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Oral ketone ester ingestion elevates circulating dopamine concentration during ultra-endurance exercise. This is associated with improved mental alertness. Furthermore, ketone ester intake inhibits postexercise skeletal muscle macrophage infiltration, and counteracts the increase in AMPK phosphorylation after exercise, which indicates improved muscular energy status.

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester ( R)-3-hydroxybutyl ( R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3-h intermittent cycling (IMT180′) followed by a 15-min time-trial (TT15′) and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen ([Formula: see text]) was gradually decreased from 18.6% to 14.5%. Before and during RACE, participants received either 1) 75 g of ketone ester (KE), 2) 300 mg/kg body mass bicarbonate (BIC), 3) KE + BIC, or 4) a control drink in addition to 60 g of carbohydrates/h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood ([Formula: see text]) and muscle oxygenation by ∼3%. In contrast, BIC decreased [Formula: see text] by ∼2% without impacting muscle oxygenation. Performance during TT15′ and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

We previously demonstrated that exogenous ketosis reduces urine production during exercise, however, the underlying physiological mechanism remained unclear. Here, we, for the first time demonstrate that exogenous ketosis suppresses the exercise-induced release of atrial natriuretic peptide (ANP). However, given the limited effects of ANP on renal haemodynamics during exercise, the underlying physiological mechanism remains unknown. But downregulation of ANP might explain a new physiological mechanism by which exogenous ketosis lowers blood-free fatty acid levels.

Sports nutrition science seeks to determine optimal dietary protocols for athletes pushing the limits of human physiology in power, endurance, and skill. Traditionally, dietary interventions aimed to stimulate performance have focused on strategic intake of carbohydrates, protein, and fat. However, recent development of oral ketone supplements has increased the popularity of intermitted exogenous ketosis (IEK) as a potential nutritional strategy to stimulate training adaptation and performance in athletes. Several physiologic mechanisms are implicated in acute modulation of exercise performance by IEK. These include use of ketone bodies as an alternative substrate for oxidative ATP production in contracting muscles and ketone-mediated inhibition of glycolytic flux. The latter could lead to glycogen sparing, which may increase endurance; on the other hand, glycolytic inhibition in conjunction with ketoacidosis could be ergolytic in short maximal exercise bouts. Furthermore, preliminary evidence suggests that acute and chronic post-exercise ketosis may stimulate recovery from training. Acute IEK could stimulate muscle protein synthesis and glycogen repletion, and chronic ketone ester intake blunted overreaching symptoms during short-term endurance training overload. This protection could be attributed to improved autonomic neural balance, appetite and stress hormone regulation, and possibly attenuation of exercise-induced inflammation and oxidative stress. Such effects could conceivably either down- or upregulate training adaptation. However, research to date describing both acute and chronic exogenous ketosis in exercise and training is limited and inconclusive. Further studies are required to elucidate the specific contexts and mechanisms whereby IEK could maximally benefit athletes.

PURPOSE: We recently reported that oral ketone ester (KE) intake before and during the initial 30 min of a 3 h 15 min simulated cycling race (RACE) transiently decreased blood pH and bicarbonate without affecting maximal performance in the final quarter of the event. We hypothesized that acid-base disturbances due to KE overrules the ergogenic potential of exogenous ketosis in endurance exercise. METHODS: Nine well-trained male cyclists participated in a similar RACE consisting of 3 h submaximal intermittent cycling (IMT180') followed by a 15-min time trial (TT15') preceding an all-out sprint at 175% of lactate threshold (SPRINT). In a randomized crossover design, participants received (i) 65 g KE, (ii) 300 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON), together with consistent 60 g·h-1 carbohydrate intake. RESULTS: KE ingestion transiently elevated blood D-ß-hydroxybutyrate to ~2-3 mM during the initial 2 h of RACE (P < 0.001 vs CON). In KE, blood pH concomitantly dropped from 7.43 to 7.36 whereas bicarbonate decreased from 25.5 to 20.5 mM (both P < 0.001 vs CON). Additional BIC resulted in 0.5 to 0.8 mM higher blood D-ß-hydroxybutyrate during the first half of IMT180' (P < 0.05 vs KE) and increased blood bicarbonate to 31.1 ± 1.8 mM and blood pH to 7.51 ± 0.03 by the end of IMT180' (P < 0.001 vs KE). Mean power output during TT15' was similar between KE, BIC, and CON at ~255 W but was 5% higher in KE + BIC (P = 0.02 vs CON). Time to exhaustion in the sprint was similar between all conditions at ~60 s (P = 0.88). Gastrointestinal symptoms were similar between groups. DISCUSSION: The coingestion of oral bicarbonate and KE enhances high-intensity performance at the end of an endurance exercise event without causing gastrointestinal distress. ispartof: Medicine And Science In Sports And Exercise vol:53 issue:2 pages:431-441 ispartof: location:United States status: published

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. ispartof: Journal Of Applied Physiology vol:128 issue:6 pages:1643-1653 ispartof: location:United States status: published

