Protein dose requirements to maximize skeletal muscle protein synthesis after repeated bouts of resistance exercise in young trained women.

Studies examining the effect of protein (PRO) feeding on post resistance exercise (RE) muscle protein synthesis (MPS) have primarily been performed in men, and little evidence is available regarding the quantity of PRO required to maximally stimulate MPS in trained women following repeated bouts of RE. We therefore quantified acute (4 h and 8 h) and extended (24 h) effects of two bouts of resistance exercise, alongside protein-feeding, in women, and the PRO requirement to maximize MPS. Twenty-four RE trained women (26.6 ± 0.7 years, mean ± SEM) performed two bouts of whole-body RE (3 × 8 repetitions/maneuver at 75% 1-repetition maximum) 4 h apart, with post-exercise ingestion of 15 g, 30 g, or 60 g whey PRO (n = 8/group). Saliva, venous blood, and a vastus lateralis muscle biopsy were taken at 0 h, 4 h, 8 h, and 24 h post-exercise. Plasma leucine and branched chain amino acids were quantified using gas chromatography mass spectrometry (GC-MS) after ingestion of D2 O. Fifteen grams PRO did not alter plasma leucine concentration or myofibrillar synthetic rate (MyoFSR). Thirty and sixty grams PRO increased plasma leucine concentration above baseline (105.5 ± 5.3 µM; 120.2 ± 7.4 µM, respectively) at 4 h (151.5 ± 8.2 µM, p < 0.01; 224.8 ± 16.0 µM, p < 0.001, respectively) and 8 h (176.0 ± 7.3 µM, p < 0.001; 281.7 ± 21.6 µM, p < 0.001, respectively). Ingestion of 30 g PRO increased MyoFSR above baseline (0.068 ± 0.005%/h) from 0 to 4 h (0.140 ± 0.021%/h, p < 0.05), 0 to 8 h (0.121 ± 0.012%/h, p < 0.001), and 0 to 24 h (0.099 ± 0.011%/h, p < 0.01). Ingestion of 60 g PRO increased MyoFSR above baseline (0.063 ± 0.003%/h) from 0 to 4 h (0.109 ± 0.011%/h, p < 0.01), 0 to 8 h (0.093 ± 0.008%/h, p < 0.01), and 0 to 24 h (0.086 ± 0.006%/h, p < 0.01). Post-exercise ingestion of 30 g or 60 g PRO, but not 15 g, acutely increased MyoFSR following two consecutive bouts of RE and extended the anabolic window over 24 h. There was no difference between the 30 g and 60 g responses.

Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men.

Higher plasma leucine, isoleucine and valine (BCAA) concentrations are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. Fasting plasma BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m2; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m2; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m2; 46 ± 8 y) then underwent 6-weeks of VLCD (600-800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, p < 0.001). Despite significant weight loss (baseline 103.9 ± 12.3 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m2), no changes were observed in BCAAs after 6-weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19 ± 0.62 to 0.51 ± 0.21 post-VLCD; p < 0.001), Pearson's r revealed no relationships between BCAA and HOMA-IR, either before (leucine R2: 2.49e-005, p = 0.98; isoleucine R2: 1.211-e006, p = 0.9; valine R2: 0.004, p = 0.85) or after VLCD (leucine R2: 0.003, p = 0.86; isoleucine R2: 0.006, p = 0.82; valine R2: 0.002, p = 0.65). Plasma BCAA are higher in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight.

Age-related changes in muscle architecture and metabolism in humans: The likely contribution of physical inactivity to age-related functional decline.

