animals. Research on the development of sports spesific products based on brown sugarcane can be carried out to see its effects directly on humans. Keywords: brown sugarcane, glucose, glicogen, swimming, carbohydrates

The Influence Of A Whey Protein Preload Prior To Carbohydrate Consumption On Cycling Performance

INTRODUCTION: The consumption of carbohydrates during a bout of endurance exercise has been shown to promote a glycogen sparing effect and lead to an improvement in exercise performance. The consumption of whey protein prior to a prolonged bout of endurance exercise may augment insulin secretion and further spare muscle glycogen. PURPOSE: To examine if a whey protein solution consumed as a preload prior to a glucose bolus influenced performance and metabolic responses during a cycling performance trial. METHODS: Ten recreationally trained cyclists and triathletes completed two experimental trials. Each participant was required to perform two separate cycling performance tests, which consisted of cycling for 30 min at 90% lactate threshold, followed by a 30 min time trial. Participants consumed a whey protein isolate preload (0.7 g/kg/LBM) or a placebo 20 min prior to the consumption of a glucose beverage (0.9 g/kg/LBM). The glucose beverage was consumed 10 min prior to the cycling performance test. During both trials, plasma glucose, c-peptide, insulin, glucagon, and NEFA concentrations were measured. RESULTS: There were no significant differences in overall time trial performance (WP 16.8 ± 0.34 km; PL 17 ± 0.4 km; p = .346). WP stimulated a significant increase in plasma insulin concentrations at time point 0 (WP = 222.88 ± 45.1 pg/ml; PL = 85.95 ± 45.1 pg/ml; p = .047) compared to the placebo trial. Despite an increase in plasma insulin, there were no significant timepoint differences for plasma glucose. WP stimulated a significant increase in plasma glucagon concentrations for timepoint -10, 0, 15, 30, 45, and 60 when compared to the PL trial (all values p < .05). CONCLUSION: Although there were significant alterations in plasma insulin concentration due to the consumption of the whey protein isolate preload, this did not influence overall cycling performance or substrate utilization. Funding Source: National Strength and Conditioning Association – GNC Sport Nutrition Grant

Exogenous ketosis impacts neither performance nor muscle glycogen breakdown in prolonged endurance exercise.

Available evidence indicates that ketone bodies inhibit glycolysis in contracting muscles. Therefore, we investigated whether acute exogenous ketosis by oral ketone ester (KE) intake early in a simulated cycling race can induce transient glycogen sparing by glycolytic inhibition, thereby increasing glycogen availability in the final phase of the event. In a randomized crossover design, 12 highly trained male cyclists completed a simulated cycling race (RACE), which consisted of 3-h intermittent cycling (IMT180′), a 15-min time trial (TT15′), and a maximal sprint (SPRINT). During RACE, subjects received 60 g carbohydrates/h combined with three boluses (25, 20, and 20 g) (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) or a control drink (CON) at 60 and 20 min before and at 30 min during RACE. KE intake transiently increased blood d-β-hydroxybutyrate to ~3 mM (range: 2.6–5.2 mM) during the first half of RACE (P < 0.001 vs. CON). Blood pH concomitantly decreased from approximately 7.42 to 7.36 (range: 7.29–7.40), whereas bicarbonate dropped from 26.0 to 21.6 mM (range: 20.1–23.7; both P < 0.001 vs. CON). Net muscle glycogen breakdown during IMT180′ [KE: −78 ± 30 (SD); CON: −60 ± 22 mmol/kg wet wt; P = 0.08] and TT15′ (KE: −9 ± 18; CON: −18 ± 18 mmol/kg wet wt; P = 0.35) was similar between KE and CON. Accordingly, mean power output during TT15′ (KE: 273 ± 38; CON: 272 ± 37 W; P = 0.83) and time-to-exhaustion in the SPRINT (KE: 59 ± 16; CON: 58 ± 17 s; P = 0.66) were similar between conditions. In conclusion, KE intake during a simulated cycling race does not cause glycogen sparing, nor does it affect all-out performance in the final stage of a simulated race.NEW & NOTEWORTHY Exogenous ketosis produced by oral ketone ester ingestion during the early phase of prolonged endurance exercise and against the background of adequate carbohydrate intake neither causes muscle glycogen sparing nor improves performance in the final stage of the event. However, such exogenous ketosis may decrease buffering capacity in the approach of the final episode of the event. Furthermore, ketone ester intake during exercise may reduce appetite immediately after exercise.

