Highlighting the idea of exerkines in the management of cancer patients with cachexia: novel insights and a critical review.

BACKGROUND: Exerkines are all peptides, metabolites, and nucleic acids released into the bloodstream during and after physical exercise. Exerkines liberated from skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (batokines), and neurons (neurokines) may benefit health and wellbeing. Cancer-related cachexia is a highly prevalent disorder characterized by weight loss with specific skeletal muscle and adipose tissue loss. Many studies have sought to provide exercise strategies for managing cachexia, focusing on musculoskeletal tissue changes. Therefore, understanding the responses of musculoskeletal and other tissue exerkines to acute and chronic exercise may provide novel insight and recommendations for physical training to counteract cancer-related cachexia. METHODS: For the purpose of conducting this study review, we made efforts to gather relevant studies and thoroughly discuss them to create a comprehensive overview. To achieve this, we conducted searches using appropriate keywords in various databases. Studies that were deemed irrelevant to the current research, not available in English, or lacking full-text access were excluded. Nevertheless, it is important to acknowledge the limited amount of research conducted in this specific field. RESULTS: In order to obtain a comprehensive understanding of the findings, we prioritized human studies in order to obtain results that closely align with the scope of the present study. However, in instances where human studies were limited or additional analysis was required to draw more robust conclusions, we also incorporated animal studies. Finally, 295 studies, discussed in this review. CONCLUSION: Our understanding of the underlying physiological mechanisms related to the significance of investigating exerkines in cancer cachexia is currently quite basic. Nonetheless, this demonstrated that resistance and aerobic exercise can contribute to the reduction and control of the disease in individuals with cancer cachexia, as well as in survivors, by inducing changes in exerkines.

The effects of regional quadriceps architecture on angle-specific rapid force expression.

Evaluating anatomical contributions to performance can increase understanding of muscle mechanics and guide physical preparation. While the impact of anatomy on muscular performance is well studied, the effects of regional quadriceps architecture on rapid torque or force expression are less clear. Regional (proximal, middle, and distal) quadriceps (vastus lateralis, rectus femoris, and vastus intermedius) thickness (MT), pennation angle (PA), and fascicle length (FL) of 24 males (48 limbs) were assessed via ultrasonography. Participants performed maximal isometric knee extensions at 40°, 70°, and 100° of knee flexion to evaluate rate of force development from 0 to 200 ms (RFD0-200). Measurements were repeated on three occasions with the greatest RFD0-200 and mean muscle architecture measures used for analysis. Linear regression models predicting angle-specific RFD0-200 from regional anatomy provided adjusted correlations (√adjR2) with bootstrapped compatibility limits. Mid-rectus femoris MT (√adjR2 = 0.41-0.51) and proximal vastus lateralis FL (√adjR2 = 0.42-0.48) were the best single predictors of RFD0-200, and the only measures to reach precision with 99% compatibility limits. Small simple correlations were found across all regions and joint angles between RFD0-200 and vastus lateralis MT (√adjR2 = 0.28 ± 0.13; mean ± SD), vastus lateralis FL (√adjR2 = 0.33 ± 0.10), rectus femoris MT (√adjR2 = 0.38 ± 0.10), and lateral vastus intermedius MT (√adjR2 = 0.24 ± 0.10). Between-correlation comparisons are reported within the article. Researchers should measure mid-region rectus femoris MT and vastus lateralis FL to efficiently and robustly evaluate potential anatomical contributions to rapid knee extension force changes, with distal and proximal measurements providing little additional value. However, correlations were generally small to moderate, suggesting that neurological factors may be critical in rapid force expression.

Variability of Multiangle Isometric Force-Time Characteristics in Trained Men.