PURPOSE: We recently demonstrated that coingestion of NaHCO3 to counteract ketoacidosis resulting from oral ketone ester (KE) intake improves mean power output during a 15-min time trial (TT) at the end of a 3-h cycling race by ~5%. This ergogenic effect occurred at a time when blood ketone levels were low, as ketosis was only induced during the initial ~2 h of the race. Therefore, in the current study, we investigated whether performance also increases if blood ketone levels are increased in the absence of ketoacidosis during high-intensity exercise. METHODS: In a double-blind crossover design, 14 well-trained male cyclists completed a 30-min TT (TT30') followed by an all-out sprint at 175% of lactate threshold (SPRINT). Subjects were randomized to receive (i) 50 g KE, (ii) 180 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON). RESULTS: KE ingestion increased blood d-ß-hydroxybutyrate to ~3-4 mM during the TT30' and SPRINT (P < 0.001 vs CON). In KE, blood pH and bicarbonate concomitantly dropped, causing 0.05 units lower pH and 2.6 mM lower bicarbonate in KE compared with CON during the TT30' and SPRINT (P < 0.001 vs CON). BIC coingestion resulted in 0.9 mM higher blood d-ß-hydroxybutyrate (P < 0.001 vs KE) and completely counteracted ketoacidosis during exercise (P > 0.05 vs CON). Mean power output during TT30' was similar between CON and BIC at 281 W, but was 1.5% lower in the KE conditions (main effect of KE: P = 0.03). Time to exhaustion in the SPRINT was ~64 s in CON and KE and increased by ~8% in the BIC conditions (main effect of BIC: P < 0.01). DISCUSSION: Neutralization of acid-base disturbance by BIC coingestion is insufficient to counteract the slightly negative effect of KE intake during high-intensity exercise. ispartof: Medicine And Science In Sports And Exercise vol:53 issue:5 pages:1-41 ispartof: location:United States status: Published online

The purpose of this study was to evaluate whether NaHCO3, administered via a 9-h stacked loading protocol (i.e. repeated supplementation with small doses in order to obtain a gradual increase in blood [HCO3 -]), has an ergogenic effect on repeated all-out exercise. Twelve physically active males were randomly assigned to receive either NaHCO3 (BIC) or placebo (PL) in a double-blind cross-over design. NaHCO3 supplementation was divided in three identical 3-h cycles: a 6.3 g bolus at the start, followed by 2.1 g doses at +1-h and +2-h, yielding a total NaHCO3 intake of 0.4 g·kg-1 BM over 9-h. At the end of each cycle, participants performed 2-min all-out cycling. Capillary blood samples were analyzed for [HCO3 -], pH and [La-]. Pre-exercise blood [HCO3 -] in PL decreased from 25.6±0.2 mmol·L-1 in bout 1 to 23.6±0.2 mmol·L-1 in bout 4, while increasing from 25.5±0.2 to 31.2±0.4 mmol·L-1 in BIC (P

Objectives Oral sodium bicarbonate intake (NaHCO3) may improve performance in short maximal exercise by inducing metabolic alkalosis. However, it remains unknown whether NaHCO3 also enhances all-out performance at the end of an endurance competition. Therefore, the present study investigated the effect of stacked NaHCO3 loading on sprint performance following a 3-h simulated cycling race. Design Double-blind randomized placebo-controlled cross-over study. Methods Eleven trained male cyclists (22.3 (18.3–25.3) year; 73.0 (61.5–88) kg; VO2max: 63.7 (57–72) ml kg−1 min−1) ingested either 300 mg kg−1 body weight NaHCO3 (BIC) or NaCl (PL). NaHCO3 or NaCl was supplemented prior to (150 mg kg−1) and during (150 mg kg−1) a 3-h simulated cycling race with a 90-s all-out sprint (90S) at the end. Capillary blood samples were collected for determination of blood pH, lactate and HCO3− concentrations. Analysis of variance (lactate, pH, HCO3−) and paired t-test (power) were applied to compare variables across condition (and time). Results NaHCO3 intake improved mean power during 90S by ∼3% (541 ± 59 W vs. 524 ± 57 W in PL, p = 0.047, Cohen’s D = 0.28, medium). Peak blood lactate concentration and heart rate at the end of 90S were higher (p

Due to lack of low-cost and convenient measurement procedures, uncontrolled changes in spontaneous physical activity (SPA) level often are insufficiently considered as a confounding factor in rodent studies. Nonetheless, alterations in SPA can significantly impact on a wide range of physiological measurements. Therefore, we developed an accurate, low-cost video tracking procedure to allow routine assessment of SPA in the home cage of experimental animals (i.e., mice) and in the absence of any distress that might cause alterations in SPA. SPA parameters acquired (movement distance, movement time, and movement speed) with the novel tracking system were identical to those simultaneously obtained with a high-end and well-validated movement-tracking device (mean error = 0.15 ± 0.07%, r = 0.99, P < 0.001). To further validate the setup, we also demonstrated caffeine-induced stimulation of SPA (195% more activity compared with vehicle, P < 0.01), we adequately reproduced typical SPA fluctuations inherent to day/night cycles (146 and 702% more active during nocturnal compared with diurnal cycle for Balb/c and C57BL/6J mice, respectively, P < 0.001), and we confirmed previously documented SPA differences between animal strains (24% less activity in C57BL/6J mice compared with Balb/c mice, P < 0.05). Taken together, we provide data to prove that this novel low-cost methodology can be conveniently used in any mouse experiment where uncontrolled changes in SPA due to experimental interventions might confound data interpretation. By analogy, the system can be used to document a beneficial impact of therapeutic interventions on SPA in any disease mouse model. NEW & NOTEWORTHY We developed a low-cost procedure to routinely measure SPA in mice. The procedure maintains normal SPA because the animals continue to stay in their home cage in the absence of any external manipulation by the investigators and under habitual dark/light ambient conditions. This novel methodology can be conveniently used in any mouse experiment to quantify experimentally induced alterations in SPA or to assess natural variations in SPA that might confound data interpretation. ispartof: J Appl Physiol (1985) vol:125 issue:2 pages:263-270 ispartof: location:United States status: published