Probiotic supplementation increases carbohydrate metabolism in trained male cyclists: a randomized, double-blind, placebo-controlled crossover trial.

We hypothesized that probiotic supplementation (PRO) increases the absorption and oxidation of orally ingested maltodextrin during 2 h endurance cycling, thereby sparing muscle glycogen for a subsequent time trial (simulating a road race). Measurements were made of lipid and carbohydrate oxidation, plasma metabolites and insulin, gastrointestinal (GI) permeability, and subjective symptoms of discomfort. Seven male cyclists were randomized to PRO (bacterial composition given in methods) or placebo for 4 wk, separated by a 14-day washout period. After each period, cyclists consumed a 10% maltodextrin solution (initial 8 mL/kg bolus and 2 mL/kg every 15 min) while exercising for 2 h at 55% maximal aerobic power output, followed by a 100-kJ time trial. PRO resulted in small increases in peak oxidation rates of the ingested maltodextrin (0.84 ± 0.10 vs. 0.77 ± 0.09 g/min; P = 0.016) and mean total carbohydrate oxidation (2.20 ± 0.25 vs. 1.87 ± 0.39 g/min; P = 0.038), whereas fat oxidation was reduced (0.40 ± 0.11 vs. 0.55 ± 0.10 g/min; P = 0.021). During PRO, small but significant increases were seen in glucose absorption, plasma glucose, and insulin concentration and decreases in nonesterified fatty acid and glycerol. Differences between markers of GI damage and permeability and time-trial performance were not significant (P > 0.05). In contrast to the hypothesis, PRO led to minimal increases in absorption and oxidation of the ingested maltodextrin and small reductions in fat oxidation, whereas having no effect on subsequent time-trial performance.

Fueling and Recovery

As ultra-endurance races continue to rise in popularity, it is critical that athletes understand how to nourish their bodies with proper amounts of calories from carbohydrate, protein, and fat. The importance of carbohydrate for fueling endurance exercise and protein for recovery is well established; however, the role of fat is debated. Specific amounts of carbohydrate per kilogram of body weight are recommended for before, during, and after ultra-endurance exercise. Total grams of protein per day and after exercise are established. After carbohydrate and protein needs are determined the balance of calories typically come from fat. Using fat for energy during endurance exercise is not a new concept, but continues to be studied as way of fueling while sparing muscle glycogen.

Muscle Glycogen Utilization During an Australian Rules Football Game.

To better understand the carbohydrate (CHO) requirement of Australian Football (AF) match play by quantifying muscle glycogen utilization during an in-season AF match. After a 24-h CHO-loading protocol of 8 and 2g/kg in the prematch meal, 2 elite male forward players had biopsies sampled from m. vastus lateralis before and after participation in a South Australian Football League game. Player A (87.2kg) consumed water only during match play, whereas player B (87.6kg) consumed 88g CHO via CHO gels. External load was quantified using global positioning system technology. Player A completed more minutes on the ground (115 vs 98min) and covered greater total distance (12.2 vs 11.2km) than player B, although with similar high-speed running (837 vs 1070m) and sprinting (135 vs 138m). Muscle glycogen decreased by 66% in player A (pre: 656mmol/kg dry weight [dw], post: 223mmol/kg dw) and 24% in player B (pre: 544mmol/kg dw, post: 416mmol/kg dw). Prematch CHO loading elevated muscle glycogen concentrations (ie,>500mmol/kg dw), the magnitude of which appears sufficient to meet the metabolic demands of elite AF match play. The glycogen cost of AF match play may be greater than in soccer and rugby, and CHO feeding may also spare muscle glycogen use. Further studies using larger sample sizes are now required to quantify the interindividual variability of glycogen cost of match play (including muscle and fiber-type-specific responses), as well examining potential metabolic and ergogenic effects of CHO feeding.

