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Abstract Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.

Abstract Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

Abstract Background The purpose of this study was to evaluate the effect of exhaustive exercise on proteins associated with muscle damage and regeneration, including IL-2, IL-4 and MyoD, in extensor digitorum longus (EDL) and soleus muscles and mesenteric (MEAT) and retroperitoneal adipose tissues (RPAT). Methods Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6) or 6 (E6 group, n = 6) hours after the exhaustion protocol, which consisted of running on a treadmill at approximately 70% of VO2max for fifty minutes and then at an elevated rate that increased at one m/min every minute, until exhaustion. Results The control group (C group, n = 6) was not subjected to exercise. IL-2 protein expression increased at E0 in the soleus and EDL; at E2, this cytokine returned to control levels in both tissues. In the soleus, IL-2 protein expression was lower than that in the control at E6. IL-4 protein levels increased in EDL at E6, but the opposite result was observed in the soleus. MyoD expression increased at E6 in EDL. Conclusion Exhaustive exercise was unable to modify IL-2 and IL-4 levels in MEAT and RPAT. The results show that exhaustive exercise has different effects depending on which muscle is analysed.

Abstract β-Hydroxy-β-methylbutyrate (HMβ) supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e.g., fat and liver) have not been examined. The purpose of this study was to evaluate the effects of HMβ supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HMβ (320 mg/kg body weight) or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HMβ supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL) and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR) and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.

Abstract Background The effects of chronic aerobic exercise upon lipid profile has been previously demonstrated, but few studies showed this effect under resistance exercise conditions. Objective The aim of this study was to examine the effects of different resistance exercise loads on blood lipids. Methods Thirty healthy, untrained male volunteers were allocated randomly into four groups based at different percentages of one repetition maximum (1 RM); 50%-1 RM, 75%-1 RM, 90%-1 RM, and 110%-1 RM. The total volume (sets × reps × load) of the exercise was equalized. The lipid profile (Triglycerides [TG], HDL-cholesterol [HDL-c], LDL-cholesterol, and Total cholesterol) was determined at rest and after 1, 24, 48 and 72 h of resistance exercise. Results The 75%-1 RM group demonstrated greater TG reduction when compared to other groups (p < 0.05). Additionally, the 110%-1 RM group presented an increased TG concentration when compared to 50% and 75% groups (p = 0.01, p = 0.01, respectively). HDL-c concentration was significantly greater after resistance exercise in 50%-1 RM and 75%-1 RM when compared to 110%-1 RM group (p = 0.004 and p = 0.03, respectively). Accordingly, the 50%-1 RM group had greater HDL-c concentration than 110%-1 RM group after 48 h (p = 0.05) and 72 h (p = 0.004), respectively. Finally, The 50% group has showed lesser LDL-c concentration than 110% group after 24 h (p = 0.007). No significant difference was found in Total Cholesterol concentrations. Conclusion These results indicate that the acute resistance exercise may induce changes in lipid profile in a specific-intensity manner. Overall, low and moderate exercise intensities appear to be promoting more benefits on lipid profile than high intensity. Long term studies should confirm these findings.

Abstract The purpose of present review is to describe the effect of leucine supplementation on skeletal muscle proteolysis suppression in both in vivo and in vitro studies. Most studies, using in vitro methodology, incubated skeletal muscles with leucine with different doses and the results suggests that there is a dose-dependent effect. The same responses can be observed in in vivo studies. Importantly, the leucine effects on skeletal muscle protein synthesis are not always connected to the inhibition of skeletal muscle proteolysis. As a matter of fact, high doses of leucine incubation can promote suppression of muscle proteolysis without additional effects on protein synthesis, and low leucine doses improve skeletal muscle protein ynthesis but have no effect on skeletal muscle proteolysis. These research findings may have an important clinical relevancy, because muscle loss in atrophic states would be reversed by specific leucine supplementation doses. Additionally, it has been clearly demonstrated that leucine administration suppresses skeletal muscle proteolysis in various catabolic states. Thus, if protein metabolism changes during different atrophic conditions, it is not surprising that the leucine dose-effect relationship must also change, according to atrophy or pathological state and catabolism magnitude. In conclusion, leucine has a potential role on attenuate skeletal muscle proteolysis. Future studies will help to sharpen the leucine efficacy on skeletal muscle protein degradation during several atrophic states.

Betaine supplementation, a dietary practice that possesses potential effects on exercise performance, has undergone extensive study. This study aimed to systematically review and meta-analyse betaine supplementation's effects on exercise performance. We searched PubMed, Web of Science, Scopus, and Google Scholar, focusing on studies comparing chronic betaine to a placebo in healthy humans aged 15-60 years, measuring exercise outcomes. Studies with acute betaine supplementation, no control group, or animals were excluded. Quality assessment was done using the Cochrane Risk of Bias Tool, and a random-effects model was employed for the meta-analysis. The review included 17 studies with 317 participants (21% female). The results revealed a significant effect size of 0.47 (95% CI 0.04 to 0.89) for maximal strength (1RM, 3RM, maximal isokinetic or isometric force), particularly in the lower body (SMD: 0.49, 95% CI 0.01 to 0.98). No significant effects were found for upper body strength, cycling sprint power, bench press throws power, or muscular endurance. However, vertical jumping performance improved significantly (SMD: 0.36, 95% CI 0.03 to 0.69) after excluding a low-quality study. In conclusion, betaine supplementation for at least 7 days significantly enhances muscular strength, especially lower body strength, and shows potential in improving vertical jumping performance.

To investigate the effects of 8-weeks of full versus split body resistance training (RT) on appetite and energy intake in non-obese untrained men. The participants were pair-matched based on their initial fat mass and then randomly allocated into one of two treatment groups: Full body (FB, n = 20), in which all muscle groups were trained in every session, or Split body (SB, n = 15), in which upper and lower muscle groups were trained alternated per session; both groups trained in non-consecutive days, three times per week with total number of sets performed equated between groups. Energy intake, body composition, and strength performance were evaluated at pre-training, and after 8-weeks of RT, as well as self-reported hunger, fullness, and desire to eat, that were assessed at fasted and feed states pre- and post-intervention. FB and SB resistance training increased fat-free mass (FFM) (p < 0.001); and FB induced greater maximal strength improvement (p = 0.027). At fasted state self-reported hunger increased, and fullness decreased, while in feed state desire to eat something fatty increased in both groups. Carbohydrate intake (p = 0.011) decreased in both groups. In conclusion, FB and SB training increased orexigenic drive (increasing hunger and decreasing fullness), however, total energy intake and fat mass did not change after 8-weeks of RT in non-obese untrained men.Registered under Brazilian Registry of Clinical Trials no. RBR-3wkcvyw., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We aimed to compare the effects of beta-alanine on Traditional Resistance Training (TRAD) or Blood Flow Restriction Training (BFR)., Methods: 19 subjects were randomly allocated to a Placebo ( n = 10) or beta-alanine ( n = 9) group. Subjects from both groups were trained unilaterally (unilateral arm curl) for six weeks, and each arm was trained using a different paradigm (BFR or TRAD). One repetition maximum (1RM) test measurements were performed before and after the strength training program. Work output was accessed as the total weight lifted (repetitions × weight lifted × sets) for the entire strength training program., Results: 1RM or total weight lifted was not increased by beta-alanine supplementation. However, the TRAD-trained arm showed a significantly increased 1RM and total weight lifted compared to the BFR arm ( p < 0.05)., Conclusion: We conclude that in the short-term (6 weeks) and following the current experimental conditions, beta-alanine does not benefit BFR or TRAD in terms of total weight lifted (volume of training) or maximal strength (1RM).