In the United Kingdom (UK), it is projected that by 2035 people aged >65 years will make up 23 % of the population, with those aged >85 years accounting for 5% of the total population. Ageing is associated with progressive changes in muscle metabolism and a decline in functional capacity, leading to a loss of independence. Muscle metabolic changes associated with ageing have been linked to alterations in muscle architecture and declines in muscle mass and insulin sensitivity. However, the biological features often attributed to muscle ageing are also seen in controlled studies of physical inactivity (e.g. reduced step-count and bed-rest), and it is currently unclear how many of these ageing features are due to ageing per se or sedentarism. This is particularly relevant at a time of home confinements reducing physical activity levels during the Covid-19 pandemic. Current knowledge gaps include the relative contribution that physical inactivity plays in the development of many of the negative features associated with muscle decline in older age. Similarly, data demonstrating positive effects of government recommended physical activity guidelines on muscle health are largely non-existent. It is imperative therefore that research examining interactions between ageing, physical activity and muscle mass and metabolic health is prioritised so that it can inform on the "normal" muscle ageing process and on strategies for improving health span and well-being. This review will focus on important changes in muscle architecture and metabolism that accompany ageing and highlight the likely contribution of physical inactivity to these changes.

Impacts of rat hindlimb Fndc5/irisin overexpression on muscle and adipose tissue metabolism.

Myokines, such as irisin, have been purported to exert physiological effects on skeletal muscle in an autocrine/paracrine fashion. In this study, we aimed to investigate the mechanistic role of in vivo fibronectin type III domain-containing 5 (Fndc5)/irisin upregulation in muscle. Overexpression (OE) of Fndc5 in rat hindlimb muscle was achieved by in vivo electrotransfer, i.e., bilateral injections of Fndc5 harboring vectors for OE rats (n = 8) and empty vector for control rats (n = 8). Seven days later, a bolus of D2O (7.2 mL/kg) was administered via oral gavage to quantify muscle protein synthesis. After an overnight fast, on day 9, 2-deoxy-d-glucose-6-phosphate (2-DG6P; 6 mg/kg) was provided during an intraperitoneal glucose tolerance test (2 g/kg) to assess glucose handling. Animals were euthanized, musculus tibialis cranialis muscles and subcutaneous fat (inguinal) were harvested, and metabolic and molecular effects were evaluated. Muscle Fndc5 mRNA increased with OE (~2-fold; P = 0.014), leading to increased circulating irisin (1.5 ± 0.9 to 3.5 ± 1.2 ng/mL; P = 0.049). OE had no effect on protein anabolism or mitochondrial biogenesis; however, muscle glycogen was increased, along with glycogen synthase 1 gene expression (P = 0.04 and 0.02, respectively). In addition to an increase in glycogen synthase activation in OE (P = 0.03), there was a tendency toward increased glucose transporter 4 protein (P = 0.09). However, glucose uptake (accumulation of 2-DG6P) was identical. Irisin elicited no endocrine effect on mitochondrial biogenesis or uncoupling proteins in white adipose tissue. Hindlimb overexpression led to physiological increases in Fndc5/irisin. However, our data indicate limited short-term impacts of irisin in relation to muscle anabolism, mitochondrial biogenesis, glucose uptake, or adipose remodeling.

Maximal-intensity exercise does not fully restore muscle pyruvate dehydrogenase complex activation after 3 days of high-fat dietary intake.

BACKGROUND & AIMS: Exercise activates muscle pyruvate dehydrogenase complex (PDC), but moderate intensity exercise fails to fully activate muscle PDC after high-fat diet [1]. We investigated whether maximal intensity exercise overcomes this inhibition. METHODS: Quadriceps femoris muscle biopsy samples were obtained from healthy males at rest, and after 46 and 92 electrically-evoked maximal intermittent isometric contractions, which were preceded by 3 days of either low- (18%) or high- (69%) isocaloric dietary fat intake (LFD and HFD, respectively). RESULTS: The ratio of PDCa (active form) to total PDCt (fully activated) at rest was 50% less after HFD (0.32 ± 0.01 vs 0.15 ± 0.01; P < 0.05). This ratio increased to 0.77 ± 0.06 after 46 contractions (P < 0.001) and to 0.98 ± 0.07 after 92 contractions (P < 0.001) in LFD. The corresponding values after HFD were less (0.54 ± 0.06; P < 0.01 and 0.70 ± 0.07; P < 0.01, respectively). Resting muscle acetyl-CoA and acetylcarnitine content was greater after HFD than LFD (both P < 0.05), but their rate of accumulation in the former was reduced during contraction. Muscle lactate content after 92 contractions was 30% greater after HFD (P < 0.05). Muscle force generation during contraction was no different between interventions, but HFD lengthened muscle relaxation time (P < 0.05). Daily urinary total carnitine excretion after HFD was 2.5-fold greater than after LFD (P < 0.01). CONCLUSIONS: A bout of maximal intense exercise did not overcome dietary fat-mediated inhibition of muscle pyruvate dehydrogenase complex activation, and was associated with greater muscle lactate accumulation, as a result of lower PDC flux, and increased muscle relaxation time.