The myocellular response to hypoxia is primarily regulated by hypoxia-inducible factors (HIFs). HIFs thus conceivably are implicated in muscular adaptation to altitude training. Therefore, we investigated the effect of hypoxic versus normoxic training during a period of prolonged hypoxia (‘living high’) on muscle HIF activation during acute ischaemia. Ten young male volunteers lived in normobaric hypoxia for 5 weeks (5 days per week, ~ 15.5 h per day, FiO2: 16.4–14.0%). One leg was trained in hypoxia (TRHYP, 12.3% FiO2) whilst the other leg was trained in normoxia (TRNOR, 20.9% FiO2). Training sessions (3 per week) consisted of intermittent unilateral knee extensions at 20–25% of the 1-repetition maximum. Before and after the intervention, a 10-min arterial occlusion and reperfusion of the leg was performed. Muscle oxygenation status was continuously measured by near-infrared spectroscopy. Biopsies were taken from m. vastus lateralis before and at the end of the occlusion. Irrespective of training, occlusion elevated the fraction of HIF-1α expressing myonuclei from ~ 54 to ~ 64% (P

ispartof: The Journal of Physiology vol:598 issue:21 pages:4749-4750 ispartof: location:England status: published

It is well known that elevated blood ketones attenuate net muscle protein breakdown, as well as negate catabolic events, during energy deficit. Therefore, we hypothesized that oral ketones can blunt endurance training-induced overreaching. Fit male subjects participated in two daily training sessions (3 weeks, 6 days/week) while receiving either a ketone ester (KE, n=9) or a control drink (CON, n=9) following each session. Sustainable training load in week 3, as well as power output in the final 30 min of a 2 h standardized endurance session were 15% higher in KE than in CON (both p

ispartof: JOURNAL OF PHYSIOLOGY-LONDON vol:597 issue:17 pages:4679-4680 ispartof: location:England status: published

To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans.Fifteen subjects were exposed for 4 h to normoxia (NOR) or to normobaric hypoxia (HYP, FiO2 = 0.11) in a randomized order 40 min after consumption of a high glycemic meal. A muscle biopsy from m. vastus lateralis and a blood sample were taken before (T0), after 1 h (T60) and 4 h (T240) in NOR or HYP and blood glucose levels were measured before exposure and every 30 min.In HYP, blood glucose was reduced 100 min (110.1 ± 5.4 in NOR vs 89.5 ± 4.7 mg dl(-1) in HYP) and 130 min (98.7 ± 3.8 in NOR vs 85.6 ± 4.9 mg dl(-1) in HYP) after completion of a meal, which resulted in an 83 % lower AUC in HYP compared to NOR (p = 0.006). This coincided with 40 % lower GLUT4 protein in the cytosolic fraction (p = 0.013) and a tendency to increase in the crude membrane fraction (p = 0.070) in HYP compared to NOR. At T240, blood glucose concentration was similar between HYP and NOR, whereas plasma insulin as well as phosphorylation of muscle Akt and GSK-3 was ~2-fold higher in HYP compared to NOR (p 0.05). In contrast, Rac1 protein was less abundant in the membrane fraction in HYP compared to NOR (p = 0.003), reflecting lower activation.Acute environmental hypoxia initially reduced blood glucose response to a meal, possibly via an increase in GLUT4 abundance at the sarcolemmal membrane. Later on, whole body insulin intolerance developed independently of defects in conventional insulin signaling in skeletal muscle.

Purpose: Ketone bodies are energy substrates produced by the liver during prolonged fasting or low-carbohydrate diet. The ingestion of a ketone ester (KE) rapidly increases blood ketone levels independent of nutritional status. KE has recently been shown to improve exercise performance, but whether it can also promote post-exercise muscle protein or glycogen synthesis is unknown. Methods: Eight healthy trained males participated in a randomized double-blind placebo-controlled crossover study. In each session, subjects undertook a bout of intense one-leg glycogen-depleting exercise followed by a 5-h recovery period during which they ingested a protein/carbohydrate mixture. Additionally, subjects ingested a ketone ester (KE) or an isocaloric placebo (PL). Results: KE intake did not affect muscle glycogen resynthesis, but more rapidly lowered post-exercise AMPK phosphorylation and resulted in higher mTORC1 activation, as evidenced by the higher phosphorylation of its main downstream targets S6K1 and 4E-BP1. As enhanced mTORC1 activation following KE suggests higher protein synthesis rates, we used myogenic C2C12 cells to further confirm that ketone bodies increase both leucine-mediated mTORC1 activation and protein synthesis in muscle cells. Conclusion: Our results indicate that adding KE to a standard post-exercise recovery beverage enhances the post-exercise activation of mTORC1 but does not affect muscle glycogen resynthesis in young healthy volunteers. In vitro, we confirmed that ketone bodies potentiate the increase in mTORC1 activation and protein synthesis in leucine-stimulated myotubes. Whether, chronic oral KE intake during recovery from exercise can facilitate training-induced muscular adaptation and remodeling need to be further investigated., Frontiers in Physiology, 8, ISSN:1664-042X