This study aimed to compare the effects of an 8-week creatine (CR) or placebo (PL) supplementation on muscle strength, thickness, endurance, and body composition employing different training paradigms with blood flow restriction (BFR) vs. traditional resistance training (TRAD). Seventeen healthy males were randomized between the PL ( n  = 9) and CR ( n  = 8) groups. Participants were trained unilaterally utilizing a within-between subject bicep curl exercise where each arm was allocated to TRAD or BFR for 8 weeks. Muscular strength, thickness, endurance, and body composition were evaluated. Creatine supplementation promoted increases in muscle thickness in TRAD and BFR compared with their placebo counterparts, however, without a significant difference between treatments ( p  = 0.349). TRAD training increased maximum strength (1 repetition maximum (1RM)) compared with BFR after 8 weeks of training ( p  = 0.021). Repetitions to failure at 30% of 1RM were increased in the BFR-CR group compared with the TRAD-CR group ( p  = 0.004). Repetitions to failure at 70% 1RM were increased from weeks 0-4 ( p  < 0.05) and 4-8 ( p  < 0.05) in all groups. Creatine supplementation exerted a hypertrophic effect when utilized with TRAD and BFR paradigms and increased muscle performance at 30% 1RM when utilized in conjunction with BFR. Therefore, creatine supplementation seems to amplify muscle adaptation following a BFR program. Registered in the Brazilian Registry of Clinical Trials (ReBEC), under the registration number: RBR-3vh8zgj., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Abstract: Lauver, JD, Moran, A, Guilkey, JP, Johnson, KE, Zanchi, NE, and Rotarius, TR. Acute responses to cycling exercise with blood flow restriction during various intensities. J Strength Cond Res 36(12): 3366-3373, 2022-The purpose of this study was to investigate the acute physiological responses during cycling at various intensities with blood flow restriction (BFR). Subjects ( N = 9; V̇ o2 peak = 36.09 ± 5.80 ml·kg -1 ·min -1 ) performed 5 protocols: high-intensity (HIGH), control (CON-90), 90% of ventilatory threshold (VT) work rate with BFR (90-BFR), 70% of VT with BFR (70-BFR), and 30% V̇ o2 peak with BFR (30-BFR). Protocols consisted of five 2-minute work intervals interspersed with 1-minute recovery intervals. Blood flow restriction pressure was 80% of limb occlusion pressure. V̇ o2 , muscle excitation, tissue oxygen saturation (StO 2 ), discomfort, and level of perceived exertion (RPE) were assessed. Muscle excitation was higher during HIGH (302.9 ± 159.9 %BSL [baseline]) compared with 70-BFR (99.7 ± 76.4 %BSL) and 30-BFR (98.2 ± 70.5 %BSL). StO 2 was greater during 90-BFR (40.7 ± 12.5 ∆BSL), 70-BFR (34.4 ± 15.2 ∆BSL), and 30-BFR (31.9 ± 18.7 ∆BSL) compared with CON-90 (4.4 ± 11.5 ∆BSL). 90-BFR (39.6 ± 12.0 ∆BSL) resulted in a greater StO 2 -Avg compared with HIGH (20.5 ± 13.8 ∆BSL). Also, HIGH (23.68 ± 5.31 ml·kg -1 ·min -1 ) resulted in a greater V̇ o2 compared with 30-BFR (15.43 ± 3.19 ml·kg -1 ·min -1 ), 70-BFR (16.65 ± 3.26 ml·kg -1 ·min -1 ), and 90-BFR (18.28 ± 3.89 ml·kg -1 ·min -1 ); 90-BFR (intervals: 4 = 15.9 ± 2.3; intervals: 5 = 16.4 ± 2.5) resulted in a greater RPE compared with 30-BFR (intervals: 4 = 13.3 ± 1.4; intervals: 5 = 13.7 ± 1.7) during intervals 4 and 5. These results suggest that when adding BFR to various intensities of aerobic exercise, consideration should be given to peak work and VT to provide a balance between high local physiological stress and perceptual responses., (Copyright © 2022 National Strength and Conditioning Association.)

As a key mechanism to maintain cellular homeostasis under stress conditions, autophagy/mitophagy is related to the occurrence of metabolic disorders, neurodegenerative diseases, cancer, and other aging-related diseases, but the relevant signal pathways regulating autophagy have not been clarified. Mammalian sterile 20-like kinase 1 (MST1) is a central regulatory protein of many metabolic pathways involved in the pathophysiological processes of aging and aging-related diseases and has become a critical integrator affecting autophagic signaling. Recent studies show that MST1 not only suppresses autophagy through directly phosphorylating Beclin-1 and/or inhibiting the protein expression of silent information regulator 1 (SIRT1) in the cytoplasm, but also inhibits BCL2/adenovirus E1B protein-interacting protein 3 (BNIP3)-, FUN14 domain containing 1 (FUNDC1)-, and Parkin (Parkinson protein 2)-mediated mitophagy by interacting with factors such as Ras association domain family 1A (RASSF1A). Indeed, a common pharmacological strategy for anti-aging is to induce autophagy/mitophagy through MST1 inhibition. This article reviews the role and mechanism of MST1 in regulating autophagy during aging, to provide evidence for the development of drugs targeting MST1., (© 2022. The Author(s) under exclusive licence to University of Navarra.)

Objectives: The purpose of this study was to compare the effects of two acute doses of Capsiate (CAP; 6 vs. 12 mg) on upper body resistance exercise performance in trained men., Methods: Using a randomized, crossover and double-blind design, 20 resistance-trained males were supplemented with low-dose CAP (6 mg), high-dose CAP (12 mg) or placebo 45 minutes before exercise. Subjects performed 4 sets of bench press with repetitions to failure at 70% 1 repetition maximum (1RM) and 2 minutes of rest between each set. The ratings of perceived exertion (RPE) and blood lactate were analyzed at baseline and after exercise., Results: Total weight lifted was greater in the low CAP (2,454.6 ± 448.6 kg) compared to placebo (2,354.7 ± 458.6 kg, p = 0.039) and high CAP (2,309.3 ± 428.1 kg, p = 0.001). There was no significant difference between conditions for RPE ( p = 0.155) and blood lactate ( p = 0.434)., Conclusion: In summary, 6 mg CAP increased total weight lifted and repetitions to failure on bench press exercise in trained men, while 12 mg did not present any effect.