Muscle thickness correlates to muscle cross-sectional area in the assessment of strength training-induced hypertrophy.

Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Nine healthy, young, male volunteers (24 ± 2 y.o., BMI 24.1 ± 2.8 kg/m2 ) had vastus lateralis (VL) muscle volume (VOL) and ACSAmid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student's paired t test. The relationships between MRI and ultrasound measurements were tested by Pearson's correlation. After RT, MT increased by 7.5 ± 6.1% (P < .001), ACSAmid by 5.2 ± 5% (P < .001), and VOL by 5.0 ± 6.9% (P < .05) (values: means ± SD). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r = .82, P < .001 and r = .73, P < .001, respectively), and between MT and VOL (r = .76, P < .001 and r = .73, P < .001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r = .69, P < .01), but not % change in VOL (r = .33, P > .05). These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle.

Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes ±50 ng/ml IGF-I. Second, rat quadriceps (untrained, n = 9; 7-wk interval-"like" training, n = 13) were collected after ~3-wk D2O (70 atom %) administration, with body-water enrichment monitored via blood sampling. Finally, 10 (23 ± 1 yr) men consumed 150-ml D2O followed by 50 ml/wk and undertook 6-wk resistance exercise (6 × 8 repetitions, 75% 1-repetition maximum 3/wk) with body-water enrichment monitored by saliva sampling and muscle biopsies (for determination of RNA synthesis) at 0, 3, and 6 wk. Ribose mole percent excess (r-MPE) from purine nucleotides was analyzed via GC-MS/MS. Proliferating C2C12 cell r-MPE exhibited a rise to plateau, whereas IGF-I increased myotube RNA from 76 ± 3 to 123 ± 3 ng/µl and r-MPE by 0.39 ± 0.1% (both P < 0.01). After 3 wk, rat quadriceps r-MPE had increased to 0.25 ± 0.01% (P < 0.01) and was greater with running exercise (0.36 ± 0.02%; P < 0.01). Human muscle r-MPE increased to 0.06 ± 0.01 and 0.13 ± 0.02% at 3/6 wk, respectively, equating to synthesis rates of ~0.8%/day, increasing with resistance exercise to 1.7 ± 0.3%/day (P < 0.01) and 1.2 ± 0.1%/day (P < 0.05) at 3/6 wk, respectively. Therefore, we have developed and physiologically validated a novel technique to explore ribosomal biogenesis in a multimodal fashion.

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.

KEY POINTS: This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate-intensity exercise. Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two-legged dynamic knee-extensor moderate-intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise. Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise. Using a combined whole-leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms. ABSTRACT: Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate-intensity exercise in young (n = 17; 23 ± 1 years old) and older men (n = 15; 68 ± 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two-legged isolated knee-extensor exercise at 20 ± 1 W (∼50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl-CoA carboxylase 2 and AMP-activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane-associated fatty acid binding protein and AMPKγ3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole-leg and molecular differences in fatty acid mobilization could explain the age- and immobilization-induced IMTG accumulation.

Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training.