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of myocellular adaptation to exercise and hypoxia. However, the role of genetic factors in regulation of HIF-1 responses to exercise and hypoxia is unknown. We hypothesized that hypoxia at rest and during exercise stimulates the HIF-1 pathway and its downstream targets in energy metabolism regulation in a genotype-dependent manner. Eleven monozygotic twin (MZ) pairs performed an experimental trial in both normoxia and hypoxia (FiO2 10.7%). Biopsies were taken from m. vastus lateralis before and after a 20-min submaximal cycling bout @~30% of sea-level VO2max. Key-markers of the HIF-1 pathway and glycolytic and oxidative metabolism were analyzed using real-time PCR and Western Blot. Hypoxia increased HIF-1α protein expression by ~120% at rest vs. +150% during exercise (p < 0.05). Furthermore, hypoxia but not exercise increased muscle mRNA content of HIF-1α (+50%), PHD2 (+45%), pVHL (+45%; p < 0.05), PDK4 (+1200%), as well as PFK-M (+20%) and PPAR-γ1 (+60%; p < 0.05). Neither hypoxia nor exercise altered PHD1, LDH-A, PDH-A1, COX-4, and CS mRNA expressions. The hypoxic, but not normoxic exercise-induced increment of muscle HIF-1α mRNA content was about 10-fold more similar within MZ twins than between the twins (p < 0.05). Furthermore, in resting muscle the hypoxia-induced increments of muscle HIF-1α protein content, and HIF-1α and PDK4 mRNA content were about 3-4-fold more homogeneous within than between the twins pairs (p < 0.05). The present observations in monozygotic twins for the first time clearly indicate that the HIF-1α protein as well as mRNA responses to submaximal exercise in acute hypoxia are at least partly regulated by genetic factors. ispartof: Frontiers in Physiology vol:7 issue:JAN ispartof: location:Switzerland status: published

Androgens have well-established anabolic actions on skeletal muscle, although the direct effects of the androgen receptor (AR) in muscle remain unclear. We generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is selectively ablated in satellite cells, the muscle precursor cells. Total-limb maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles containing ∼10% more type I fibers and 10% less type IIa fibers than the corresponding control littermates. The weight of the perineal levator ani muscle is markedly reduced (-52%). Thus, muscle AR is involved in fiber-type distribution and force production of the limb muscles, while it is a major determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes (6-fold reduction in satARKO) through direct transcription activation by the AR. Consequently, muscle hypertrophy in response to androgens is augmented in Mstn-knockout mice. Our finding that androgens induce Mstn signaling to restrain their own anabolic actions has implications for the treatment of muscle wasting disorders.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C., Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P., Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

We investigated whether dietary nitrate (NO(3)(-)) supplementation enhances the effect of training in hypoxia on endurance performance at sea level. Twenty-two healthy male volunteers performed high-intensity endurance training on a cycle ergometer (6 weeks, 5×30 min/week at 4-6 mmol/L blood lactate) in normobaric hypoxia (12.5% FiO(2)), while ingesting either beetroot juice [0.07 mmol NO(3)(-) /kg body weight (bw)/day; BR, n = 11] or a control drink (CON, n = 11). During the pretest and the posttest, the subjects performed a 30-min simulated time trial (TT) and an incremental VO(2max) test. Furthermore, a biopsy was taken from m. vastus lateralis before and after the TT. Power output during the training sessions in both groups increased by ∼6% from week 1 to week 6 (P

UNLABELLED: Hypoxia-induced muscle wasting has been observed in several environmental and pathological conditions. However, the molecular mechanisms behind this loss of muscle mass are far from being completely elucidated, certainly in vivo. When studying the regulation of muscle mass by environmental hypoxia, many confounding factors have to be taken into account, such as decreased protein ingestion, sleep deprivation or reduced physical activity, which make difficult to know whether hypoxia per se causes a reduction in muscle mass. AIM: We hypothesized that acute exposure to normobaric hypoxia (11% O2 ) would repress the activation of the mTOR pathway usually observed after a meal and would activate the proteolytic pathways in skeletal muscle. METHODS: Fifteen subjects were exposed passively for 4 h to normoxic and hypoxic conditions in a random order after consumption of a light breakfast. A muscle biopsy and a blood sample were taken before, after 1 and 4 h of exposure. RESULTS: After 4 h, plasma insulin concentration and the phosphorylation state of PKB and S6K1 in skeletal muscle were higher in hypoxia than in normoxia (P

Skeletal muscle mitochondrial dysfunction is believed to play a role in the progression and severity of amyotrophic lateral sclerosis (ALS). The regulation of transcriptional co-activators involved in mitochondrial biogenesis and function in ALS is not well known. When compared with healthy control subjects, patients with ALS, but not neurogenic disease (ND), had lower levels of skeletal muscle peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA and protein and estrogen-related receptor-α (ERRα) and mitofusin-2 (Mfn2) mRNA. PGC-1β, nuclear respiratory factor-1 (NRF-1) and Mfn1 mRNA as well as cytochrome C oxidase subunit IV (COXIV) mRNA and protein were lower in patients with ALS and ND. Both patient groups had reductions in citrate synthase and cytochrome c oxidase activity. Similar observations were made in skeletal muscle from transgenic ALS G93A transgenic mice. In vitro, PGC-1α and PGC-1β regulated Mfn1 and Mfn2 in an ERRα-dependent manner. Compared to healthy controls, miRNA 23a, 29b, 206 and 455 were increased in skeletal muscle of ALS patients. miR-23a repressed PGC-1α translation in a 3' UTR dependent manner. Transgenic mice over expressing miR-23a had a reduction in PGC-1α, cytochome-b and COXIV protein levels. These results show that skeletal muscle mitochondrial dysfunction in ALS patients is associated with a reduction in PGC-1α signalling networks involved in mitochondrial biogenesis and function, as well as increases in several miRNAs potentially implicated in skeletal muscle and neuromuscular junction regeneration. As miR-23a negatively regulates PGC-1α signalling, therapeutic inhibition of miR-23a may be a strategy to rescue PGC-1α activity and ameliorate skeletal muscle mitochondrial function in ALS.