Abstract: Lima-Soares, F, Pessoa, KA, Torres Cabido, CE, Lauver, J, Cholewa, J, Rossi, FE, and Zanchi, NE. Determining the arterial occlusion pressure for blood flow restriction: Pulse oximeter as a new method compared with a handheld Doppler. J Strength Cond Res 36(4): 1120-1124, 2022-In laboratorial and clinical settings, the use of Doppler ultrasound equipment has been considered the gold standard method to determine arterial occlusion pressure (AOP). However, the use of Doppler equipment is inherently limited to the technical expertise needed to perform AOP measurements. To overcome the technical difficulties of the use of Doppler equipment use in the determination of AOP, a simpler and less subjective methodology would be helpful for blood flow restriction (BFR) practitioners. In this regard, portable pulse oximetry has been largely used in clinical practice for measuring systolic pressures, as well as loss or recovery of pulse, with results similar to those observed with the use of Doppler equipment. For such purposes, the AOP from young male and female subjects was evaluated after different body positions (standing, seated, and supine positions). Loss of capillary blood flow or AOP was readily determined by simple visual inspection for the pulse oximeter and loss of sound for the Doppler equipment. The results presented herein strongly suggest the use of the portable pulse oximetry equipment as reliable, when compared with the handheld Doppler (seated k = 0.962, standing k = 0.845, and supine k = 0.963 and seated rs = 0.980, standing rs = 0.958, and supine rs = 0.955). Because AOP measurement by pulse oximetry is relatively easier to perform and financially more accessible than handheld Doppler equipment, BFR practitioners may benefit from this new methodology to measure AOP, thus determining individualized restriction pressures., (Copyright © 2020 National Strength and Conditioning Association.)

Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Cholewa, Shang, Yang, Ding, Liu, Xia, Zanchi and Wang.)

Abstract: Conrado de Freitas, M, Ricci-Vitor, AL, de Oliveira, JVNS, Quizzini, GH, Vanderlei, LCM, Silva, BSA, Zanchi, NE, Cholewa, JM, Lira, FS, and Rossi, FE. Appetite is suppressed after full-body resistance exercise compared with split-body resistance exercise: the potential influence of lactate and autonomic modulation. J Strength Cond Res 35(9): 2532-2540, 2021-The purposes of this study were to investigate the effects of full- vs. split-body resistance training on appetite and leptin response and to verify the potential involvement of lactate and autonomic modulation during this response in trained men. Twelve recreationally resistance-trained men (age = 26.1 ± 5.5 years) performed 3 randomized trials in 3 conditions: upper body (UB), lower body (LB), and full body (FB). The subjective rating of hunger was obtained through a visual analog scale. Leptin and lactate concentration were evaluated at rest, immediately after exercise, and during recovery. Heart rate variability in the time and frequency domains was recorded at baseline and during recovery (until 60 minutes after exercise) to assess autonomic modulation. The FB condition induced lower subjective hunger ratings than the UB at Post-1 hour (p < 0.05) and a significant difference in the area under the curve between conditions (p = 0.028) with lower hunger sensation for FB in relation to UB (p = 0.041). The FB presented greater lactate concentration and induced slower heart rate variability recovery in relation to UB and LB conditions (p < 0.05), and heart rate variability remained lower until 60 minutes after exercise compared with rest only in the FB condition. There was a significant negative correlation between subjective hunger ratings and lactate concentration only for the FB condition (r = -0.72, p = 0.028). Full-body resistance exercise induced lower subjective hunger ratings after exercise in relation to UB resistance exercise. The FB also induced higher lactate production and slower recovery of autonomic modulation compared with the UB and LB conditions. Future research is necessary to investigate a mechanistic relationship between lactate concentrations and hunger suppression after resistance exercise., (Copyright © 2019 National Strength and Conditioning Association.)

Background: Acute capsaicinoid and capsinoid supplementation has endurance and resistance exercise benefits; however, if these short-term performance benefits translate into chronic benefits when combined with resistance training is currently unknown. This study investigated changes of chronic Capsiate supplementation on muscular adaptations, inflammatory response and performance in untrained men., Methods: Twenty untrained men were randomized to ingest 12 mg Capsiate (CAP) or placebo in a parallel, double-blind design. Body composition and performance were measured at pre-training and after 6 weeks of resistance training. An acute resistance exercise session test was performed pre and post-intervention. Blood samples were collected at rest and post-resistance exercise to analyze Tumor necrosis factor- (TNF-), Soluble TNF- receptor (sTNF-r), Interleukin-6 (IL-6) and Interleukin-10 (IL-10)., Results: Exercise and CAP supplementation increased fat-free mass in comparison to baseline by 1.5 kg (P < 0.001), however, the majority of the increase (1.0 kg) resulted from an increase in total body water. The CAP change scores for fat-free mass were significantly greater in comparison to the placebo (CAP ∆%= 2.1 ± 1.8 %, PLA ∆%= 0.7 ± 1.3 %, P = 0.043) and there was a significant difference between groups in the bench press exercise (P = 0.034) with greater upper body strength change score for CAP (∆%= 13.4 ± 9.1 %) compared to placebo (∆%= 5.8 ± 5.2 %), P = 0.041. CAP had no effect on lower body strength and no supplementation interactions were observed for all cytokines in response to acute resistance exercise (P > 0.05)., Conclusion: Chronic Capsiate supplementation combined with resistance training during short period (6 weeks) increased fat-free mass and upper body strength but not inflammatory response and performance in young untrained men.