We sought to ascertain the time course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naive individuals and determine whether the magnitude of response was associated with exercise-induced muscle damage. Sixteen RE naive men were recruited; eight underwent two sessions of 5 × 30 maximum isokinetic knee extensions (180°/s) separated by 48 h. Muscle biopsies of the vastus lateralis, obtained from different sites, were taken at baseline and 24 h after each exercise bout. Eight individuals acted as nonexercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray and protein levels of heat shock protein (HSP) 27 and αB-crystallin in muscle cross sections by immunohistochemistry as a proxy measure of muscle damage. In control subjects, no probe sets were significantly altered (false discovery rate < 0.05), and HSP27 and αB-crystallin protein remained unchanged throughout the study. In exercised subjects, significant intersubject variability following the initial RE bout was observed in the muscle transcriptome, with greatest changes occurring in subjects with elevated HSP27 and αB-crystallin protein. Following the second bout, the transcriptome response was more consistent, revealing a cohort of probe sets associated with immune activation, the suppression of oxidative metabolism, and ubiquitination, as differentially regulated. The results reveal that the initial transcriptional response to RE is variable in RE naive volunteers, potentially associated with muscle damage and unlikely to reflect longer term adaptations to RE training. These results highlight the importance of considering multiple time points when determining the transcriptional response to RE and associated physiological adaptation.

Resistance exercise and the mechanisms of muscle mass regulation in humans: acute effects on muscle protein turnover and the gaps in our understanding of chronic resistance exercise training adaptation.

Increasing muscle mass is important when attempting to maximize sports performance and achieve physique augmentation. However, the preservation of muscle mass is essential to maintaining mobility and quality of life with aging, and also impacts on our capacity to recover from illness. Nevertheless, our understanding of the processes that regulate muscle mass in humans during resistance exercise training, chronic disuse and rehabilitation training following atrophy remains very unclear. Here, we report on some of the recent developments in the study of those processes thought to be responsible for governing human muscle protein turnover in response to intense physical activity. Specifically, the effects of acute and chronic resistance exercise in healthy volunteers and also in response to rehabilitation resistance exercise training following muscle atrophy will be discussed, with discrepancies and gaps in our understanding highlighted. In particular, ubiquitin-proteasome mediated muscle proteolysis (Muscle Atrophy F-box/Atrogin-1 and Muscle RING Finger 1), translation initiation of muscle protein synthesis (mammalian target of rapamycin signaling), and satellite cell mediated myogenesis are highlighted as pathways of special relevance to muscle protein metabolism in response to acute resistance exercise. Furthermore, research focused on quantifying signaling and molecular events that modulate muscle protein synthesis and protein degradation under conditions of chronic resistance training is highlighted as being urgently needed to improve knowledge gaps. These studies need to include multiple time-point measurements over the course of any training intervention and must include dynamic measurements of muscle protein synthesis and degradation and sensitive measures of muscle mass. This article is part of a Directed Issue entitled Molecular basis of muscle wasting.

Effect of whey protein- and carbohydrate-enriched diet on glycogen resynthesis during the first 48 h after a soccer game.

The effect of a whey protein- and carbohydrate (CHO)-enriched diet on the rate of muscle glycogen resynthesis after a soccer match was examined. Sixteen elite soccer players were randomly assigned to a group ingesting a diet rich in carbohydrates and whey protein [CHO, protein, and fat content was 71, 21, and 8E%, respectively; high content of carbohydrates and whey protein (HCP), n = 9] or a group ingesting a normal diet (55, 18, and 26E%; control [CON], n = 7) during a 48-h recovery period after a soccer match. CON and three additional players carried out a 90- and 60-min simulated match without body contacts (SIM90 and SIM60). Muscle glycogen was lowered (P < 0.05) by 54, 48, 53, and 38% after the matches in CON, HCP, SIM90, and SIM60, respectively. Glycogen resynthesis during the first 48 h after the match was not different between CON and HCP, whereas glycogen resynthesis was slower (P < 0.05) during the first 24 h after SIM60 than SIM90 (2.88 ± 0.84 vs 4.32 ± 0.54 mmol/kg dw/h). In HCP, glycogen content in type II muscle fibers was still lowered 48 h after the match. In conclusion, glycogen resynthesis 48 h after a soccer match is not elevated by ingestion of a HCP diet. Furthermore, glycogen resynthesis does not appear to be impaired by body contacts during a match.

Dietary supplements for athletes: emerging trends and recurring themes.