The aerodynamic drag of two drafting cyclists in upright position (UP), dropped position (DP) and time-trial position (TTP) is analysed by Computational Fluid Dynamics (CFD) simulations supported by wind-tunnel measurements. The CFD simulations are performed on high-resolution grids with grid cells of about 30 μm at the cyclist body surface, yielding y∗ values well below five. Simulations are made for single cyclists and for two drafting cyclists with bicycle separation distances (d) from 0.01 m to 1 m. Compared to a single (isolated) cyclist and for d = 0.01 m, the drag reduction of the trailing cyclist is 27.1%, 23.1% and 13.8% for UP, DP and TTP, respectively, while the drag reduction of the leading cyclist is 0.8%, 1.7% and 2.6% for UP, DP and TTP, respectively. The drag reductions decrease with increasing separation distance. Apart from the well-known drag reduction for the trailing cyclist, this study also confirms and quantifies the drag reduction for the leading cyclist. This effect was also confirmed by the wind-tunnel measurements: for DP with d = 0.15 m, the measured drag reduction of the leading cyclist was 1.6% versus 1.3% by CFD simulation. The CFD simulations are used to explain the aerodynamic drag effects by means of the detailed pressure distribution on and around the cyclists. It is shown that both drafting cyclists significantly influence the pressure distribution on each other’s body and the static pressure in the region between them, which governs the drag reduction experienced by each cyclist. These results imply that there is an optimum strategy for team time trials, which should be determined not only based on the power performance but also on the body geometry, rider sequence and the resulting aerodynamic drag of each team member. Similar studies can be performed for other sports such as skating, swimming and running.

Purpose: We investigated the effect of sprint interval training (SIT) in normoxia, vs. SIT in hypoxia alone or in conjunction with oral nitrate intake, on buffering capacity of homogenized muscle (βhm) and fiber type distribution, as well as on sprint and endurance performance. Methods: Twenty-seven moderately-trained participants were allocated to one of three experimental groups: SIT in normoxia (20.9% FiO2) + placebo (N), SIT in hypoxia (15% F +iO2) placebo (H), or SIT in hypoxia + nitrate supplementation (HN). All participated in 5 weeks of SIT on a cycle ergometer (30-s sprints interspersed by 4.5 min recovery-intervals, 3 weekly sessions, 4–6 sprints per session). Nitrate (6.45 mmol NaNO3) or placebo capsules were administered 3 h before each session. Before and after SIT participants performed an incremental VO2max-test, a 30-min simulated cycling time-trial, as well as a 30-s cycling sprint test. Muscle biopsies were taken from m. vastus lateralis. Results: SIT decreased the proportion of type IIx muscle fibers in all groups (P < 0.05). The relative number of type IIa fibers increased (P < 0.05) in HN (P < 0.05 vs. H), but not in the other groups. SIT had no significant effect on βhm. Compared with H, SIT tended to enhance 30-s sprint performance more in HN than in H (P = 0.085). VO2max and 30-min time-trial performance increased in all groups to a similar extent. Conclusion: SIT in hypoxia combined with nitrate supplementation increases the proportion of type IIa fibers in muscle, which may be associated with enhanced performance in short maximal exercise. Compared with normoxic training, hypoxic SIT does not alter βhm or endurance and sprinting exercise performance. ispartof: Frontiers in Physiology vol:7 issue:JUN ispartof: location:Switzerland status: published

Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis. ispartof: EUROPEAN JOURNAL OF TRANSLATIONAL MYOLOGY vol:26 issue:2 pages:67-75 ispartof: location:Italy status: published

Exercise tolerance is impaired in hypoxia, and it has recently been shown that dietary nitrate supplementation can reduce the oxygen (O2) cost of muscle contractions. Therefore, we investigated the effect of dietary nitrate supplementation on arterial, muscle, and cerebral oxygenation status, symptoms of acute mountain sickness (AMS), and exercise tolerance at simulated 5,000 m altitude. Fifteen young, healthy volunteers participated in three experimental sessions according to a crossover study design. From 6 days prior to each session, subjects received either beetroot (BR) juice delivering 0.07 mmol nitrate/kg body wt/day or a control drink (CON). One session was in normoxia with CON (NORCON); the two other sessions were in hypoxia (11% O2), with either CON (HYPCON) or BR (HYPBR). Subjects first cycled for 20 min at 45% of peak O2consumption (VO2peak; EX45%) and thereafter, performed a maximal incremental exercise test (EXmax). Whole-body VO2, arterial O2saturation (%SpO2) via pulsoximetry, and tissue oxygenation index of both muscle (TOIM) and cerebral (TOIC) tissue by near-infrared spectroscopy were measured. Hypoxia per se substantially reduced VO2peak, %SpO2, TOIM, and TOIC(NORCONvs. HYPCON, P < 0.05). Compared with HYPCON, VO2at rest and during EX45%was lower in HYPBR( P < 0.05), whereas %SpO2was higher ( P < 0.05). TOIMwas ∼4-5% higher in HYPBRthan in HYPCONboth at rest and during EX45%and EXmax( P < 0.05). TOICas well as the incidence of AMS symptoms were similar between HYPCONand HYPBRat any time. Hypoxia reduced time to exhaustion in EXmaxby 36% ( P < 0.05), but this ergolytic effect was partly negated by BR (+5%, P < 0.05). Short-term dietary nitrate supplementation improves arterial and muscle oxygenation status but not cerebral oxygenation status during exercise in severe hypoxia. This is associated with improved exercise tolerance against the background of a similar incidence of AMS.