ABSTRACT: Oranchuk, DJ, Storey, AG, Nelson, AR, Neville, JG, and Cronin, JB. Variability of multiangle isometric force-time characteristics in trained men. J Strength Cond Res 36(1): 284-288, 2022-Measurements of isometric force, rate of force development (RFD), and impulse are widely reported. However, little is known about the variability and reliability of these measurements at multiple angles, over repeated testing occasions in a homogenous, resistance-trained population. Thus, understanding the intersession variability of multiangle isometric force-time characteristics provides the purpose of this article. Three sessions of isometric knee extensions at 40°, 70°, and 100° of flexion were performed by 26 subjects across 51 limbs. All assessments were repeated on 3 occasions separated by 5-8 days. Variability was qualified by doubling the typical error of measurement (TEM), with thresholds of 0.2-0.6 (small), 0.6-1.2 (moderate), 1.2-2.0 (large), 2.0-4.0 (very large), and >4.0 (extremely large). In addition, variability was deemed large when the intraclass correlation coefficient (ICC) was <0.67 and coefficient of variation (CV) >10%; moderate when ICC >0.67 or CV <10% (but not both); and small when both ICC >0.67 and CV <10%. Small to moderate between-session variability (ICC = 0.68-0.95, CV = 5.2-18.7%, TEM = 0.24-0.49) was associated with isometric peak force, regardless of angle. Moderate to large variability was seen in early-stage (0-50 ms) RFD and impulse (ICC = 0.60-0.80, CV = 22.4-63.1%, TEM = 0.62-0.74). Impulse and RFD at 0-100 ms, 0-200 ms, and 100-200 ms were moderately variable (ICC = 0.71-0.89, CV = 11.8-42.1%, TEM = 0.38-0.60) at all joint angles. Isometric peak force and late-stage isometric RFD and impulse measurements were found to have low intersession variability regardless of joint angle. However, practitioners need to exercise caution when making inferences about early-stage RFD and impulse measures due to moderate-large variability.

Does ground-reaction force influence post-impact ball speed in the tennis forehand groundstroke?

Motion of the rear leg during a tennis forehand was previously reported to influence the ball speed. However, impact of a kinetic measure such as the ground-reaction force (GRF) on forehand ball speed has not been investigated. The aim of this study was to investigate the influence of GRF on forehand ball speed and identify the most influential component of GRF related to overall higher ball speeds. Nine tennis players (eight males, one female) were invited to participate. Three testing sessions were conducted. Each session consisted of maximal forehand ball-speed testing and seven forehands at three ball speeds; fast (100%), medium (90%) and slow (80%). GRF and post-impact ball speed were measured for each stroke. Of all the individual GRF vectors, peak anterior-posterior force best explained the changes in ball speed, where 26% (R2 = 0.26) of ball speed variance can be explained by this force vector alone. In a stepwise fashion, adding peak lateral force to the model explained a further 7% (R2 = 0.33). Combining peak anterior-posterior, medial-lateral and vertical forces explained a total of 37% (R2 = 0.37). Peak anterior-posterior force appears to be the most influential ground-reaction force affecting forehand post-impact ball speed.

Kinetic and kinematic profile of eccentric quasi-isometric loading.

Eccentric quasi-isometric (EQI) contractions (maintaining a yielding contraction for as long as possible, beyond task failure) have gained interest in research and applied settings. However, little is known regarding the biomechanical profile of EQIs. Fourteen well-trained males performed four maximal effort knee-extensor EQIs, separated by 180 seconds. Angular impulse, velocity, and time-under-tension through the 30-100º range of motion (ROM), and in eight ROM brackets were quantified. Statistical parametric mapping, analyses of variance, and standardised effects (Hedges' g (ES), %Δ) detected between-contraction joint-angle-specific differences in time-normalised and absolute variables. Mean velocity was 1.34º·s-1 with most (62.5 ± 4.9%) of the angular impulse imparted between 40-70º. Most between-contraction changes occurred between 30-50º (p≤ 0.067, ES = 0.53 ± 0.31, 60 ± 52%), while measures remained constant between 50-100º (= 0.069-0.83, ES = 0.10 ± 0.26, 14.3 ± 24.6%). EQIs are a time-efficient means to impart high cumulative mechanical tension, especially at short to medium muscle lengths. However, angular impulse distribution shifts towards medium to long muscle lengths with repeat contractions. Practitioners may utilise EQIs to emphasize the initial portion of the ROM, and limit ROM, or apply EQIs in a fatigued state to emphasize longer muscle lengths.

The effect of regional quadriceps anatomical parameters on angle-specific isometric torque expression.