HUBUNGAN ASUPAN KARBOHIDRAT DAN STATUS GIZI DENGAN TINGKAT KEBUGARAN JASMANI PADA ATLET BASKET REMAJA SISWA SEKOLAH MENENGAH PERTAMA

Good physical fi tness in athletes is essential in order to reach maximum performance during the game. Factors which affect the physical fi tness are nutrition intake, nutritional status dan age. The role of carbohydrates in sports is very important to spare muscle glycogen during exercise. This study purpose was to analyze the correlation between carbohydrate intake, nutritional status and physical fi tness in adolescent athletes of junior high school. This study used a cross-sectional study design. Total subjects in this study using a total population of about 37 people who are members of basketball team in junior high school 2 Ngamprah West Bandung District. Data of Carbohydrate intake was obtained through semi quantitative food frequency questionnaire method. Nutritional status was obtained by measuring body weight using digital bathroom scales and measuring height using microtoise tools. The average intake of carbohydrates was 375.4 grams which was 29.7% have a less carbohydrate intake and 70.3% have a adequate carbohydrate intake, average BMI for age z-score was -0.166 SD as much as 2.7% have a very thin nutritional status, 5.4% have a thin nutritional status, 70.3% have a normal nutritional status, 13.5% overweight and 8.1% obese. The average fi tness score was 14.9 (range 5-20) that means average they have a good physical fi tness which was as much as 13.5% have a lack physical fi tness and 86.5% have a good physical fi tness. Results revealed that there is correlation between carbohydrate intake and physical fi tness (p=0.025 and r= -0.367), nutritional status and physical fi tness (p =0.038 and r = 0.342). The conclusion of this study is carbohydrate intake and nutritional status related to the physical fi tness of adolescence basketballs athletes. Adolescent basketball athletes are advised to provide carbohydrate intake and maintain their nutritional status in the normal category in order to have good physical fi tness.

Pre-exercise nutrition: the role of macronutrients, modified starches and supplements on metabolism and endurance performance.

Endurance athletes rarely compete in the fasted state, as this may compromise fuel stores. Thus, the timing and composition of the pre-exercise meal is a significant consideration for optimizing metabolism and subsequent endurance performance. Carbohydrate feedings prior to endurance exercise are common and have generally been shown to enhance performance, despite increasing insulin levels and reducing fat oxidation. These metabolic effects may be attenuated by consuming low glycemic index carbohydrates and/or modified starches before exercise. High fat meals seem to have beneficial metabolic effects (e.g., increasing fat oxidation and possibly sparing muscle glycogen). However, these effects do not necessarily translate into enhanced performance. Relatively little research has examined the effects of a pre-exercise high protein meal on subsequent performance, but there is some evidence to suggest enhanced pre-exercise glycogen synthesis and benefits to metabolism during exercise. Finally, various supplements (i.e., caffeine and beetroot juice) also warrant possible inclusion into pre-race nutrition for endurance athletes. Ultimately, further research is needed to optimize pre-exercise nutritional strategies for endurance performance.

Effects of Protein in Combination with Carbohydrate Supplements on Acute or Repeat Endurance Exercise Performance: A Systematic Review