The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a doubleblind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTTR), a 30-min cycling bout at ~75% VO2max, and another OGTT after exercise (OGTTEX). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTTR. Blood samples were collected before (t0) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTTEX an additional 75-g oral glucose bolus was administered at t60. In OGTTR, OFI administration reduced the area under the glucose curve (AUCGLUC) by 26%, mainly due to lower blood glucose levels at t30 and t60 (p < .05). Furthermore, a higher serum insulin concentration was noted after OFI intake at baseline and at t30 (p < .05). In OGTTEX, blood glucose at t60 was ~10% lower in OFI than in PL, which resulted in a decreased AUCGLUC (–37%, p < .05). However, insulin values and AUCINS were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

In secretory organs, such as the liver, the pancreas, and the adipose tissue, endoplasmic reticulum (ER) stress plays a key role in the etiology of cell disturbances implicated in many diseases. Although much less studied, ER stress also is present in skeletal muscle. In the present review, we hypothesize that ER stress may have important metabolic consequences in skeletal muscle. This review presents the situations in which ER stress is activated in skeletal muscle and its metabolic consequences.

The effect of creatine supplementation, alone or in combination with exercise training, on insulin sensitivity, intramyocellular lipid content (IMCL) and fatty acid translocase (FAT)/CD36 content was investigated in rats fed a sucrose-rich cafeteria diet during 12 weeks. Five experimental conditions were CON, receiving normal pellets; CAF, fed the cafeteria diet; CAF TR , fed the cafeteria diet together with exercise training in weeks 8–12 and CAF CR and CAF CRT that were analogous to CAF and CAF TR , respectively, but which received daily 2.5% of creatine monohydrate. During intravenous glucose tolerance test, compared with CON, whole-body glucose tolerance was reduced in CAF and CAF CR but not in CAF TR and CAF CRT . Insulin-stimulated glucose transport in perfused red gastrocnemius muscles was impaired in CAF and CAF CR but not in the trained groups. IMCL content in soleus and extensor digitorum longus muscles was higher in CAF than in CON, but not in CAF TR , CAF CR and CAF CRT . Compared with CON and CAF, FAT/CD36 protein content in m. soleus, was ∼40% lower in CAF CR , CAF TR and CAF CRT . The fraction of fecal fat, as determined in a 3-week post hoc study, was 25% higher in CAF CR than in CON. Moreover, in CAF CR , triglyceride concentration in blood and liver were significantly lower than in CAF. It is concluded that creatine supplementation in rats on a cafeteria diet inhibits IMCL accumulation via inhibition of gastrointestinal lipid absorption together with lower muscle FAT/CD36 content. Furthermore, exercise-induced but not creatine-induced reduction of IMCL is associated with improved insulin action on glucose transport in muscle cells.

AIM: In Western European populations, about 18% of all individuals have a complete deficiency of the alpha-actinin-3 protein owing to homozygosity for a stop codon mutation (R577X) in the ACTN3 gene. Actn3(-/-) knock-out mice show increased activity of multiple enzymes in the aerobic metabolic pathway in fast muscle fibres. Whether this observation is also present in human XX genotype carriers compared to RR carriers has not been studied in a fibre-type-specific approach in humans. The purpose of this study was therefore to compare fibre-type-specific oxidative enzyme activity in humans with a different ACTN3 R577X genotype. METHODS: Vastus lateralis muscle biopsy samples of 17 XX and 16 RR subjects were used to measure markers of oxidative capacity [cytochrome c oxidase (CYTOX) and succinate dehydrogenase (SDH)] in a fibre-type-specific assay using enzyme histochemistry. RESULTS: Cytochrome c oxidase staining showed no significant genotype group differences in type I or type II muscle fibres. Also, we found no significant differences in SDH staining of fast fibres comparing XX and RR carriers. CONCLUSION: In conclusion, the increase in oxidative enzyme activity of fast muscle fibres, as reported in an Actn3(-/-) knock-out mouse, was not observed in our human samples. Known differences in metabolic characteristics of muscle fibres in rodents compared to humans may in part explain this discrepancy in findings.

Summary Overt male hypogonadism induces not only osteoporosis but also unfavourable changes in body composition, which can be prevented by testosterone (T) replacement. In this preclinical study, the potential of synthetic androgen 7α-methyl-19-nortestosterone (MENT) as alternative treatment for male hypogonadism was evaluated in comparison with T. Eleven-month-old male rats were orchidectomized (orch) and left untreated for 2-months. Subsequently, the effects of 4-month MENT (12 μg/day) and T (72 μg/day) treatment on bone, muscle and fat were analysed using microcomputed tomography, dual-energy X-ray absorptiometry, dynamic bone histomorphometry and muscle fibre typing. At the onset of treatment, orch rats were clearly hypogonadal. This was evidenced by significant reductions of androgen-sensitive organ weight, lean mass, cortical thickness and trabecular bone volume compared with sham-operated aged-matched controls (sham). MENT and T restored weight of androgen-sensitive organs to a similar extent, with a superior anabolic action of MENT on levator ani muscle. Both androgens not only fully rescued hypogonadal loss of lean mass but also restored muscle fibre type composition and trabecular bone volume. Cortical bone loss was similarly prevented by MENT and T, but without full recovery to sham. Both androgens stimulated periosteal bone formation, but with a stronger effect of T. By contrast, MENT more strongly suppressed endocortical bone formation and bone turnover rate and reduced fat mass and serum leptin to a greater extent than T. MENT and T are both effective replacement therapies to stimulate bone and muscle in hypogonadal rats, with stronger lipolytic action of MENT.