Abstract: Conrado de Freitas, M, Rossi, FE, Colognesi, LA, de Oliveira, JVNS, Zanchi, NE, Lira, FS, Cholewa, JM, and Gobbo, LA. Postactivation potentiation improves acute resistance exercise performance and muscular force in trained men. J Strength Cond Res 35(5): 1357-1363, 2021-The purpose of this study was to investigate the effects of heavy back squat (90% one repetition maximum [1RM]) postactivation potentiation (PAP) on acute resistance exercise performance and force production in recreationally trained men, and to verify the relationship between maximal strength and the PAP response. Ten resistance-trained men randomly completed 4 experimental trials: (a) back squats without PAP (No-PAP), (b) back squats with PAP, (c) maximum voluntary isometric contraction (MVIC) of the quadriceps without PAP, and (d) MVIC with PAP. Back squats were performed with 4 sets at 70% of 1 RM with 2 minutes of rest interval. The number of squats repetitions performed was recorded for each set, and a total number of repetitions were calculated to analyze performance. Maximum voluntary isometric contraction was measured using electronic dynamometer, and the peak force and mean force were recorded. Blood lactate concentration was analyzed presquat and postsquat exercise. Repetitions performed in the first set was significantly (p < 0.001) greater in the PAP condition (22.00 ± 5.14) compared with No-PAP (15.50 ± 5.10), which resulted in significantly (p = 0.001) more total repetitions performed in the PAP (56.20 ± 17.3) condition compared with No-PAP (48.80 ± 14.5). Maximum voluntary isometric contraction peak was higher in PAP than in No-PAP (PAP = 765.7 ± 147.8 vs. No-PAP = 696.8 ± 131.5 N, p = 0.006). No significant correlations were observed between back squat 1RM relative to body mass and the PAP response in squat and MVIC. There were no significant differences in lactate concentration between conditions. In conclusion, PAP resulting from a heavy load prior back squat exercise improved total volume during resistance exercise. In addition, PAP was effective to increase force production during MVIC, but there was no relationship between relative 1RM values and the PAP response in trained men., (Copyright © 2018 National Strength and Conditioning Association.)

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Cholewa, Shang, Yang, Ding, Wang, Su, Zanchi and Xia.)

Purpose: To screen for candidate hub genes associated with the effects of exercise on melanoma tumor tissues and to review the potential signaling pathways involved in this process using bioinformatics analysis., Methods: The GSE62628 expression profile was downloaded from Gene Expression Omnibus database. This data set contains 10 melanoma tumor tissues from two groups of exercise and nonexercise mice. The R software was utilized to identify differentially expressed genes between samples, and functional annotation and pathway analysis were performed. Results were visualized using Cytoscape software., Results: In total, 315 differentially expressed genes were obtained, including 294 upregulated and 21 downregulated genes. The functional analysis showed that these genes were mainly enriched in immune response, inflammatory response, and positive regulation of the ERK1/2 cascade in biological process functional groups. The top 10 candidate hub genes were C3, Kng1, C3ar1, Ptafr, Fgg, Alb, Pf4, Orm1, Aldh3b1, and Apob. The pathway analysis of the most significant module identified from the protein-protein interaction network revealed that the complement and coagulation cascades, Staphylococcus aureus infection, cytokine-cytokine receptor interaction, chemokine signaling pathway and phagosome were mainly involved. C3, C3ar1, Kng1, Ptafr, and Fgg may be the critical genes in the complement and coagulation cascades pathway, and S. aureus in the infection pathway., Conclusions: Exercise may ameliorate the immune response and inflammatory response in melanoma tissue, and further studies exploring their relationships are warranted.

Objectives: Performance in running-based sport depends on the ability to perform repetitive high intensity muscle contractions. Previous studies have shown that capsaicin analog (CAP) (i.e. Capsiate) supplementation may improve this performance. The purpose of this study was to investigate the acute effect of CAP supplementation on short (400 m) and middle distance (3000 m) running time-trial performance, maximum heart rate (HR), and rate of perceived exertion (RPE)., Methods: Twelve physically active men completed four randomized, double-blind trials: CAP condition (12 mg) or a placebo condition. Forty-five minutes after supplementation, the participants performed a 400- or 3000-meter running time trial. Time (in seconds) was recorded. HR was analyzed at rest and immediately post-exercise, and RPE was collected immediately after exercise., Results: For both the 400 m time-trial (CAP = 66.4 + 4.2 sec vs Placebo = 67.1 + 4.8 sec, p = 0.046) and the 3000 m time-trial (CAP = 893.9 ± 46.8 sec vs Placebo = 915.2 ± 67.6 sec, p = 0.015), the time in seconds was significantly less in the CAP compared to placebo conditions. There were no statistically significant differences for HR and RPE in any condition., Conclusion: In summary, acute CAP supplementation improved 400 m and 3000 m running time-trial performance in a distance-dependent way but without modifying the HR and RPE.

(1) Background: We investigated the effects of 28 days of beta-alanine (β-alanine) supplementation on the acute interference effect of high-intensity intermittent exercise (HIIE) on lower-body resistance exercise performance, body composition, and strength when combined with a resistance training program. (2) Methods: Twenty-two males were randomized into: β-alanine supplementation (6.4 g/day) or placebo (6.4 g/day maltodextrin) during 28 days. Total body water, intracellular and extracellular water, fat-free mass (FFM), and fat mass were assessed using bioelectrical impedance. Participants performed 5000-m HIIE (1:1 effort and rest ratio) followed by resistance exercise (four sets of 80% at 45° leg press until muscular failure) at baseline and after 28 days. The resistance training program consisted of three sets of 10 to 12 RM with 90 s of rest, four days per week. (3) Results: For the post-HIIE leg press volume, higher values were observed post-training than pre-training, but no group x time interaction was observed. There was a non-significant trend for an interaction in the FFM change (β-alanine = 2.8% versus placebo = 1.0%, p = 0.072). (4) Conclusion: Twenty-eight days of β-alanine supplementation did not prevent acute strength loss during resistance exercise after high-intensity interval exercise, nor increase strength or hypertrophic adaptations associated with resistance training.

Increased blood flow via vasodilation, metabolite production, and venous pooling contribute to the hyperemia and cellular swelling experienced during resistance training. It has been suggested that these effects play a role in hypertrophic adaptations. Over the past 2 decades, sport supplement products have been marketed to promote exercise hyperemia and intracellular fluid storage, thereby enhancing hypertrophy via acute swelling of myocytes. The three main classes of supplements hypothesized to promote exercise-induced hyperemia include vasodilators, such as nitric oxide precursor supplements; anaerobic energy system ergogenic aids that increase metabolite production, such as β-alanine and creatine; and organic osmolytes, such as creatine and betaine. Previous studies indicated that these dietary supplements are able to improve muscle performance and thus enhance muscle hypertrophy; however, recent evidences also point to these three classes of supplements affecting "secondary" physiological determinants of muscle mass accretion such as vasodilation, metabolite accumulation, and muscle cellular swelling. Although we recognize that the literature is relatively scarce regarding these topics, a better comprehension and discussion of these determinants can lead to increased knowledge and might guide further research regarding the proposed mechanisms of action of the identified compounds. In this case, increased knowledge may contribute to the development of improved efficacy, new products, or direct new research to specifically investigate those secondary effects. The aim of this review was to bring into focus new perspectives associated with secondary physiological effects induced by supplementation and to determine their relevance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