The length-tension relationship affects knee extension performance; however, whether anatomical variations in different quadriceps regions affect this relationship is unknown. Regional (proximal, middle, distal) quadriceps thickness (MT), pennation angle, and fascicle length of 24 males (48 limbs) were assessed via ultrasonography. Participants also performed maximal voluntary isometric torque (MVIT) assessments at 40°, 70°, and 100° of knee flexion. Measures were recorded on 3 separate occasions. Linear regression models predicting angle-specific torque from regional anatomy provided adjusted simple and multiple correlations (√adjR2) with bootstrapped compatibility limits to assess magnitude. Middle vastus lateralis MT and MVIT at 100° (√adjR2 = 0.64) was the largest single correlation, with distal vastus lateralis MT having the greatest mean correlations regardless of angle (√adjR2 = 0.61 ± 0.05, mean ± SD). Lateral distal MT and architecture had larger (Δ√adjR2 = 0.01 to 0.43) single and multiple correlations with MVIT than the lateral proximal (√adjR2 = 0.15 to 0.69 vs -0.08 to 0.65). Conversely, middle anterior MT had greater (Δ√adjR2 = 0.08 to 0.38) single and multiple correlations than proximal MT (√adjR2 = 0.09 to 0.49 vs -0.21 to 0.14). The length-tension relationship was trivially affected by regional quadriceps architecture. The middle and distal quadriceps were the strongest predictors of MVIT at all joint angles. Therefore, researchers may wish to focus on middle and distal lateral quadriceps anatomy when performing ultrasonographic evaluations. Novelty: The length-tension relationship is minimally affected by regional quadriceps anatomical parameters. Middle and distal vastus lateralis and lateral vastus intermedius anatomy were consistently the best predictors of torque. Practitioners may focus their assessments on the middle and distal regions of the lateral quadriceps' musculature.

Short-term neuromuscular, morphological, and architectural responses to eccentric quasi-isometric muscle actions.

PURPOSE: Eccentric quasi-isometric (EQI) contractions have been proposed as a novel training method for safely exposing the musculotendinous system to a large mechanical load/impulse, with few repetitions. However, understanding of this contraction type is rudimentary. We aimed to compare the acute effects of a single session of isotonic EQIs with isokinetic eccentric (ECC) contractions. METHODS: Fifteen well-trained men performed a session of impulse-equated EQI and ECC knee extensions, with each limb randomly allocated to one contraction type. Immediately PRE, POST, 24/48/72 h, and 7 days post-exercise, regional soreness, quadriceps swelling, architecture, and echo intensity were evaluated. Peak concentric and isometric torque, rate of torque development (RTD), and angle-specific impulse were evaluated at each time point. RESULTS: There were substantial differences in the number of contractions (ECC: 100.8 ± 54; EQI: 3.85 ± 1.1) and peak torque (mean: ECC: 215 ± 54 Nm; EQI: 179 ± 28.5 Nm). Both conditions elicited similar responses in 21/53 evaluated variables. EQIs resulted in greater vastus intermedius swelling (7.1-8.8%, ES = 0.20-0.29), whereas ECC resulted in greater soreness at the distal and middle vastus lateralis and distal rectus femoris (16.5-30.4%, ES = 0.32-0.54) and larger echogenicity increases at the distal rectus femoris and lateral vastus intermedius (11.9-15.1%, ES = 0.26--0.54). Furthermore, ECC led to larger reductions in concentric (8.3-19.7%, ES = 0.45-0.62) and isometric (6.3-32.3%, ES = 0.18-0.70) torque and RTD at medium-long muscle lengths. CONCLUSION: A single session of EQIs resulted in less soreness and smaller reductions in peak torque and RTD versus impulse-equated ECC contractions, yet morphological shifts were largely similar. Long-term morphological, architectural, and neuromuscular adaptations to EQI training requires investigation.

Variability of regional quadriceps echo intensity in active young men with and without subcutaneous fat correction.