In this study, we compared the effects of endurance training in the fasted state (F) vs. the fed state [ample carbohydrate intake (CHO)] on exercise-induced intramyocellular lipid (IMCL) and glycogen utilization during a 6-wk period of a hypercaloric (∼+30% kcal/day) fat-rich diet (HFD; 50% of kcal). Healthy male volunteers (18-25 yrs) received a HFD in conjunction with endurance training (four times, 60-90 min/wk) either in F (n = 10) or with CHO before and during exercise sessions (n = 10). The control group (n = 7) received a HFD without training and increased body weight by ∼3 kg (P < 0.001). Before and after a HFD, the subjects performed a 2-h constant-load bicycle exercise test in F at ∼70% maximal oxygen uptake rate. A HFD, both in the absence (F) or presence (CHO) of training, elevated basal IMCL content by ∼50% in type I and by ∼75% in type IIa fibers (P < 0.05). Independent of training in F or CHO, a HFD, as such, stimulated exercise-induced net IMCL breakdown by approximately twofold in type I and by approximately fourfold in type IIa fibers. Furthermore, exercise-induced net muscle glycogen breakdown was not significantly affected by a HFD. It is concluded that a HFD stimulates net IMCL degradation by increasing basal IMCL content during exercise in type I and especially IIa fibers. Furthermore, a hypercaloric HFD provides adequate amounts of carbohydrates to maintain high muscle glycogen content during training and does not impair exercise-induced muscle glycogen breakdown. ispartof: Journal of Applied Physiology vol:111 issue:1 pages:108-116 ispartof: location:United States status: published

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, β-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.

Nutrition is an important co-factor in exercise-induced training adaptations in muscle. We compared the effect of 6 weeks endurance training (3 days/week, 1-2 h at 75% VO(2peak)) in either the fasted state (F; n = 10) or in the high carbohydrate state (CHO, n = 10), on Ca(2+)-dependent intramyocellular signalling in young male volunteers. Subjects in CHO received a carbohydrate-rich breakfast before each training session, as well as ingested carbohydrates during exercise. Before (pretest) and after (posttest) the training period, subjects performed a 2 h constant-load exercise bout (~70% of pretest VO(2peak)) while ingesting carbohydrates (1 g/kg h(-1)). A muscle biopsy was taken from m. vastus lateralis immediately before and after the test, and after 4 h of recovery. Compared with pretest, in the posttest basal eukaryotic elongation factor 2 (eEF2) phosphorylation was elevated in CHO (P < 0.05), but not in F. In the pretest, exercise increased the degree of eEF2 phosphorylation about twofold (P < 0.05), and values returned to baseline within the 4 h recovery period in each group. However, in the posttest dephosphorylation of eEF2 was negated after recovery in CHO, but not in F. Independent of the dietary condition training enhanced the basal phosphorylation status of Phospholamban at Thr(17), 5'-AMP-activated protein kinase α (AMPKα), and Acetyl CoA carboxylase β (ACCβ), and abolished the exercise-induced increase of AMPKα and ACCβ (P < 0.05). In conclusion, training in the fasted state, compared with identical training with ample carbohydrate intake, facilitates post-exercise dephosphorylation of eEF2. This may contribute to rapid re-activation of muscle protein translation following endurance exercise. ispartof: European Journal of Applied Physiology vol:111 issue:7 pages:1297-1305 ispartof: location:Germany status: published

A fat-rich energy-dense diet is an important cause of insulin resistance. Stimulation of fat turnover in muscle cells during dietary fat challenge may contribute to maintenance of insulin sensitivity. Exercise in the fasted state markedly stimulates energy provision via fat oxidation. Therefore, we investigated whether exercise training in the fasted state is more potent than exercise in the fed state to rescue whole-body glucose tolerance and insulin sensitivity during a period of hyper-caloric fat-rich diet. Healthy male volunteers (18-25 y) received a hyper-caloric (∼+30% kcal day(-1)) fat-rich (50% of kcal) diet for 6 weeks. Some of the subjects performed endurance exercise training (4 days per week) in the fasted state (F; n = 10), whilst the others ingested carbohydrates before and during the training sessions (CHO; n = 10). The control group did not train (CON; n = 7). Body weight increased in CON (+3.0 ± 0.8 kg) and CHO (+1.4 ± 0.4 kg) (P < 0.01), but not in F (+0.7 ± 0.4 kg, P = 0.13). Compared with CON, F but not CHO enhanced whole-body glucose tolerance and the Matsuda insulin sensitivity index (P < 0.05). Muscle GLUT4 protein content was increased in F (+28%) compared with both CHO (P = 0.05) and CON (P < 0.05). Furthermore, only training in F elevated AMP-activated protein kinase α phosphorylation (+25%) as well as up-regulated fatty acid translocase/CD36 and carnitine palmitoyltransferase 1 mRNA levels compared with CON (∼+30%). High-fat diet increased intramyocellular lipid but not diacylglycerol and ceramide contents, either in the absence or presence of training. This study for the first time shows that fasted training is more potent than fed training to facilitate adaptations in muscle and to improve whole-body glucose tolerance and insulin sensitivity during hyper-caloric fat-rich diet.

The ACTN3 gene encodes for the alpha-actinin-3 protein, which has an important structural function in the Z line of the sarcomere in fast muscle fibers. A premature stop codon (R577X) polymorphism in the ACTN3 gene causes a complete loss of the protein in XX homozygotes. This study investigates a possible role for the alpha-actinin-3 protein in protecting the fast fiber from eccentric damage and studies repair mechanisms after a single eccentric exercise bout. Nineteen healthy young men (10 XX, 9 RR) performed 4 series of 20 maximal eccentric knee extensions with both legs. Blood (creatine kinase; CK) and muscle biopsy samples were taken to study differential expression of several anabolic (MyoD1, myogenin, MRF4, Myf5, IGF-1), catabolic (myostatin, MAFbx, and MURF-1), and contraction-induced muscle damage marker genes [cysteine- and glycine-rich protein 3 (CSRP3), CARP, HSP70, and IL-6] as well as a calcineurin signaling pathway marker (RCAN1). Baseline mRNA content of CSRP3 and MyoD1 was 49 + or - 12 and 67 + or - 25% higher in the XX compared with the RR group (P = 0.01-0.045). However, satellite cell number was not different between XX and RR individuals. After eccentric exercise, XX individuals tended to have higher serum CK activity (P = 0.10) and had higher pain scores than RR individuals. However, CSRP3 (P = 0.058) and MyoD1 (P = 0.08) mRNA expression tended to be higher after training in RR individuals compared with XX alpha-actinin-3-deficient subjects. This study suggests a protective role of alpha-actinin-3 protein in muscle damage after eccentric training and an improved stress-sensor signaling, although effects are small.