It is commonly accepted that adequate carbohydrate availability is necessary for optimal endurance performance. However, for strength- and physique-based athletes, sports nutrition research and recommendations have focused on protein ingestion, with far less attention given to carbohydrates. Varying resistance exercise protocols, such as differences in intensity, volume, and intraset rest prescriptions between strength-training and physique-training goals elicit different metabolic responses, which may necessitate different carbohydrate needs. The results of several acute and chronic training studies suggest that although severe carbohydrate restriction may not impair strength adaptations during a resistance training program, consuming an adequate amount of carbohydrate in the days leading up to testing may enhance maximal strength and strength-endurance performance. Although several molecular studies demonstrate no additive increases in postexercise mammalian target of rapamycin 1 phosphorylation with carbohydrate and protein compared with protein ingestion alone, the effects of chronic resistance training with carbohydrate restriction on muscle hypertrophy are conflicting and require further research to determine a minimal carbohydrate threshold necessary to optimize muscle hypertrophy. This review summarizes the current knowledge regarding carbohydrate availability and resistance training outcomes and poses new research questions that will better help guide carbohydrate recommendations for strength and physique athletes. In addition, given that success in physique sports is based on subjective appearance, and not objective physical performance, we also review the effects of subchronic carbohydrate ingestion during contest preparation on aesthetic appearance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Doxorubicin (DOX) is a chemotherapy agent widely used in clinical practice, and it is very efficient in tumor suppression, but the use of DOX is limited by a strong association with the development of severe muscle atrophy and cardiotoxicity effects. Reversion or neutralization of the muscular atrophy can lead to a better prognosis. Recent studies have proposed that the negative effect of DOX on skeletal muscle is linked to its inhibition of AMP-activated protein kinase (AMPk), a key mediator of cellular metabolism. On the basis of this, our goal was to evaluate if aerobic exercise or metformin treatment, activators of AMPk, would be able to attenuate the deleterious effects on skeletal muscle induced by the DOX treatment. C57BL6 mice received either saline (control) or DOX (2.5 mg/kg body weight) intraperitoneally, twice a week. The animals on DOX were further divided into groups that received adjuvant treatment in the form of moderate aerobic physical exercise (DOX+T) or metformin gavage (300 mg/body weight/day). Body weight, metabolism, distance run, muscle fiber cross-sectional area (CSA), and protein synthesis and degradation were assessed. We demonstrated that aerobic training, but not metformin, associated with DOX increased the maximal aerobic capacity without changing muscle mass or fiber CSA, rescuing the muscle fatigue observed with DOX treatment alone. This improvement was associated with AMPk activation, thus surpassing the negative effects of DOX on muscle performance and bioenergetics. In conclusion, aerobic exercise increases AMPk activation and improved the skeletal muscle function, reducing the side effects of DOX., (© 2018 Wiley Periodicals, Inc.)

Blood flow restriction (BFR) combined with low-intensity strength training has been shown to increase skeletal muscle mass and strength in a variety of populations. BFR results in a robust metabolic stress which is hypothesized to induce muscle growth via increased recruitment of fast-twitch muscle fibers, a greater endocrine response, and/or enhancing the cellular swelling contribution to the hypertrophic process. Following exercise, neutrophils are the first immune cells to initiate the tissue remodeling process via several mechanisms including an increased production of cytokines and recruitment of monocytes/macrophages, which facilitate the phagocytosis of foreign particles, the differentiation of myoblasts, and the formation of new myotubes. Thus, the purpose of this review was to discuss the mechanisms through which metabolic stress and immune cell recruitment may induce skeletal muscle remodeling following BFR strength training.

The positive influence of animal-based protein supplementation during muscle-damaging exercise has been widely studied. However, the effects of plant-based proteins remain unclear and require further clarification. This study investigated the protective role of oat protein against exercise induced muscle damage (EIMD), subsequent inflammation, and loss of performance induced by downhill running. Subjects consumed either oat protein (25 g protein) or a placebo for 14 days prior to a downhill running test and then for 4 days thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL-6 concentrations and serum creatine kinase, myoglobin and C reactive protein contents. In addition, oat protein supplementation significantly inhibited limb edema following damaging exercise, and the adverse effects on muscle strength, knee-joint range of motion, and vertical jump performance were lessened. Furthermore, the administration of oat protein facilitated recovery from exhaustive downhill running in this study. These findings demonstrated that oat protein supplementation has the potential to alleviate the negative effects of eccentric exercise in untrained young males.

Previous research has demonstrated the positive effects of concurrent/combined aerobic and resistance exercise or leucine supplementation on skeletal muscle protein synthesis (MPS) and hypertrophy in aging organisms. However, the effects of a multimodal intervention which combines both aerobic and resistance exercise and leucine supplementation has not been fully elucidated. Eighteen month old and 2 month old C57BL/6 mice were assigned to aging control (AC, n = 8), aging and multimodal intervention (AMI, n = 8) and young control (YC, n = 8). Mice in the YC and AC groups were fed an alanine-rich diet (3.4%), and mice in the AMI group received an isonitrogenous leucine-supplemented (5%) diet in combination with combined aerobic (30 minutes swimming) and resistance exercise training (incremental jumping submersed in water with overload corresponding to 40%-50% body weight) for a total of 4 weeks. The gastrocnemius muscles were dissected for western blotting detection (signaling proteins involved in MPS) and the ex vivo determination of protein synthesis and protein content. The muscle strength of the hind limbs was measured pre-experiment and repeated once per week on Sunday for 4 weeks. Mice in the AC and AMI groups showed lower ex vivo protein synthesis, protein content, expression of signaling proteins involved in MPS, maximal grip strength but higher plasma cortisol compared with the YC group post intervention. When compared to AC mice, the multimodal treatment led to lower activity of Sestrin2, higher expression of PI3K III and the phosphorylation of mTOR, p70S6K and 4E-BP1, as well as higher plasma leucine, wet gastrocnemius muscle weight and muscle weight to body weight ratio. Furthermore, the multimodal intervention induced more pronounced anabolic response such as higher ex vivo protein synthesis rate, total protein content, and myofibrillar fractions in gastrocnemius muscle, and greater maximum grip strength. The present research shows that a multimodal intervention including combined both aerobic and resistance exercise training and 5% leucine supplementation has the potential to maintain skeletal muscle protein synthesis and attenuate losses in muscular strength during the aging process.

Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic (Pi) and ions of hydrogen (H + )] in muscle cells. Traditional exercise protocol ( i.e ., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species (ROS) production and cell swelling. Changes in acute exercise routines, such as intensity, volume and rest between sets, are determinants for the magnitude of metabolic stress, furthermore, different types of training, such as low-intensity resistance training plus blood flow restriction and high intensity interval training, could be used to maximize metabolic stress during exercise. Thus, the objective of this review is to describe practical applications that induce metabolic stress and the potential effects of metabolic stress to increase systemic hormonal release, hypoxia, ROS production, cell swelling and muscle adaptations., Competing Interests: Conflict-of-interest statement: None.