Quantifying echo intensity (EI), a proposed measure of muscle quality, is becoming increasingly popular. Additionally, much attention has been paid to regional differences in other ultrasonically evaluated measures of muscle morphology and architecture. However, the variability of regional (proximal, middle, distal) EI of the vastus lateralis, rectus femoris, and lateral and anterior vastus intermedius has yet to be determined. Twenty participants (40 limbs), were evaluated on 3 occasions, separated by 7 days. Intersession variability of EI with and without subcutaneous fat correction was quantified. Furthermore, the interchangeability of corrected EI across regions was evaluated. Variability of regional quadriceps EI was substantially lower with subcutaneous fat correction (intraclass correlation coefficient (ICC) = 0.81-0.98, coefficient of variation (CV) = 4.5%-16.8%, typical error of measure (TEM) = 0.13-0.49) versus raw values (ICC = 0.69-0.98, CV = 7.7%-42.7%, TEM = 0.14-0.68), especially when examining the vastus intermedius (ICC = 0.81-0.95, CV = 7.1%-16.8%, TEM = 0.23-0.49 vs. ICC = 0.69-0.92, CV = 22.9%-42.7%, TEM = 0.31-0.68). With the exception of the rectus femoris and vastus intermedius (p ≥ 0.143, effect size (ES) ≤ 0.18), corrected EI was greater for proximal and distal regions when compared with the midpoint (p ≤ 0.038, ES = 0.38-0.82). Researchers and practitioners should utilize subcutaneous fat thickness correction to confidently evaluate EI at all regions of the quadriceps. Regional EI cannot be used interchangeably for the vastus muscles, likely because of an increase in fibrous content towards the myotendinous junctions. Novelty Regional quadriceps echo intensity was reliable with and without correction for subcutaneous fat thickness. Intersession variability of regional quadriceps echo intensity was substantially improved following subcutaneous fat correction. Quadriceps echo intensity increased towards myotendinous junctions in the vastus muscles.

Variability of Regional Quadriceps Architecture in Trained Men Assessed by B-Mode and Extended-Field-of-View Ultrasonography.

PURPOSE: Regional muscle-architecture measures are reported widely; however, little is known about the variability of these measurements in the rectus femoris, vastus lateralis, and anterior and lateral vastus intermedius. The aim of this study was to quantify this variability. METHODS: Regional muscle thickness, pennation angle (PA), and calculated and extended-field-of-view-derived fascicle length (FL) were quantified in 26 participants using ultrasonography across 51 limbs on 3 occasions. To quantify variability, the typical error of measurement (TEM) was multiplied by 2, and thresholds of 0.2-0.6 (small), 0.6-1.2 (moderate), 1.2-2.0 (large), 2.0-4.0 (very large), and >4.0 (extremely large) were applied. In addition, variability was deemed large when the intraclass correlation coefficient (ICC) was <.67 and coefficient of variation (CV) >10%, moderate when ICC > .67 or CV < 10% (but not both), and small when both ICC > .67 and CV < 10%. RESULTS: Muscle thickness of all muscles and regions had low to moderate variability (ICC = .88-.98, CV = 2.4-9.3%, TEM = 0.15-0.47). PA of the proximal and distal vastus lateralis had low variability (ICC = .85-.96, CV = 3.8-8%) and moderate to large TEM (TEM = 0.42-0.83). PA of the rectus femoris was found to have moderate to very large variability (ICC = .38-.74, CV = 11.4-18.5%, TEM = 0.61-1.29) regardless of region. Extended-field-of-view-derived FL (ICC = .57-.94, CV = 4.1-11.5%, TEM = 0.26-0.88) was superior to calculated FL (ICC = .37-.84, CV = 7.4-17.9%, TEM = 0.44-1.33). CONCLUSIONS: Variability of muscle thickness was low in all quadriceps muscles and regions. Only rectus femoris PA and FL measurements were highly variable. The extended-field-of-view technique should be used to assess FL where possible. Inferences based on rectus femoris architecture should be interpreted with caution.

Variability of concentric angle-specific isokinetic torque and impulse assessments of the knee extensors.

