Skeletal muscle fiber type and TMS-induced muscle relaxation in unfatigued and fatigued knee-extensor muscles.

The force drop after transcranial magnetic stimulation (TMS) delivered to the motor cortex during voluntary muscle contractions could inform about muscle relaxation properties. Because of the physiological relation between skeletal muscle fiber-type distribution and size and muscle relaxation, TMS could be a noninvasive index of muscle relaxation in humans. By combining a noninvasive technique to record muscle relaxation in vivo (TMS) with the gold standard technique for muscle tissue sampling (muscle biopsy), we investigated the relation between TMS-induced muscle relaxation in unfatigued and fatigued states, and muscle fiber-type distribution and size. Sixteen participants (7F/9M) volunteered to participate. Maximal knee-extensor voluntary isometric contractions were performed with TMS before and after a 2-min sustained maximal voluntary isometric contraction. Vastus lateralis muscle tissue was obtained separately from the participants' dominant limb. Fiber type I distribution and relative cross-sectional area of fiber type I correlated with TMS-induced muscle relaxation at baseline (r = 0.67, adjusted P = 0.01; r = 0.74, adjusted P = 0.004, respectively) and normalized TMS-induced muscle relaxation as a percentage of baseline (r = 0.50, adjusted P = 0.049; r = 0.56, adjusted P = 0.031, respectively). The variance in the normalized peak relaxation rate at baseline (59.8%, P < 0.001) and in the fatigue resistance (23.0%, P = 0.035) were explained by the relative cross-sectional area of fiber type I to total fiber area. Fiber type I proportional area influences TMS-induced muscle relaxation, suggesting TMS as an alternative method to noninvasively inform about skeletal muscle relaxation properties.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. We showed that fiber type I proportional area influences the TMS-induced muscle relaxation, suggesting that TMS could be used for the noninvasive estimation of muscle relaxation in unfatigued and fatigued human muscles when the feasibility of more direct method to study relaxation properties (i.e., muscle biopsy) is restricted.

Keep calm and keep rowing: the psychophysical effects of dragon boat program in breast cancer survivors.

PURPOSE: Dragon Boat discipline has become a popular type of physical exercise among women with breast cancer. The present study aims to investigate the effects of Dragon Boat activity on body composition, physical function, and psychosocial aspects (i.e., body appreciation and quality of life [QoL]) in women operated for breast cancer. METHODS: Thirty-one women (age, 57.88 ± 7.88 years; BMI, 27.86 ± 6.38 kg·m-2) with a previous breast removal surgery were recruited and randomized into two groups: Dragon Boat group (DB, N = 18) or a home-based non-supervised training program (home exercise group; HG, N = 13). All participants underwent body composition, handgrip test, 30-s chair stand test (30CST), 6-min walking test (6MWT), and shoulder mobility measurements at baseline and after 12 weeks of intervention. Participants also filled out the Body Appreciation Scale-2 (BAS-2) and the Short Form Health Survey-12 (SF-12) self-report questionnaires. RESULTS: Dragon Boat activity significantly improved the 30CST (+ 6%, p = .011) and 6MWT performance (+ 30%, p = .011) compared to a home-based non-supervised training program. Moreover, 20% (3/15 women) of women in the DB group obtained a reliable change from pre- to post-intervention in the BAS-2 and in the mental QoL component of the SF-12 (vs 15% and 0% of the HC group). No reliable change emerged for the physical component of the SF-12. CONCLUSION: Dragon Boat activity is efficient to improve lower limb strength in women operated for breast cancer. Furthermore, Dragon Boat activity emerged to improve body appreciation and mental QoL in some of the women assigned to this activity. Importantly, no adverse events were documented during the intervention. TRIAL REGISTRATION: NCT05206526 (10/02/2022).

Alterations in magnitude and spatial distribution of erector spinae muscle activity in cyclists with a recent history of low back pain.