Sarcopenia is defined as the progressive loss of muscle mass with age, and poses a serious threat to the physiological and psychological health of the elderly population with consequential economic and social burdens. Chronic low-grade inflammation plays a central role in the development of sarcopenia such that it alters cellular protein metabolism to favor proteolysis over synthesis, and thereby accelerates muscular atrophy. The purpose of this review is to highlight how exercise and nutrition intervention strategies can attenuate or treat sarcopenia. Resistance exercise increases not only muscle mass but also muscle strength, while aerobic exercise is able to ameliorate the age-related metabolic disorders. Concurrent exercise training integrates the advantages of both aerobic and resistance exercise, and may exert a significant synergistic effect in the aging organism. Higher protein intakes rich in the amino acid leucine appear to restore skeletal muscle protein metabolism balance by rescuing protein synthesis in older adults. There is good reason to believe that a multimodal treatment, a combination of exercise and increased leucine consumption in the diet, can combat some of the muscle loss associated with aging. Future research is needed to consolidate these findings to humans, and to further clarify to what extent and by which mechanisms protein metabolism might be directly involved in sarcopenia pathogenesis and the multimodal treatment responses.

Dietary proteins/essential amino acids (EAAs) are nutrients with anabolic properties that may increase muscle mass or attenuate muscle loss during immobilization and aging via the stimulation of muscle protein synthesis (MPS). An EAA's anabolic threshold, capable to maximize the stimulation of MPS has been hypothesized, but during certain conditions associated with muscle loss, this anabolic threshold seems to increase which reduces the efficacy of dietary EAAs to stimulate MPS. Preliminary studies have demonstrated that acute ingestion of dietary proteins/EAA (with a sufficient amount of leucine) was capable to restore the postprandial MPS during bed rest, immobilization or aging; however, whether these improvements translate into chronic increases (or attenuates loss) of muscle mass is equivocal. For example, although free leucine supplementation acutely increases MPS and muscle mass in some chronic studies, other studies have reported no increases in muscle mass following chronic leucine supplementation. In contrast, chronically increasing leucine intake via the consumption of an overall increase in dietary protein appears to be the most effective dietary intervention toward increasing or attenuating lean mass during aging; however, more research investigating the optimal dose and timing of protein ingestion is necessary. Several studies have demonstrated that decreases in postprandial MPS as a result of increased circulating oxidative and inflammatory are more responsible than muscle protein breakdown for the decreases in muscle mass during disuse and health aging. Therefore, nutritional interventions that reduce oxidation or inflammation in conjunction with higher protein intakes that overcome the anabolic resistance may enhance the MPS response to feeding and either increase muscle mass or attenuate loss. In preliminary studies, antioxidant vitamins and amino acids with antioxidant or anti-inflammatory properties show potential to restore the anabolic response associated with protein ingestion. More research, however, is required to investigate if these nutrients translate to increases in MPS and, ultimately, increased lean mass in aging humans. The purpose of the present review is to discuss the role of protein/EAA intake to enhance postprandial MPS during conditions associated with muscle loss, and bring new perspectives and challenges associated nutritional interventions aimed to optimize the anabolic effects of dietary protein/EAAs ingestion.

The purpose of this study was to verify the influence of the short and moderate intervals of recovery in response to an acute bout of exhaustive strength exercise on performance, inflammatory, and metabolic responses in healthy adults. Eight healthy subjects (age = 24.6 ± 4.1 years) performed 2 randomized sequences: short = 70% of 1 repetition maximum (1RM) with 30 seconds of rest between sets; moderate = 70% of 1RM with 90 seconds of rest between sets. All sequences of exercises were performed over 4 sets until movement failure in the squat and bench press exercises, respectively. The total number of repetitions performed was recorded for each set of each exercise for all sequences. The percentages of fat mass and fat-free mass were estimated by dual-energy x-ray absorptiometry. Glucose, tumor necrosis factor-α, interleukin (IL)-6, IL-10, and nonester fatty acid were assessed, at baseline, immediately after exercise, after 15 and 30 minutes. When compared with the maximum number of repetitions and the total weight lifted, there was a statistically significant decrease after both intervals. The only statistically significant decreases over time occurred at the post-15 minutes assessment of the IL-6 and glucose when a moderate interval of recovery was performed. When comparing the alterations between the pools (the mean of the cluster of all periods in each variable), there was a statistically significant increase on the IL-6 and IL-10 when a moderate interval of recovery was performed again, however, not considering a statistical difference on the IL-10. Thus, we concluded that different interval of recovery in response to exhaustive strength exercise decreases performance but in only moderate intervals, it is associated with inflammatory and metabolic response.

Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1(®) mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis. The white gastrocnemius muscles were used for determination of muscle size and signaling proteins involved in protein synthesis and degradation. The results show that both 8 weeks of leucine supplementation and aerobic training elevated the activity of mTOR (mammalian target of rapamycin) and its downstream target p70S6K and 4E-BP1, inhibited the ubiquitin-proteasome system, and increased fiber cross-sectional area (CSA) in white gastrocnemius muscle. Moreover, leucine supplementation in combination with exercise demonstrated more significant effects, such as greater CSA, protein content and altered phosphorylation (suggestive of increased activity) of protein synthesis signaling proteins, in addition to lower expression of proteins involved in protein degradation compared to leucine or exercise alone. The current study shows moderate aerobic training combined with 5% leucine supplementation has the potential to increase muscle size in fast-twitch skeletal muscle during aging, potentially through increased protein synthesis and decreased protein breakdown.

Aim: The aim of the present study was to evaluate the effect of oral caffeine ingestion during repeated sets of resistance., Methods: Fourteen moderately resistance-trained men (20.9 ± 0.36 years and 77.62 ± 2.07 kg of body weight) ingested a dose of caffeine (5 mg.kg-1) or placebo prior to 3 sets of bench press and 3 sets of leg press exercises, respectively. The study used a double-blind, counterbalanced, crossover design. Repetitions completed and total weight lifted were recorded in each set. Readiness to invest in both physical (RTIPE) and mental (RTIME) effort were assessed prior each set, and rating of perceived exertion (RPE) was recorded after each set. Rest and peak heart rates were determined via telemetry., Results: Caffeine ingestion result in increased number of repetitions to failure in bench press (F[1,13]=6.16, P=0.027) and leg press (F[1,13]=9.33, P=0.009) compared to placebo. The sum of repetitions performed in the 3 sets was 11.60% higher in bench press (26.86 ± 1.74; caffeine: 30.00 ± 1.87; P=0.027) and 19.10% in leg press (placebo: 40.0 ± 4.22; caffeine: 47.64 ± 4.69; P=0.009). Also, RTIME was increased in the caffeine condition both in bench press (F[1,13]=7.02, P=0.02) and in leg press (F[1,13]=5.41, P=0.03). There were no differences in RPE, RTIPE and HR (P>0.05) across conditions., Conclusion: Acute caffeine ingestion can improve performance in repeated sets to failure and increase RTIME in resistance-trained men.