OBJECTIVE: Length-tension relationships are widely reported in research, rehabilitation and performance settings; however, several isometric contractions at numerous angles are needed to understand these muscular outputs. Perhaps a more efficient way to determine torque-angle characteristics is via isokinetic dynamometry; however, little is known about the variability of isokinetic measurements besides peak torque and optimal angle. This paper examines the variability of angle-specific isokinetic torque and impulse measures. APPROACH: Three sessions of concentric (60°·s-1) knee extensions were performed by both limbs of 32 participants. Assessments were repeated on three occasions, separated by 5-8 d. To quantify variability, the standardized typical error of measurement (TEM) was doubled and thresholds of 0.2-0.6 (small), 0.6-1.2 (moderate), 1.2-2.0 (large), 2.0-4.0 (very large) and >4.0 (extremely large) were applied. Additionally, variability was deemed large when the intraclass correlation coefficient (ICC) was <0.67 and coefficient of variation (CV) > 10%; moderate when ICC > 0.67 or CV < 10% (but not both); and small when both ICC > 0.67 and CV < 10%. MAIN RESULTS: Isokinetic torque and angular impulse show small to medium variability (ICC = 0.75-0.96, CV = 6.4%-15.3%, TEM = 0.25-0.53) across all but the longest (100°) and shortest (10°) muscle lengths evaluated. However, moderate to large variability was found for the optimal angle (ICC = 0.58-0.64, CV = 7.3%-8%, TEM = 0.76-0.86), and torque and impulse at the beginning and end of the range of motion (ICC = 0.57-0.85, CV = 11-42.9%, TEM = 0.40-0.89). Intersession variability of isokinetic torque and impulse were small to moderate at medium (90-20°) joint angles. SIGNIFICANCE: Researchers and practitioners can examine the muscle torque-angle relationship and activity-specific torque outputs within these ranges, without resorting to more strenuous and time-consuming isometric evaluations.

Scientific Basis for Eccentric Quasi-Isometric Resistance Training: A Narrative Review.

Oranchuk, DJ, Storey, AG, Nelson, AR, and Cronin, JB. The scientific basis for eccentric quasi-isometric resistance training: A narrative review. J Strength Cond Res 33(10): 2846-2859, 2019-Eccentric quasi-isometric (EQI) resistance training involves holding a submaximal, yielding isometric contraction until fatigue causes muscle lengthening and then maximally resisting through a range of motion. Practitioners contend that EQI contractions are a powerful tool for the development of several physical qualities important to health and sports performance. In addition, several sports involve regular quasi-isometric contractions for optimal performance. Therefore, the primary objective of this review was to synthesize and critically analyze relevant biological, physiological, and biomechanical research and develop a rationale for the value of EQI training. In addition, this review offers potential practical applications and highlights future areas of research. Although there is a paucity of research investigating EQIs, the literature on responses to traditional contraction types is vast. Based on the relevant literature, EQIs may provide a practical means of increasing total volume, metabolite build-up, and hormonal signaling factors while safely enduring large quantities of mechanical tension with low levels of peak torque. Conversely, EQI contractions likely hold little neuromuscular specificity to high velocity or power movements. Therefore, EQI training seems to be effective for improving musculotendinous morphological and performance variables with low injury risk. Although speculative due to the limited specific literature, available evidence suggests a case for future experimentation.

Interunit Reliability and Effect of Data-Processing Methods of Global Positioning Systems.

PURPOSE: To establish the interunit reliability of a range of global positioning system (GPS)-derived movement indicators, to determine the variation between manufacturers, and to investigate the difference between software-derived and raw data. METHODS: A range of movement variables were obtained from 27 GPS units from 3 manufacturers (GPSports EVO, 10 Hz, n = 10; STATSports Apex, 10 Hz, n = 10; and Catapult S5, 10 Hz, n = 7) that measured the same team-sport simulation session while positioned on a sled. The interunit reliability was determined using the coefficient of variation (%) and 90% confidence limits, whereas between-manufacturers comparisons and comparisons of software versus raw processed data were established using standardized effect sizes and 90% confidence limits. RESULTS: The interunit reliability for both software and raw processed data ranged from good to poor (coefficient of variation = 0.2%; ±1.5% to 78.2%; ±1.5%), with distance, speed, and maximal speed exhibiting the best reliability. There were substantial differences between manufacturers, particularly for threshold-based acceleration and deceleration variables (effect sizes; ±90% confidence limits: -2.0; ±0.1 to 1.9; ±0.1), and there were substantial differences between data-processing methods for a range of movement indicators. CONCLUSIONS: The interunit reliability of most movement indicators was deemed as good regardless of processing method, suggesting that practitioners can have confidence within systems. Standardized data-processing methods are recommended, due to the large differences between data outputs from various manufacturer-derived software.

Isometric training and long-term adaptations: Effects of muscle length, intensity, and intent: A systematic review.