Objective: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. Design: Single centre double-blind randomized placebo controlled trial. Setting: Cardiac rehabilitation centre. Subjects and intervention: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. Main Measures: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. Results: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. Conclusion: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

The aim of this study was to compare the effects of a weight training program for the leg extensors with isokinetic cycling training (80 rpm) on maximal power output and endurance performance. Both strength training interventions were incorporated twice a week in a similar endurance training program of 12 weeks. Eighteen trained male cyclists (VO2peak 60 ± 1 ml kg−1 min−1) were grouped into the weight training (WT n = 9) or the isokinetic training group (IT n = 9) matched for training background and sprint power (P max), assessed from five maximal sprints (5 s) on an isokinetic bicycle ergometer at cadences between 40 and 120 rpm. Crank torque was measured (1 kHz) to determine the torque distribution during pedaling. Endurance performance was evaluated by measuring power, heart rate and lactate during a graded exercise test to exhaustion and a 30-min performance test. All tests were performed on subjects’ individual race bicycle. Knee extension torque was evaluated isometrically at 115° knee angle and dynamically at 200° s−1 using an isokinetic dynamometer. P max at 40 rpm increased in both the groups (~15%; P

This study aims at assessing the accuracy of computational fluid dynamics (CFD) for applications in sports aerodynamics, for example for drag predictions of swimmers, cyclists or skiers, by evaluating the applied numerical modelling techniques by means of detailed validation experiments. In this study, a wind-tunnel experiment on a scale model of a cyclist (scale 1:2) is presented. Apart from three-component forces and moments, also high-resolution surface pressure measurements on the scale model's surface, i.e. at 115 locations, are performed to provide detailed information on the flow field. These data are used to compare the performance of different turbulence-modelling techniques, such as steady Reynolds-averaged Navier-Stokes (RANS), with several k-epsilon and k-omega turbulence models, and unsteady large-eddy simulation (LES), and also boundary-layer modelling techniques, namely wall functions and low-Reynolds number modelling (LRNM). The commercial CFD code Fluent 6.3 is used for the simulations. The RANS shear-stress transport (SST) k-omega model shows the best overall performance, followed by the more computationally expensive LES. Furthermore, LRNM is clearly preferred over wall functions to model the boundary layer. This study showed that there are more accurate alternatives for evaluating flow around bluff bodies with CFD than the standard k-epsilon model combined with wall functions, which is often used in CFD studies in sports. ispartof: Journal of Biomechanics vol:43 issue:12 pages:2281-2287 ispartof: location:United States status: published

Purpose: Recent research has shown that chronic dietary [beta]-alanine ([beta]ALA) supplementation increases muscle carnosine content, which is associated with better performance in short (1-2 min) maximal exercise. Success in endurance competitions often depends on a final sprint. However, whether [beta]ALA can be ergogenic in sprint performance at the end of an endurance competition is at present unknown. Therefore, we investigated the effect of 8-wk [beta]ALA administration in moderately to well-trained cyclists on sprint performance at the end of a simulated endurance cycling race. Methods: A double-blind study was performed, which consisted of two experimental test sessions interspersed by an 8-wk [beta]ALA (2-4 g[middle dot]d-1; n = 9) or matched placebo (PL; n = 8) supplementation period. In the pretesting and the posttesting, subjects performed a 10-min time trial and a 30-s isokinetic sprint (100 rpm) after a 110-min simulated cycling race. Capillary blood samples were collected for determination of blood lactate concentration and pH. Results: Mean power output during the time trial was approximately 300 W and was similar between PL and [beta]ALA during either the pretesting or the posttesting. However, compared with PL, during the final sprint after the time trial, [beta]ALA on average increased peak power output by 11.4% (95% confidence interval = +7.8 to +14.9%, P = 0.0001), whereas mean power output increased by 5.0% (95% confidence interval = +2.0 to +8.1%, P = 0.005). Blood lactate and pH values were similar between groups at any time. Conclusion: Oral [beta]ALA supplementation can significantly enhance sprint performance at the end of an exhaustive endurance exercise bout.

SummaryObjectiveTo study the effect of frizzled-related protein (Frzb) deletion in mice on voluntary running wheel exercise performance and osteoarthritis.MethodsAt the age of 7 weeks, Frzb−/− and wild-type mice were grouped and a running wheel was introduced into the cage. At week 8, all mice were caged solitarily with a running wheel available. Mice were allowed free exercise for 6–12 months and distances run were recorded daily. Non-running mice were used as additional control group. X-rays of knees and hips were taken at different time points. At the end of the experiment, mice were sacrificed and joints were processed for histological evaluation. Cartilage damage, synovitis and osteophyte formation were scored. Muscle fiber composition of the soleus and extensor digitorum longus was studied by immunofluorescence.ResultsAt the age of 6 months, both female and male wild-type mice showed a significantly greater exercise performance than the Frzb−/− mice (P