Resistance training is a potent stimulus to increase skeletal muscle mass. The muscle protein accretion process depends on a robust synergistic action between protein intake and overload. The intake of protein after resistance training increases plasma amino acids, which results in the activation of signaling molecules leading to increased muscle protein synthesis (MPS) and muscle hypertrophy. Although both essential and non-essential amino acids are necessary for hypertrophy, the intake of free L-leucine or high-leucine whole proteins has been specifically shown to increase the initiation of translation that is essential for elevated MPS. The literature supports the use of protein intake following resistance-training sessions to enhance MPS; however, less understood are the effects of different protein sources and timing protocols on MPS. The sum of the adaptions from each individual training session is essential to muscle hypertrophy, and thus highlights the importance of an optimal supplementation protocol. The aim of this review is to present recent findings reported in the literature and to discuss the practical application of these results. In that light, new speculations and questions will arise that may direct future investigations. The information and recommendations generated in this review should be of benefit to clinical dietitians as well as those engaged in sports., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Human muscle hypertrophy brought about by voluntary exercise in laboratorial conditions is the most common way to study resistance exercise training, especially because of its reliability, stimulus control and easy application to resistance training exercise sessions at fitness centers. However, because of the complexity of blood factors and organs involved, invasive data is difficult to obtain in human exercise training studies due to the integration of several organs, including adipose tissue, liver, brain and skeletal muscle. In contrast, studying skeletal muscle remodeling in animal models are easier to perform as the organs can be easily obtained after euthanasia; however, not all models of resistance training in animals displays a robust capacity to hypertrophy the desired muscle. Moreover, some models of resistance training rely on voluntary effort, which complicates the results observed when animal models are employed since voluntary capacity is something theoretically impossible to measure in rodents. With this information in mind, we will review the modalities used to simulate resistance training in animals in order to present to investigators the benefits and risks of different animal models capable to provoke skeletal muscle hypertrophy. Our second objective is to help investigators analyze and select the experimental resistance training model that best promotes the research question and desired endpoints., (© 2013 Wiley Periodicals, Inc.)

Betaine is a methyl derivative of glycine first isolated from sugar beets. Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver. The ergogenic and clinical effects of betaine have been investigated with doses ranging from 500 to 9,000 mg/day. Some studies using animal models and human subjects suggest that betaine supplementation could promote adiposity reductions and/or lean mass gains. Moreover, previous investigations report positive effects of betaine on sports performance in both endurance- and resistance-type exercise, despite some conflicting results. The mechanisms underlying these effects are poorly understood, but could involve the stimulation of lipolysis and inhibition of lipogenesis via gene expression and subsequent activity of lipolytic-/lipogenic-related proteins, stimulation of autocrine/endocrine IGF-1 release and insulin receptor signaling pathways, stimulation of growth hormone secretion, increased creatine synthesis, increases in protein synthesis via intracellular hyper-hydration, as well as exerting psychological effects such as attenuating sensations of fatigue. However, the exact mechanisms behind betaine action and the long-term effects of supplementation on humans remain to be elucidated. This review aims to describe evidence for the use of betaine as an ergogenic and esthetic aid, and discuss the potential mechanisms underlying these effects.

The purpose of the present study was to determine the effects of short-term supplementation with the free acid form of b-hydroxyb-methylbutyrate (HMB-FA) on indices of muscle damage, protein breakdown, recovery and hormone status following a high-volume resistance training session in trained athletes. A total of twenty resistance-trained males were recruited to participate in a high-volume resistance training session centred on full squats, bench presses and dead lifts. Subjects were randomly assigned to receive either 3 g/d of HMB-FA or a placebo. Immediately before the exercise session and 48 h post-exercise, serum creatine kinase (CK), urinary 3-methylhistadine (3-MH), testosterone, cortisol and perceived recovery status (PRS) scale measurements were taken. The results showed that CK increased to a greater extent in the placebo (329%) than in the HMB-FA group (104%) (P¼0·004, d ¼ 1·6). There was also a significant change for PRS, which decreased to a greater extent in the placebo (9·1 (SEM 0·4) to 4·6 (SEM 0·5)) than in the HMB-FA group (9·1 (SEM 0·3) to 6·3 (SEM 0·3)) (P¼0·005, d ¼ 20·48). Muscle protein breakdown, measured by 3-MH analysis, numerically decreased with HMB-FA supplementation and approached significance (P¼0·08, d ¼ 0·12). There were no acute changes in plasma total or free testosterone, cortisol or C-reactive protein. In conclusion, these results suggest that an HMB-FA supplement given to trained athletes before exercise can blunt increases in muscle damage and prevent declines in perceived readiness to train following a high-volume, muscle-damaging resistance-training session.

Branched-chain amino acids (BCAA) (especially leucine) have been shown to activate protein synthesis pathways, decrease proteolysis and increase insulin sensitivity. Furthermore, it appears that leucine can be used as a nutritional therapy to avoid sarcopenia and skeletal muscle atrophy due to immobilization or glucocorticoid treatment. However, it is of note that all of these conditions are related to insulin resistance to varying degrees and affect different tissues, particularly skeletal muscle. Additionally, evidence from recent studies demonstrate that a combination of protein containing high levels of leucine with nutrients containing saturated fatty acids or an excess of leucine are capable of inducing insulin resistance. From this discussion, a few major questions arise. First, what is the role of a combination of macronutrients in inducing insulin resistance? Second, in insulin resistance, does leucine supplementation follow the same path observed under healthy conditions? Finally, what are the dose-dependent outcome and the latency of leucine effect under such conditions? The present article discusses these questions based on data from the literature and experiments performed by our group., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Dexamethasone (DEXA) is a potent immunosupressant and anti-inflammatory agent whose main side effects are muscle atrophy and insulin resistance in skeletal muscles. In this context, leucine supplementation may represent a way to limit the DEXA side effects. In this study, we have investigated the effects of a low and a high dose of leucine supplementation (via a bolus) on glucose homeostasis, muscle mass and muscle strength in energy-restricted and DEXA-treated rats. Since the leucine response may also be linked to the administration of this amino acid, we performed a second set of experiments with leucine given in bolus (via gavage) versus leucine given via drinking water. Leucine supplementation was found to produce positive effects (e.g., reduced insulin levels) only when administrated in low dosage, both via the bolus or via drinking water. However, under DEXA treatment, leucine administration was found to significantly influence this response, since leucine supplementation via drinking water clearly induced a diabetic state, whereas the same effect was not observed when supplied via the gavage.