Isometric training is used in the rehabilitation and physical preparation of athletes, special populations, and the general public. However, little consensus exists regarding training guidelines for a variety of desired outcomes. Understanding the adaptive response to specific loading parameters would be of benefit to practitioners. The objective of this systematic review, therefore, was to detail the medium- to long-term adaptations of different types of isometric training on morphological, neurological, and performance variables. Exploration of the relevant subject matter was performed through MEDLINE, PubMed, SPORTDiscus, and CINAHL databases. English, full-text, peer-reviewed journal articles and unpublished doctoral dissertations investigating medium- to long-term (≥3 weeks) adaptations to isometric training in humans were identified. These studies were evaluated further for methodological quality. Twenty-six research outputs were reviewed. Isometric training at longer muscle lengths (0.86%-1.69%/week, ES = 0.03-0.09/week) produced greater muscular hypertrophy when compared to equal volumes of shorter muscle length training (0.08%-0.83%/week, ES = -0.003 to 0.07/week). Ballistic intent resulted in greater neuromuscular activation (1.04%-10.5%/week, ES = 0.02-0.31/week vs 1.64%-5.53%/week, ES = 0.03-0.20/week) and rapid force production (1.2%-13.4%/week, ES = 0.05-0.61/week vs 1.01%-8.13%/week, ES = 0.06-0.22/week). Substantial improvements in muscular hypertrophy and maximal force production were reported regardless of training intensity. High-intensity (≥70%) contractions are required for improving tendon structure and function. Additionally, long muscle length training results in greater transference to dynamic performance. Despite relatively few studies meeting the inclusion criteria, this review provides practitioners with insight into which isometric training variables (eg, joint angle, intensity, intent) to manipulate to achieve desired morphological and neuromuscular adaptations.

Psychological Responses to Acute Aerobic, Resistance, or Combined Exercise in Healthy and Overweight Individuals: A Systematic Review.

INTRODUCTION: Psychological distress and depression are risk factors for cardiovascular disease (CVD). As such, a reduction in psychological distress and increase in positive well-being may be important to reduce the risk for future development of CVD. Exercise training may be a good strategy to prevent and assist in the management of psychological disorders. The psychological effects of the initial exercise sessions may be important to increase exercise adherence. The aims of this systematic review were (a) to examine whether acute aerobic, resistance, or a combination of the 2 exercises improves psychological well-being and reduces psychological distress in individuals with healthy weight and those who are overweight/obese but free from psychological disorders, and (b) if so, to examine which form of exercise might yield superior results. METHODS: The online database PubMed was searched for articles using the PICO (patient, intervention, comparison, and outcome) framework for finding scientific journals based on key terms. RESULTS: Forty-two exercise studies met the inclusion criteria. A total of 2187 participants were included (age: 18-64 years, body mass index [BMI]: 21-39 kg/m2). Only 6 studies included participants with a BMI in the overweight/obese classification. Thirty-seven studies included aerobic exercise, 2 included resistance exercise, 1 used a combination of aerobic and resistance, and 2 compared the effects of acute aerobic exercise versus the effects of acute resistance exercise. The main findings of the review were that acute aerobic exercise improves positive well-being and have the potential to reduce psychological distress and could help reduce the risks of future CVD. However, due to the limited number of studies, it is still unclear which form of exercise yields superior psychological benefits. CONCLUSIONS: Obese, overweight, and healthy weight individuals can exhibit psychological benefits from exercise in a single acute exercise session, and these positive benefits of exercise should be used by health professionals as a tool to increase long-term participation in exercise in these populations.

Attenuation of Resting but Not Load-Mediated Protein Synthesis in Prostate Cancer Patients on Androgen Deprivation.

