Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model.

Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.

Pre-season in soccer: a paradox between a high volume of technical/tactical training and improvement in the neuromuscular performance of elite women soccer players.

BACKGROUND: there is a paradox between the development of strength-power abilities and the high volume of technical/tactical training in elite soccer players during the pre-season. This concurrent effect between aerobic and neuromuscular training regimes induce impairment in power performance. METHODS: this study aimed to investigate the effect of an equalized program of strength-power training (4-5 sessions/week) and soccer training (4-6 sessions/week) in power and aerobic performance during 8-weeks of pre-season in elite women soccer players. Vertical jumps [squat jump (SJ); countermovement jump (CMJ)] and Yo-Yo intermittent recovery level 1 test (YOYO-R1) were assessed pre- and post pre-season. A paired sample t-test was used to compare differences between pre and post pre-season (Δ%). The level of significance was established at p ≤ 0.05. RESULTS: the women soccer players improved the SJ (p<0.001; Δ%=12), CMJ (p<0.001; Δ%=8.5), and YOYO-R1 (p<0.001; Δ% =28.5). There was a body recomposition observed, lower body fat (p = 0.004; Δ%=15), higher fat free mass (p = 0.001; Δ%=5). CONCLUSIONS: our results demonstrated that it is possible to develop aerobic and power abilities of elite women soccer players during pre-season using an equalized ratio of soccer training and strength-power training schedules.

Reduced Endurance Capacity and Suboptimal Energy Availability in Top-Level Female Cyclists.

PURPOSE: Women's professional cycling has grown in popularity, and this increase is also apparent in Brazil, which has increased its female cycling calendar in recent years. The aim of this observational study was to (1) determine training and competition loads of a top-level Brazilian female cycling team, (2) evaluate nutrition and clinical health, and (3) measure whether exercise capacity changed throughout the season. METHODS: Training and competition data were collected over the season using global positioning system monitors, while laboratory-based physiological and performance measures (incremental cycling test, 30-s Wingate, 4-km time trial) and clinical and nutritional analyses were performed at time points throughout the season. RESULTS: Total distance covered over the year was 11,124 (2895) km (7382-14,698 km). Endurance capacity was reduced over the season (P = .005) but not anaerobic power (all P > .05). Nutrition and stress markers remained largely unchanged throughout the season, although there were some individual fluctuations in some measures, and testosterone concentration was low for some. Median estimated energy availability ranged between 32.3 and 56.8 kcal·kgLBM-1·d-1 during training and 26.4 and 53.8 kcal·kgLBM-1·d-1 during competition. Percentage of training spent in optimal estimated energy availability was generally low, with 3 athletes spending <35% within the optimal intake. CONCLUSIONS: Substantial training and competition loads of the monitored professional Brazilian female cyclists may have reduced exercise capacity toward the end of the season, indicative of a grueling yearlong schedule. Several athletes may have had suboptimal energy availability during the season, potentially affecting testosterone concentration. These data demonstrate the difficulties in maintaining optimal nutrition, health, and performance throughout a season in professional female cycling and highlight the need for quality sport-science support for this type of top-level athlete.

Correction to: Is Open-Label Placebo a New Ergogenic Aid? A Commentary on Existing Studies and Guidelines for Future Research.

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Insulin does not stimulate ß-alanine transport into human skeletal muscle.

To test whether high circulating insulin concentrations influence the transport of ß-alanine into skeletal muscle at either saturating or subsaturating ß-alanine concentrations, we conducted two experiments whereby ß-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of ß-alanine intravenously (0.11 g·kg-1·min-1 for 150 min), with or without insulin infusion. ß-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and ß-alanine analyses. ß-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of ß-alanine (10 mg/kg) before insulin infusion or no infusion. ß-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma ß-alanine, muscle ß-alanine, muscle carnosine and urinary ß-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma ß-alanine or muscle ß-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase ß-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of ß-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize ß-alanine transport into muscle following ß-alanine intake.

"I put it in my head that the supplement would help me": Open-placebo improves exercise performance in female cyclists.

This study investigated the effect of open-placebo on cycling time-trial (TT) performance. Twenty-eight trained female cyclists completed a 1-km cycling TT following a control session or an open-placebo intervention. The intervention consisted of an individual presentation, provided by a medic, in which the concept of open-placebo was explained to the participant, before she ingested two red and white capsules containing flour; 15 min later, they performed the TT. In the control session, the participant sat quietly for 20 min. Heart rate and ratings of perceived exertion (RPE) were monitored throughout exercise, while blood lactate was determined pre- and post-exercise. Post-exercise questionnaires were employed to gain insight into the perceived influence of the supplement on performance. Open-placebo improved time-to-completion (P = 0.039, 103.6±5.0 vs. 104.4±5.1 s, -0.7±1.8 s, -0.7±1.7%) and mean power output (P = 0.01, 244.8±34.7 vs. 239.7±33.2, +5.1±9.5 W) during the TT. Individual data analysis showed that 11 individuals improved, 13 remained unchanged and 4 worsened their performance with open-placebo. Heart rate, RPE and blood lactate were not different between sessions (all P>0.05). Positive expectation did not appear necessary to induce performance improvements, suggesting unconscious processes occurred, although a lack of an improvement appeared to be associated with a lack of belief. Open-placebo improved 1-km cycling TT performance in trained female cyclists. Although the intervention was successful for some individuals, individual variation was high, and some athletes did not respond or even performed worse. Thus, open-placebo interventions should be carefully considered by coaches and practitioners, while further studies are warranted.