Protein supplements are consumed frequently by athletes and recreationally active adults for various reasons, including improved exercise performance and recovery after exercise. Yet, far too often, the decision to purchase and consume protein supplements is based on marketing claims rather than available evidence-based research. The purpose of this review was to provide a systematic and comprehensive analysis of the literature that tested the hypothesis that protein supplements, when combined with carbohydrate, directly enhance endurance performance by sparing muscle glycogen during exercise and increasing the rate of glycogen restoration during recovery. The analysis was used to create evidence statements based on an accepted strength of recommendation taxonomy. English language articles were searched with PubMed and Google Scholar using protein and supplements together with performance, exercise, competition, and muscle, alone or in combination as keywords. Additional articles were retrieved from reference lists found in these papers. Inclusion criteria specified recruiting healthy active adults less than 50 years of age and evaluating the effects of protein supplements in combination with carbohydrate on endurance performance metrics such as time-to-exhaustion, time-trial, or total power output during sprint intervals. The literature search identified 28 articles, of which 26 incorporated test metrics that permitted exclusive categorization into one of the following sections: ingestion during an acute bout of exercise (n = 11) and ingestion during and after exercise to affect subsequent endurance performance (n = 15). The remaining two articles contained performance metrics that spanned both categories. All papers were read in detail and searched for experimental design confounders such as energy content of the supplements, dietary control, use of trained or untrained participants, number of subjects recruited, direct measures of muscle glycogen utilization and restoration, and the sensitivity of the test metrics to explain the discrepant findings. Our evidence statements assert that when carbohydrate supplementation was delivered at optimal rates during or after exercise, protein supplements provided no further ergogenic effect, regardless of the performance metric used. In addition, the limited data available suggested recovery of muscle glycogen stores together with subsequent rate of utilization during exercise is not related to the potential ergogenic effect of protein supplements. Many studies lacked ability to measure direct effects of protein supplementation on muscle metabolism through determination of muscle glycogen, kinetic assessments of protein turnover, or changes in key signaling proteins, and therefore could not substantiate changes in rates of synthesis or degradation of protein. As a result, the interpretation of their data was often biased and inconclusive since they lacked ability to test the proposed underlying mechanism of action. When carbohydrate is delivered at optimal rates during or after endurance exercise, protein supplements appear to have no direct endurance performance enhancing effect.

Distinct effects of leucine or a mixture of the branched-chain amino acids (leucine, isoleucine, and valine) supplementation on resistance to fatigue, and muscle and liver-glycogen degradation, in trained rats

ObjectiveThe aim of this study was to evaluate the effects of the mixture of branched-chain amino acids (BCAAs) supplementation compared with leucine administered orally on muscle biochemical parameters of trained rats submitted to an exercise-induced protocol of glycogen depletion. MethodsAfter 6 wk of swimming exercise, 8 wk-old (250 g, adult) male Wistar rats were randomly divided into three experimental groups (n = 8 per group): the mixture of BCAAs (BCAAs), leucine (LEU), and placebo (PLA). All groups were submitted to swimming exercise for 6 wk and supplemented with either the mixture of BCAAs, leucine, or placebo during the last week of training. At week 7 of the protocol, the rats were submitted to an intermittent, progressive swimming test until exhaustion and sacrificed. Muscle gastrocnemius and liver were depicted to determine total glycogen, tricarboxylic acid cycle (TCA) intermediates, and enzymatic activities. Statistical evaluation was performed by one-way analysis of variance with Tukey post hoc test. ResultsBoth muscle and liver glycogen degradation ratio were significantly higher in the mixture of BCAAs group compared to the PLA group (P < 0.05) and the LEU group presented decreased liver glycogen degradation ratio compared with the mixture of BCAAs group (P < 0.05). Both muscle and liver glycogen content were significantly spared in the mixture of BCAAs and LEU groups compared to the PLA group (P < 0.01). A performance test demonstrated that LEU supplementation enhanced resistance to exhaustion compared to the mixture of BCAAs (P < 0.001), however, no difference was found when LEU supplementation was compared to PLA (P > 0.05) Muscle citrate content was significantly higher in the mixture of BCAAs group compared with the PLA group (P < 0.001). Muscle malate content was significantly elevated in the mixture of BCAAs group compared with both the PLA (P < 0.001) and LEU groups (P < 0.001). BCAT activity was significantly reduced in the mixture of BCAAs supplementation group compared with the LEU group (P < 0.001). ConclusionLeucine supplementation improved performance compared with the mixture of BCAAs supplementation, sparing muscle glycogen stores despite the augmentation of some TCA intermediate concentrations on the left side of the TCA cycle.