CONTEXT: Androgen deprivation therapy (ADT) is a common prostate cancer (PCa) treatment but results in muscular atrophy. Periodic increases in muscle protein synthesis (MPS) that occur after resistance exercise or protein intake may ameliorate this muscle loss, but the impact of these anabolic stimuli during ADT is unclear. OBJECTIVE: To determine the acute MPS response to whey protein supplementation with and without resistance exercise during ADT. DESIGN: Acute response in PCa patients vs age-matched controls (CON). SETTING: Academic laboratory setting. PARTICIPANTS: PCa patients on ADT (N = 8) and CON (N = 10). INTERVENTION: A standardized diet was consumed for 2 days prior to performing unilateral knee extension resistance exercise followed by ingestion of 40 g of whey protein. MAIN OUTCOME MEASURES: Bilateral biopsies and stable isotope infusions were used to determine MPS rates at rest after protein ingestion with and without resistance exercise. RESULTS: Baseline MPS during ADT was suppressed relative to CON (P = 0.01). Protein consumption stimulated MPS in both groups (approximate twofold increase, both P < 0.001), but to a greater extent in CON (P = 0.003). Protein plus resistance exercise increased MPS (∼3.4-fold increase, both P < 0.001) to a greater extent than did protein alone (P < 0.001), but with no difference between groups (P = 0.380). CONCLUSIONS: ADT reduces basal and protein feeding-induced rises in MPS; however, combined protein ingestion with resistance exercise stimulated MPS to a similar degree as CON. Testosterone appears to play a role in maintaining muscle mass but is not necessary to initiate a robust response in MPS following resistance exercise when combined with protein ingestion.

Protein-leucine ingestion activates a regenerative inflammo-myogenic transcriptome in skeletal muscle following intense endurance exercise.

Protein-leucine supplement ingestion following strenuous endurance exercise accentuates skeletal-muscle protein synthesis and adaptive molecular responses, but the underlying transcriptome is uncharacterized. In a randomized single-blind triple-crossover design, 12 trained men completed 100 min of high-intensity cycling then ingested 70/15/180/30 g protein-leucine-carbohydrate-fat (15LEU), 23/5/180/30 g (5LEU), or 0/0/274/30 g (CON) beverages during the first 90 min of a 240 min recovery period. Vastus lateralis muscle samples (30 and 240 min postexercise) underwent transcriptome analysis by microarray followed by bioinformatic analysis. Gene expression was regulated by protein-leucine in a dose-dependent manner affecting the inflammatory response and muscle growth and development. At 30 min, 15LEU and 5LEU vs. CON activated transcriptome networks with gene-set functions involving cell-cycle arrest (Z-score 2.0-2.7, P < 0.01), leukocyte maturation (1.7, P = 0.007), cell viability (2.4, P = 0.005), promyogenic networks encompassing myocyte differentiation and myogenin (MYOD1, MYOG), and a proteinaceous extracellular matrix, adhesion, and development program correlated with plasma lysine, arginine, tyrosine, taurine, glutamic acid, and asparagine concentrations. High protein-leucine dose (15LEU-5LEU) activated an IL-1I-centered proinflammatory network and leukocyte migration, differentiation, and survival functions (2.0-2.6, <0.001). By 240 min, the protein-leucine transcriptome was anti-inflammatory and promyogenic (IL-6, NF- ß, SMAD, STAT3 network inhibition), with overrepresented functions including decreased leukocyte migration and connective tissue development (-1.8-2.4, P < 0.01), increased apoptosis of myeloid and muscle cells (2.2-3.0, P < 0.002), and cell metabolism (2.0-2.4, P < 0.01). The analysis suggests protein-leucine ingestion modulates inflammatory-myogenic regenerative processes during skeletal muscle recovery from endurance exercise. Further cellular and translational research is warranted to validate amino acid-mediated myeloid and myocellular mechanisms within skeletal-muscle functional plasticity.

Protein-leucine fed dose effects on muscle protein synthesis after endurance exercise.