We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min(-1)·mg protein(-1)) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a "time-efficient" strategy inducing metabolic adaptation.

Objective: We aimed to evaluate the effects of resistance exercise (RE) and leucine (LEU) supplementation on dexamethasone (DEXA)-induced muscle atrophy and insulin resistance., Methods: Male Wistar rats were randomly divided into DEXA (DEX), DEXA + RE (DEX-RE), DEXA + LEU (DEX-LEU), and DEXA + RE + LEU (DEX-RE-LEU) groups. Each group received DEXA 5 mg · kg(-1) · d(-1) for 7 d from drinking water and were pair-fed to the DEX group; LEU-supplemented groups received 0.135 g · kg(-1) · d(-1) through gavage for 7 d; the RE protocol was based on three sessions of squat-type exercise composed by three sets of 10 repetitions at 70% of maximal voluntary strength capacity., Results: The plantaris mass was significantly greater in both trained groups compared with the non-trained groups. Muscle cross-sectional area and fiber areas did not differ between groups. Both trained groups displayed significant increases in the number of intermediated fibers (IIa/IIx), a decreased number of fast-twitch fibers (IIb), an increased ratio of the proteins phospho(Ser2448)/total mammalian target of rapamycin and phospho(Thr389)/total 70-kDa ribosomal protein S6 kinase, and a decreased ratio of phospho(Ser253)/total Forkhead box protein-3a. Plasma glucose was significantly increased in the DEX-LEU group compared with the DEX group and RE significantly decreased hyperglycemia. The DEX-LEU group displayed decreased glucose transporter-4 translocation compared with the DEX group and RE restored this response. LEU supplementation worsened insulin sensitivity and did not attenuate muscle wasting in rats treated with DEXA. Conversely, RE modulated glucose homeostasis and fiber type transition in the plantaris muscle., Conclusion: Resistance exercise but not LEU supplementation promoted fiber type transition and improved glucose homeostasis in DEXA-treated rats., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge.

This study aimed to develop an equipment and system of resistance exercise (RE), based on squat-type exercise for rodents, with control of training variables. We developed an operant conditioning system composed of sound, light and feeding devices that allowed optimized RE performance by the animal. With this system, it is not necessary to impose fasting or electric shock for the animal to perform the task proposed (muscle contraction). Furthermore, it is possible to perform muscle function tests in vivo within the context of the exercise proposed and control variables such as intensity, volume (sets and repetitions), and exercise session length, rest interval between sets and repetitions, and concentric strength. Based on the experiments conducted, we demonstrated that the model proposed is able to perform more specific control of other RE variables, especially rest interval between sets and repetitions, and encourages the animal to exercise through short-term energy restriction and "disturbing" stimulus that do not promote alterations in body weight. Therefore, despite experimental limitations, we believe that this RE apparatus is closer to the physiological context observed in humans.

Physical inactivity leads to the accumulation of visceral fat and, consequently, to the activation of a network of inflammatory pathways which may promote development of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. These conditions belong to the "diseasome of physical inactivity". In contrast, the protective effect of regular exercise against diseases associated with chronic inflammation may to some extent be ascribed to an anti-inflammatory effect. The so called "acute exercise threshold", the complex mixture of several variables involved in exercise, such as type, volume, frequency, and intensity range is capable of inducing positive physiological adaptations and has been specifically addressed in the recent literature. The major concern is related to the level of the threshold: "exercise training shifts from a therapeutic adaptive intervention to one with potential pathological consequences". Nonetheless, if the mechanical stimulus is too weak to disrupt cellular homeostasis, training adaptations will not occur. Answering these questions could present practical applications, especially during inflammatory diseases associated with detrimental muscle effects and could theoretically constitute a "new" therapeutic approach to treat/improve an inflammatory state. This paper aims to describe specific data from the literature regarding the effects of exercise on inflammatory diseases in order to promote a more sophisticated perspective on the anti-inflammatory effects of exercise.

Abstract quality of life. Since there is no currently effective and safe treatment available for skeletal muscle atrophy, the search for new alternatives is necessary. Resistance exercise (RE) seems to be an important tool in the treatment of disuse-induced skeletal muscle atrophy by promoting positive functional (strength and power) and structural (hypertrophy and phenotypic changes) adaptive responses. Human and animal studies using different types of resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and eccentric) have obtained results of great importance. However, since RE is a complex phenomenon, lack of strict control of its variables (volume, frequency, intensity, muscle action, rest intervals) limits the interpretation of the impact of the manipulation on skeletal muscle remodeling and function under disuse. The aim of this review is to critically describe the functional and morphological role of resistance exercise in disuse-induced skeletal muscle atrophy with emphasis on the principles of training.

Background: The purpose of this study was to evaluate the effect of exhaustive exercise on proteins associated with muscle damage and regeneration, including IL-2, IL-4 and MyoD, in extensor digitorum longus (EDL) and soleus muscles and mesenteric (MEAT) and retroperitoneal adipose tissues (RPAT)., Methods: Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6) or 6 (E6 group, n = 6) hours after the exhaustion protocol, which consisted of running on a treadmill at approximately 70% of VO(2max) for fifty minutes and then at an elevated rate that increased at one m/min every minute, until exhaustion., Results: The control group (C group, n = 6) was not subjected to exercise. IL-2 protein expression increased at E0 in the soleus and EDL; at E2, this cytokine returned to control levels in both tissues. In the soleus, IL-2 protein expression was lower than that in the control at E6. IL-4 protein levels increased in EDL at E6, but the opposite result was observed in the soleus. MyoD expression increased at E6 in EDL., Conclusion: Exhaustive exercise was unable to modify IL-2 and IL-4 levels in MEAT and RPAT. The results show that exhaustive exercise has different effects depending on which muscle is analysed.

Amino acids such as leucine and its metabolite α-ketoisocaproate (KIC), are returning to be the focus of studies, mainly because of their anti-catabolic properties, through inhibition of muscle proteolysis and enhancement of protein synthesis. It is clear that these effects may counteract catabolic conditions, as well as enhance skeletal muscle mass and strength in athletes. Moreover, beta-hydroxy-beta-methylbutyrate (HMB) has been shown to produce an important effect in reducing muscle damage induced by mechanical stimuli of skeletal muscle. This review aims to describe the general scientific evidence of KIC and HMB supplementation clinical relevance, as well as their effects (e.g., increases in skeletal muscle mass and/or strength), associated with resistance training or other sports. Moreover, the possible mechanisms of cell signaling regulation leading to increases and/or sparing (during catabolic conditions) of skeletal muscle mass are discussed in detail based on the recent literature.