Effects of ASEA beverage intake on endurance performance in mice

Previous research with ASEA (a saline beverage with stable superoxide complexes) found increased fatty acid mobilization in cyclists after 7 d ingestion. We hypothesized that run time to exhaustion would be favorably influenced by ASEA intake due to enhanced fatty acid oxidation and muscle glycogen sparing. Sixty mice were randomized to 1 of 4 treatment groups (n=15 each): placebo sedentary (PS), ASEA sedentary (AS), placebo run (PR), and ASEA run (AR). Mice were gavaged daily with ASEA or placebo (0.3 ml/d) for 7 d. PR and AR groups were run to exhaustion (24 m/min) at the end of the 7‐d gavage period, with AR running significantly longer than PR (68.0±9.2 vs. 52.8±7.4 min, respectively) (p&lt;0.001). At the point of exhaustion, liver glycogen was undetectable for both AR and PR. When adjusted to run time, the estimated rate of muscle glycogen depletion was different between AR and PR (0.036±0.014 and 0.052±0.018 ug/mg protein per min, respectively, p=0.017). Skeletal muscle phosphorylated acetyl‐CoA carboxylase (p‐ACC) was significantly increased in AR compared to AS (p=0.020) and PR (p=0.045). Fatty acyl CoA transport (CPT1), and beta‐oxidation (beta‐HAD) were not different between AR and PR. ASEA increased run time to exhaustion by 29% in mice, potentially through less inhibition of fatty acid oxidation via increased P‐ACC, and muscle glycogen sparing percent (30%).Funded by Reoxcyn Discoveries Group.

ACTN 3 e desempenho esportivo: um gene candidato ao sucesso em provas de curta e longa duração.&lt;br&gt;DOI:10.5007/1980-0037.2011v13n6p477

The aim of the present study was to review the evidence on the relationship between the R577X polymorphism of the ACTN3 gene and sports performance. The Pubmed database was searched using ACTN3 gene AND sports performance as keywords. The ACTN3 gene encodes a muscle-specific protein, called α-actinin-3, which is only present in type II fibers. Most studies have demonstrated a relationship between the presence of α-actinin-3 and the ability of muscle to generate force. However, recent studies suggest that the absence of the functional form of this protein may regulate substrate utilization during exercise, giving priority to oxidative metabolism, sparing muscle glycogen, and improving performance in long-duration events. Nevertheless, further studies involving humans are needed to better understand the metabolic role of this protein.

Carbohydrate Ingestion during Team Games Exercise

There is a growing body of research on the influence of ingesting carbohydrate-electrolyte solutions immediately prior to and during prolonged intermittent, high-intensity exercise (team games exercise) designed to replicate field-based team games. This review presents the current body of knowledge in this area, and identifies avenues of further research. Almost all early work supported the ingestion of carbohydrate-electrolyte solutions during prolonged intermittent exercise, but was subject to methodological limitations. A key concern was the use of exercise protocols characterized by prolonged periods at the same exercise intensity, the lack of maximal- or high-intensity work components and long periods of seated recovery, which failed to replicate the activity pattern or physiological demand of team games exercise. The advent of protocols specifically designed to replicate the demands of field-based team games enabled a more externally valid assessment of the influence of carbohydrate ingestion during this form of exercise. Once again, the research overwhelmingly supports carbohydrate ingestion immediately prior to and during team games exercise for improving time to exhaustion during intermittent running. While the external validity of exhaustive exercise at fixed prescribed intensities as an assessment of exercise capacity during team games may appear questionable, these assessments should perhaps not be viewed as exhaustive exercise tests per se, but as indicators of the ability to maintain high-intensity exercise, which is a recognized marker of performance and fatigue during field-based team games. Possible mechanisms of exercise capacity enhancement include sparing of muscle glycogen, glycogen resynthesis during low-intensity exercise periods and attenuated effort perception during exercise. Most research fails to show improvements in sprint performance during team games exercise with carbohydrate ingestion, perhaps due to the lack of influence of carbohydrate on sprint performance when endogenous muscle glycogen concentration remains above a critical threshold of ∼200 mmol/kg dry weight. Despite the increasing number of publications in this area, few studies have attempted to drive the research base forward by investigating potential modulators of carbohydrate efficacy during team games exercise, preventing the formulation of optimal carbohydrate intake guidelines. Potential modulators may be different from those during prolonged steady-state exercise due to the constantly changing exercise intensity and frequency, duration and intensity of rest intervals, potential for team games exercise to slow the rate of gastric emptying and the restricted access to carbohydrate-electrolyte solutions during many team games. This review highlights fluid volume, carbohydrate concentration, carbohydrate composition and solution osmolality; the glycaemic index of pre-exercise meals; fluid and carbohydrate ingestion patterns; fluid temperature; carbohydrate mouthwashes; carbohydrate supplementation in different ambient temperatures; and investigation of all of these areas in different subject populations as important avenues for future research to enable a more comprehensive understanding of carbohydrate ingestion during team games exercise.