Dietary supplements are widely used at all levels of sport. Changes in patterns of supplement use are taking place against a background of changes in the regulatory framework that governs the manufacture and distribution of supplements in the major markets. Market regulation is complicated by the increasing popularity of Internet sales. The need for quality control of products to ensure they contain the listed ingredients in the stated amount and to ensure the absence of potentially harmful substances is recognized. This latter category includes compounds prohibited under anti-doping regulations. Several certification programmes now provide testing facilities for manufacturers of both raw ingredients and end products to ensure the absence of prohibited substances. Athletes should carry out a cost-benefit analysis for any supplement they propose to use. For most supplements, the evidence is weak, or even completely absent. A few supplements, including caffeine, creatine, and bicarbonate, are supported by a strong research base. Difficulties arise when new evidence appears to support novel supplements: in recent years, ß-alanine has become popular, and the use of nitrate and arginine is growing. Athletes seldom wait until there is convincing evidence of efficacy or of safety, but caution is necessary to minimize risk.

Optimization of insulin-mediated creatine retention during creatine feeding in humans.

The aim of this study was to determine whether creatine ingested in combination with relatively small quantities of essential amino acids, simple sugars, and protein would stimulate insulin release and augment whole-body creatine retention to the same extent as a large bolus of simple sugars. Seven young, healthy males underwent three randomized, 3-day experimental trials. Each day, 24-h urine collections were made, and on the second day participants received 5 g creatine + water (creatine trial), 5 g creatine + approximately 95 g dextrose (creatine + carbohydrate) or 5 g creatine + 14 g protein hydrolysate, 7 g leucine, 7 g phenylalanine, and 57 g dextrose (creatine + protein, amino acids, and carbohydrate) via naso-gastric tube at three equally spaced intervals. Blood samples were collected at predetermined intervals after the first and third naso-gastric bolus. After administration of the first and third bolus, serum insulin concentration was increased by 15 min (P < 0.05) in the creatine + carbohydrate and creatine + protein, amino acids, and carbohydrate trials compared with creatine alone, and plasma creatine increased more following creatine alone (15 min, P < 0.05) than in the creatine + carbohydrate and creatine + protein, amino acids, and carbohydrate trials. Urinary creatine excretion was greater with creatine alone (P < 0.05) than with creatine + carbohydrate and creatine + protein, amino acids, and carbohydrate. Administration of creatine + protein, amino acids, and carbohydrate can stimulate insulin release and augment whole-body creatine retention to the same extent as when larger quantities of simple sugars are ingested.

The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy.

Skeletal muscle exhibits great plasticity in response to altered activity levels, ultimately resulting in tissue remodelling and substantial changes in mass. Animal research would suggest that the ubiquitin proteasome system, in particular the ubiquitin ligases MAFbx/atrogin-1 and MuRF1, are instrumental to the processes underlying these changes. This review article therefore examines the role of proteasomal-mediated protein degradation in human skeletal muscle in health and disease. Specifically, the effects of exercise, disuse and inflammatory disease states on the ubiquitin proteasome system in human skeletal muscle are examined. The article also identifies several inconsistencies between published human studies and data obtained from animal models of muscle atrophy, highlighting the need for a more comprehensive examination of the molecular events responsible for modulating muscle mass in humans.

Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle.

We determined the effects of intravenous infusion of amino acids (AA) at serum insulin of 5, 30, 72, and 167 mU/l on anabolic signaling, expression of ubiquitin-proteasome components, and protein turnover in muscles of healthy young men. Tripling AA availability at 5 mU/l insulin doubled incorporation of [1-(13)C]leucine [i.e., muscle protein synthesis (MPS), P < 0.01] without affecting the rate of leg protein breakdown (LPB; appearance of d(5)-phenylalanine). While keeping AA availability constant, increasing insulin to 30 mU/l halved LPB (P < 0.05) without further inhibition at higher doses, whereas rates of MPS were identical to that at 5 mU/l insulin. The phosphorylation of PKB Ser(473) and p70(S6k) Thr(389) increased concomitantly with insulin, but whereas raising insulin to 30 mU/l increased the phosphorylation of mTOR Ser(2448), 4E-BP1 Thr(37/46), or GSK3beta Ser(9) and decreased that of eEF2 Thr(56), higher insulin doses to 72 and 167 mU/l did not augment these latter responses. MAFbx and proteasome C2 subunit proteins declined as insulin increased, with MuRF-1 expression largely unchanged. Thus increasing AA and insulin availability causes changes in anabolic signaling and amounts of enzymes of the ubiquitin-proteasome pathway, which cannot be easily reconciled with observed effects on MPS or LPB.