PURPOSE: While cycling offers several health benefits, repetitive loading and maintenance of static postures for prolonged periods expose cyclists to low back pain (LBP). Despite high LBP prevalence in cyclists, underlying pathomechanics and specific lumbar region muscle activation patterns during cycling are unclear. Here, we compared lumbar erector spinae (ES) muscles activation and spatial distribution activity in cyclists with and without recent LBP history. METHODS: Ten cyclists with recent LBP history (LBPG; Oswestry Disability Index score ~ 17.8%) and 11 healthy cyclists (CG) were recruited. After assessing the Functional Threshold Power (FTP), participants underwent an incremental cycling test with 4 × 3 min steps at 70%, 80%, 90%, and 100% of their FTP. High-density surface electromyography (HDsEMG) signals were recorded from both lumbar ES using two 64-channel grids. Information about ES activation levels (root-mean-square, RMS), degree of homogeneity (entropy), and cranio-caudal displacement of muscle activity (Y-axis coordinate of the barycenter of RMS maps) was extracted from each grid separately and then grand-averaged across both grids. RESULTS: Repeated-measure 2-way ANOVAs showed a significant intensity by group interaction for RMS amplitude (p = 0.003), entropy (p = 0.038), and Y-bar displacement (p = 0.033). LBPG increased RMS amplitude between 70-100% (+ 19%, p = 0.010) and 80-100% FTP (+ 21%, p = 0.004) and decreased entropy between 70-100% FTP (- 8.4%, p = 0.003) and 80-100% FTP (- 8.5%, p = 0.002). Between-group differences emerged only at 100% FTP (+ 9.6%, p = 0.049) for RMS amplitude. CONCLUSION: Our findings suggest that cyclists with recent LBP history exhibit higher ES muscles activation and less homogeneous activity compared to healthy controls, suggesting potential inefficient muscle recruitment strategy. TRIAL REGISTRATION NUMBER: HEC-DSB/09-2023.

Non-invasive estimation of muscle fibre size from high-density electromyography.

Because of the biophysical relation between muscle fibre diameter and the propagation velocity of action potentials along the muscle fibres, motor unit conduction velocity could be a non-invasive index of muscle fibre size in humans. However, the relation between motor unit conduction velocity and fibre size has been only assessed indirectly in animal models and in human patients with invasive intramuscular EMG recordings, or it has been mathematically derived from computer simulations. By combining advanced non-invasive techniques to record motor unit activity in vivo, i.e. high-density surface EMG, with the gold standard technique for muscle tissue sampling, i.e. muscle biopsy, here we investigated the relation between the conduction velocity of populations of motor units identified from the biceps brachii muscle, and muscle fibre diameter. We demonstrate the possibility of predicting muscle fibre diameter (R2  = 0.66) and cross-sectional area (R2  = 0.65) from conduction velocity estimates with low systematic bias (∼2% and ∼4% respectively) and a relatively low margin of individual error (∼8% and ∼16%, respectively). The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling. The non-invasive nature of high-density surface EMG for the assessment of muscle fibre size may be useful in studies monitoring child development, ageing, space and exercise physiology, although the applicability and validity of the proposed methodology need to be more directly assessed in these specific populations by future studies. KEY POINTS: Because of the biophysical relation between muscle fibre size and the propagation velocity of action potentials along the sarcolemma, motor unit conduction velocity could represent a potential non-invasive candidate for estimating muscle fibre size in vivo. This relation has been previously assessed in animal models and humans with invasive techniques, or it has been mathematically derived from simulations. By combining high-density surface EMG with muscle biopsy, here we explored the relation between the conduction velocity of populations of motor units and muscle fibre size in healthy individuals. Our results confirmed that motor unit conduction velocity can be considered as a novel biomarker of fibre size, which can be adopted to predict muscle fibre diameter and cross-sectional area with low systematic bias and margin of individual error. The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling.

Postabsorptive muscle protein synthesis is higher in outpatients as compared to inpatients.

Several factors affect muscle protein synthesis (MPS) in the postabsorptive state. Extreme physical inactivity (e.g., bedrest) may reduce basal MPS, whereas walking may augment basal MPS. We hypothesized that outpatients would have a higher postabsorptive MPS than inpatients. To test this hypothesis, we conducted a retrospective analysis. We compared 152 outpatient participants who arrived at the research site the morning of the MPS assessment with 350 Inpatient participants who had an overnight stay in the hospital unit before the MPS assessment the following morning. We used stable isotopic methods and collected vastus lateralis biopsies ∼2 to 3 h apart to assess mixed MPS. MPS was ∼12% higher (P < 0.05) for outpatients than inpatients. Within a subset of participants, we discovered that after instruction to limit activity, outpatients (n = 13) took 800 to 900 steps in the morning to arrive at the unit, seven times more steps than inpatients (n = 12). We concluded that an overnight stay in the hospital as an inpatient is characterized by reduced morning activity and causes a slight but significant reduction in MPS compared with participants studied as outpatients. Researchers should be aware of physical activity status when designing and interpreting MPS results.NEW & NOTEWORTHY The postabsorptive muscle protein synthesis rate is lower in the morning after an overnight inpatient hospital stay compared with an outpatient visit. Although only a minimal amount of steps was conducted by outpatients (∼900), this was enough to increase postabsorptive muscle protein synthesis rate.

Characterization of the need for galactofuranose during the Neurospora crassa life cycle.