UNLABELLED: Protein-leucine ingestion after strenuous endurance exercise accentuates muscle protein synthesis and improves recovery of muscle performance. PURPOSE: The objective of this study is to determine whether a low-dose protein-leucine blend ingested after endurance exercise enhances skeletal muscle myofibrillar protein fractional synthetic rate (FSR). METHOD: In a crossover design, 12 trained men completed 100 min of high-intensity cycling, then ingested either 70/15/180/30 g of protein/leucine/carbohydrate/fat (15LEU), 23/5/180/30 g of 5LEU, or 0/0/274/30 g of CON beverages in randomized order in four servings during the first 90 min of a 240-min recovery period. Muscle biopsies were collected at 30 and 240 min into recovery with FSR determined by L-[ring-13C6]phenylalanine incorporation and mTORC1 pathway phosphorylation by Western blot. RESULTS: The 33% (90% CL, ±12%) increase in FSR with 5LEU (mean, SD: 0.080, 0.014%·h(-1)) versus CON (0.060, 0.012%·h(-1)) represented near-maximal FSR stimulation. Tripling protein-leucine dose (15LEU: 0.090, 0.11%·h(-1)) negligibly increased FSR (13%, ±12% vs 5LEU). Despite similar FSR, mTORC1(Ser2448) phosphorylation only increased with 15LEU at 30 min, whereas p70S6K(Thr389), rpS6(Ser240/244), and 4E-BP1γ(Ser112) phosphorylation increased with protein-leucine quantity at one or both time points. Plasma leucine and essential amino acid concentrations decreased during recovery in CON but increased with protein-leucine dose. Serum insulin was increased in 15LEU versus CON (60%, ±20%) but was unaffected relative to 5LEU. Regression analysis revealed p70S6K-rpS6 phosphorylation moderately predicted FSR, but the associations with plasma leucine and essential amino acids were small. CONCLUSIONS: Ingesting 23 g of protein with 5 g of added leucine achieved near-maximal FSR after endurance exercise, an effect unlikely attributable to mTORC1-S6K-rpS6 signaling, insulin, or amino acids. Translating the effects of protein-leucine quantity on protein synthesis to optimizing adaptation and performance requires further research.

Effect of post-exercise protein-leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling.

Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h(-1), respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h(-1)) beverages for 1-3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 (-)) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15-17 mmol O2 (-) cell(-1) ± 90 % confidence limits 20 mmol O2 (-) cell(-1)). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 (-) (33 ± 20 mmol O2 (-) cell(-1)), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein-leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on day 6, which could impact neutrophil-dependent processes during recovery from intense training.

A protein-leucine supplement increases branched-chain amino acid and nitrogen turnover but not performance.

PURPOSE: This study aimed to determine the effect of postexercise protein-leucine coingestion with CHO-lipid on subsequent high-intensity endurance performance and to investigate candidate mechanisms using stable isotope methods and metabolomics. METHODS: In this double-blind, randomized, crossover study, 12 male cyclists ingested a leucine/protein/CHO/fat supplement (LEUPRO 7.5/20/89/22 g · h(-1), respectively) or isocaloric CHO/fat control (119/22 g · h(-1)) 1-3 h after exercise during a 6-d training block (intense intervals, recovery, repeated-sprint performance rides). Daily protein intake was clamped at 1.9 g · kg(-1) · d(-1) (LEUPRO) and 1.5 g · kg(-1) · d(-1) (control). Stable isotope infusions (1-(13)C-leucine and 6,6-(2)H2-glucose), mass spectrometry-based metabolomics, and nitrogen balance methods were used to determine the effects of LEUPRO on whole-body branched-chain amino acid (BCAA) and glucose metabolism and protein turnover. RESULTS: After exercise, LEUPRO increased BCAA levels in plasma (2.6-fold; 90% confidence limits = ×/÷ 1.1) and urine (2.8-fold; ×/÷ 1.2) and increased products of BCAA metabolism plasma acylcarnitine C5 (3.0-fold; ×/÷ 0.9) and urinary leucine (3.6-fold; ×/÷ 1.3) and ß-aminoisobutyrate (3.4-fold; ×/÷ 1.4), indicating that ingesting ~10 g leucine per hour during recovery exceeds the capacity to metabolize BCAA. Furthermore, LEUPRO increased leucine oxidation (5.6-fold; ×/÷ 1.1) and nonoxidative disposal (4.8-fold; ×/÷ 1.1) and left leucine balance positive relative to control. With the exception of day 1 (LEUPRO = 17 ± 20 mg N · kg(-1), control = -90 ± 44 mg N · kg(-1)), subsequent (days 2-5) nitrogen balance was positive for both conditions (LEUPRO = 130 ± 110 mg N · kg(-1), control = 111 ± 86 mg N · kg(-1)). Compared with control feeding, LEUPRO lowered the serum creatine kinase concentration by 21%-25% (90% confidence limits = ± 14%), but the effect on sprint power was trivial (day 4 = 0.4% ± 1.0%, day 6 = -0.3% ± 1.0%). CONCLUSIONS: Postexercise protein-leucine supplementation saturates BCAA metabolism and attenuates tissue damage, but effects on subsequent intense endurance performance may be inconsequential under conditions of positive daily nitrogen balance.