Temporal changes in the involvement of pyruvate dehydrogenase complex in muscle lactate accumulation during lipopolysaccharide infusion in rats.

A characteristic manifestation of sepsis is muscle lactate accumulation. This study examined any putative (causative) association between pyruvate dehydrogenase complex (PDC) inhibition and lactate accumulation in the extensor digitorum longus (EDL) muscle of rats infused with lipopolysaccharide (LPS), and explored the involvement of increased transcription of muscle-specific pyruvate dehydrogenase kinase (PDK) isoenzymes. Conscious, male Sprague-Dawley rats were infused i.v. with saline (0.4 ml h(-1), control) or LPS (150 mug kg(-1) h(-1)) for 2 h, 6 h or 24 h (n = 6-8). Muscle lactate concentration was elevated after 2, 6 and 24 h LPS infusion. Muscle PDC activity was the same at 2 h and 6 h, but was 65% lower after 24 h of LPS infusion (P < 0.01), when there was a 47% decrease in acetylcarnitine concentration (P < 0.05), and a 24-fold increase in PDK4 mRNA expression (P < 0.001). These changes were preceded by marked increases in tumour necrosis factor-alpha and interleukin-6 mRNA expression at 2 h. The findings indicate that the early (2 and 6 h) elevation in muscle lactate concentration during LPS infusion was not attributable to limited muscle oxygen availability or ATP production (evidenced by unchanged ATP and phosphocreatine (PCr) concentrations) or to PDC inhibition, whereas after 24 h, muscle lactate accumulation appears to have resulted from PDC activation status limiting pyruvate flux, most probably due to cytokine-mediated up-regulation of PDK4 transcription.

The plasma ammonia response to cycle exercise in COPD.

The plasma ammonia response to exercise in chronic obstructive pulmonary disease (COPD) was examined and the relationship between plasma ammonia concentration and muscle adenine nucleotide metabolism was explored. In total, 25 stable COPD patients and 13 similar-aged controls underwent incremental and constant-work rate cycle exercise tests. Arterialised venous blood was sampled at rest, at 1-min intervals during exercise and

Dietary supplements for football.

Physical training and competition in football markedly increase the need for macro- and micronutrient intake. This requirement can generally be met by dietary management without the need for dietary supplements. In fact, the efficacy of most supplements available on the market is unproven. In addition, players must be cautious of inadequate product labelling and supplement impurities that may cause a positive drug test. Nonetheless, a number of dietary supplements may beneficially affect football performance. A high endurance capacity is a prerequisite for optimal match performance, particularly if extra time is played. In this context, the potential of low-dose caffeine ingestion (2 - 5 mg . kg body mass(-1)) to enhance endurance performance is well established. However, in the case of football, care must be taken not to overdose because visual information processing might be impaired. Scoring and preventing goals as a rule requires production of high power output. Dietary creatine supplementation (loading dose: 15 - 20 g . day(-1), 4 - 5 days; maintenance dose: 2 - 5 g g . day(-1)) has been found to increase muscle power output, especially during intermittent sprint exercises. Furthermore, creatine intake can augment muscle adaptations to resistance training. Team success and performance also depend on player availability, and thus injury prevention and health maintenance. Glucosamine or chondroitin may be useful in the treatment of joint pain and osteoarthritis, but there is no evidence to support the view that the administration of these supplements will be preventative. Ephedra-containing weight-loss cocktails should certainly be avoided due to reported adverse health effects and positive doping outcomes. Finally, the efficacy of antioxidant or vitamin C intake in excess of the normal recommended dietary dose is equivocal. Responses to dietary supplements can vary substantially between individuals, and therefore the ingestion of any supplement must be assessed in training before being used in competition. It is recommended that dietary supplements are only used based on the advice of a qualified sports nutrition professional.