Boosting fat burning with carnitine: an old friend comes out from the shadow

Understanding the regulation of fuel utilization has been a topic of great interest and has practical implications to athletic performance and to prevention of pathophysiological metabolic conditions. The balance between carbohydrates (CHO) and lipids is regulated by a complex system with multi-site feedback and feedforward control as well as interaction between the pathways. Carnitine has a crucial role in lipid oxidation by mediating the translocation of long-chained fatty acids into mitochondria. During the past 30 years, dietary supplementation with carnitine has been widely used in order to enhance lipid oxidation and increase exercise performance. The evidence for an ergogenic effect of carnitine is, however, limited and most studies show no effect of carnitine supplementation on lipid oxidation. This is hardly unexpected since there is hitherto no evidence that muscle carnitine content can be increased by carnitine feeding in healthy men. In a recent issue of The Journal of Physiology, Wall and colleagues were able to show for the first time that muscle carnitine can be increased in healthy men by dietary carnitine supplementation (Wall et al. 2011). The same research group led by Paul Greenhaff has shown in a previous study that 6 h intravenous infusion with a combination of carnitine and insulin elevated muscle carnitine by 13% (Stephens et al. 2006). The mechanism is probably related to stimulation by insulin of the Na+-coupled transmembrane carnitine transport and is the theoretical foundation for the present study, where carnitine feeding was combined with CHO. Three months of dietary supplementation with a combination of carnitine and CHO had no effect, but after 6 months muscle carnitine content increased by 21%. The necessity of using a very long supplementation period demonstrates the difficulties involved and explains the failure of previous studies with shorter intervention periods. In this work, they have not only shown increased muscle carnitine but also that this alters muscle metabolism during exercise. Firstly, during low-intensity exercise (50%) carnitine supplementation resulted in reduced glycogen utilization and reduced activity of the pyruvate dehydrogenase complex (PDC). PDC is a main control point of CHO oxidation and has a complex mode of control including feedback inhibition by the products acetyl-CoA and NADH (Fig. 1). The investigators suggest that the reduced PDC activity is due to a carnitine-mediated increase in lipid-derived acetyl-CoA. Although this explanation is consistent with theoretical models (Randle et al. 1963) the current data give limited experimental support in that the acetyl-carnitine/carnitine ratio, which reflects the acetyl-CoA/CoA ratio, was lower after carnitine supplementation. The carnitine-induced sparing of muscle glycogen is an important finding and is consistent with an increased lipid oxidation. However, an obvious limitation of this study is that there are no measurements of lipid oxidation, which should have been one of the primary outcomes. Another finding in this work, was that at high-intensity exercise (80%) muscle lactate was reduced after carnitine supplementation. Simultaneously PDC activity was increased, i.e. opposite to that observed during low-intensity exercise. The increased PDC activity was explained by the role of carnitine in buffering acetyl-groups giving rise to reduced levels of the PDC inhibitor acetyl-CoA. The lower muscle lactate after carnitine supplementation suggests a better matching between glycolytic flux and CHO oxidation. Carnitine supplementation also had an ergogenic effect and was shown to increase work output by 11% in a performance trial with a fixed duration of 30 min. The ergogenic effect was explained by the dual role of carnitine – glycogen sparing at low intensities and reduced muscle lactate accumulation at high intensities. This well controlled study by Wall et al. 2011, has broad implications. An important and robust finding is that muscle carnitine can be increased by dietary means in subjects without carnitine deficiencies and that this has a clear influence on muscle metabolism and performance. The results may have significant implications for athletic performance but the requirements of long-term treatment will most likely restrict the use of carnitine as an ergogenic aid. The results may also have some clinical importance in the treatment of type 2 diabetes and other metabolic diseases, which are related to a deteriorated lipid metabolism. It may be anticipated that further work on this subject will determine whether carnitine can specifically enhance lipid oxidation.

Chronic oral ingestion of l‐carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans

We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50% , 30 min at 80% , then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50% , the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80% , muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an improvement in exercise performance.

LXR activation prevents exhaustive exercise-induced hypoglycaemia and spares muscle glycogen but does not enhance running endurance in untrained rats

Liver X receptors (LXRs) are ligand-activated transcription factors that play an important role in regulation of hepatic lipid and carbohydrate metabolism. However, to date there is very few information on the role of LXRs in skeletal muscle. Moreover, it remains obscure whether LXR activation affects physical endurance. Therefore, we aimed to examine effects of selective LXR activator--T0901317--on running endurance and skeletal muscle exercise metabolism in rats. The animals were assigned to two groups (n=20) receiving either vehicle or T0901317 (10 mg kg(-1) day(-1) ) for 1 week. One day after the final administration, half of the rats in each group were exercised until exhaustion on the electrically driven treadmill. All animals were then anaesthetized and samples of the soleus, red and white sections of the gastrocnemius muscle, epididymal fat pad and liver were excised. We found that LXR activation prevented exhaustive exercise-induced hypoglycaemia. T0901317 also shifted substrate utilization in working muscles in favour of fatty acids as indicated by its glycogen sparing effect, enhanced consumption of intramuscular triacylglycerol and upregulation of genes promoting fatty acid oxidation and suppressing carbohydrate oxidation. However, running time to exhaustion was not improved. We conclude that LXR activation increases fatty acid utilization during exercise which, however, does not translate into measurable enhancement of exercise endurance.

Carbohydrate Administration and Exercise Performance

It is well established that carbohydrate (CHO) administration increases performance during prolonged exercise in humans and animals. The mechanism(s), which could mediate the improvement in exercise performance associated with CHO administration, however, remain(s) unclear. This review focuses on possible underlying mechanisms that could explain the increase in exercise performance observed with the administration of CHO during prolonged muscle contractions in humans and animals. The beneficial effect of CHO ingestion on performance during prolonged exercise could be due to several factors including (i) an attenuation in central fatigue; (ii) a better maintenance of CHO oxidation rates; (iii) muscle glycogen sparing; (iv) changes in muscle metabolite levels; (v) reduced exercise-induced strain; and (vi) a better maintenance of excitation-contraction coupling. In general, the literature indicates that CHO ingestion during exercise does not reduce the utilization of muscle glycogen. In addition, data from a meta-analysis suggest that a dose-dependent relationship was not shown between CHO ingestion during exercise and an increase in performance. This could support the idea that providing enough CHO to maintain CHO oxidation during exercise may not always be associated with an increase in performance. Emerging evidence from the literature shows that increasing neural drive and attenuating central fatigue may play an important role in increasing performance during exercise with CHO supplementation. In addition, CHO administration during exercise appears to provide protection from disrupted cell homeostasis/integrity, which could translate into better muscle function and an increase in performance. Finally, it appears that during prolonged exercise when the ability of metabolism to match energy demand is exceeded, adjustments seem to be made in the activity of the Na+/K+ pump. Therefore, muscle fatigue could be acting as a protective mechanism during prolonged contractions. This could be alleviated when CHO is administered resulting in the better maintenance of the electrical properties of the muscle fibre membrane. The mechanism(s) by which CHO administration increases performance during prolonged exercise is(are) complex, likely involving multiple factors acting at numerous cellular sites. In addition, due to the large variation in types of exercise, durations, intensities, feeding schedules and CHO types it is difficult to assess if the mechanism(s) that could explain the increase in performance with CHO administration during exercise is(are) similar in different situations. Experiments concerning the identification of potential mechanism(s) by which performance is increased with CHO administration during exercise will add to our understanding of the mechanism(s) of muscle/central fatigue. This knowledge could have significant implications for improving exercise performance.