Galactofuranose is a constituent of the cell walls of filamentous fungi. The galactofuranose can be found as a component of N-linked oligosaccharides, in O-linked oligosaccharides, in GPI-anchored galactomannan, and in free galactomannan. The Neurospora genome contains a single UDP-galactose mutase gene (ugm-1/NCU01824) and two UDP-galactofuranose translocases used to import UDP-galactofuranose into the lumen of the Golgi apparatus (ugt-1/NCU01826 and ugt-2/NCU01456). Our results demonstrate that loss of galactofuranose synthesis or its translocation into the lumen of the secretory pathway affects the morphology and growth rate of the vegetative hyphae, the production of conidia (asexual spores), and dramatically affects the sexual stages of the life cycle. In mutants that are unable to make galactofuranose or transport it into the lumen of the Golgi apparatus, ascospore development is aborted soon after fertilization and perithecium maturation is aborted prior to the formation of the neck and ostiole. The Neurospora genome contains three genes encoding possible galactofuranosyltransferases from the GT31 family of glycosyltransferases (gfs-1/NCU05878, gfs-2/NCU07762, and gfs-3/NCU02213) which might be involved in generating galactofuranose-containing oligosaccharide structures. Analysis of triple KO mutants in GT31 glycosyltransferases shows that these mutants have normal morphology, suggesting that these genes do not encode vital galactofuranosyltransferases.

Athletic bioimpedance-based equations underestimate fat free mass components in male elite soccer players: development and validation of new soccer-specific predictive models.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a rapid and user-friendly technique for assessing body composition in sports. Currently, no sport-specific predictive equations are available, and the utilization of generalized formulas can introduce systematic bias. The objectives of this study were as follows: (i) to develop and validate new predictive models for estimating fat-free mass (FFM) components in male elite soccer players; (ii) to evaluate the accuracy of existing predictive equations. METHODS: A total of 102 male elite soccer players (mean age 24.7 ± 5.7 years), participating in the Italian first league, underwent assessments during the first half of the in-season period and were randomly divided into development and validation groups. Bioelectrical resistance (R) and reactance (Xc), representing the bioimpedance components, were measured using a foot-to-hand BIA device at a single frequency of 50 kHz. Dual-energy X-ray absorptiometry was employed to acquire reference data for FFM, lean soft tissue (LST), and appendicular lean soft tissue (ALST). The validation of the newly developed predictive equations was conducted through regression analysis, Bland-Altman tests, and the area under the curves (AUC) of regression receiver operating characteristic (RROC) curves. RESULTS: Developed models were: FFM = - 7.729 + (body mass × 0.686) + (stature2/R × 0.227) + (Xc × 0.086) + (age × 0.058), R2 = 0.97, Standard error of estimation (SEE) = 1.0 kg; LST = - 8.929 + (body mass × 0.635) + (stature2/R × 0.244) + (Xc × 0.093) + (age × 0.048), R2 = 0.96, SEE = 0.9 kg; ALST = - 24.068 + (body mass × 0.347) + (stature2/R × 0.308) + (Xc × 0.152), R2 = 0.88, SEE = 1.4 kg. Train-test validation, performed on the validation group, revealed that generalized formulas for athletes underestimated all the predicted FFM components (p < 0.01), while the new predictive models showed no mean bias (p > 0.05), with R2 values ranging from 0.83 to 0.91, and no trend (p > 0.05). The AUC scores of the RROC curves indicated an accuracy of 0.92, 0.92, and 0.74 for FFM, LST, and ALST, respectively. CONCLUSIONS: The utilization of generalized predictive equations leads to an underestimation of FFM and ALST in elite soccer players. The newly developed soccer-specific formulas enable valid estimations of body composition while preserving the portability of a field-based method.

Effect of resistance training on bioelectrical phase angle in older adults: a systematic review with Meta-analysis of randomized controlled trials.

Resistance training has been proposed as a valid practice to counteract the aging effect on body mass and its components, which can be easily evaluated though the bioelectrical impedance analysis. This study aimed to achieve a systematic review with meta-analysis on the impact of resistance training on bioelectrical proprieties in older adults.A literature review was done in four electronic databases up to 1 January 2022. The inclusion criteria were: (i) participants aged ≥ 60 years; (ii) resistance training lasted ≥ 8 weeks; (iii) measurement of raw bioelectrical parameters in randomized controlled study designs.The outcomes of the trial had to be bioelectrical phase angle (PhA), resistance (R), and reactance (Xc). The methodological quality was assessed using the Rosendal scale.Overall, seven studies with a total of 344 participants were eligible for the analysis. The quality assessment yielded a score of 71.3%. Bioelectrical PhA (0.52 degree [95%CI 0.32, 0.71], p < 0.001) and Xc (3.58 ohms [95%CI 1.97, 5.19], p < 0.001) increased, whereas R decreased (-28.50 ohms [95%CI -41.39, -15.60], p < 0.001) after the resistance training programs.In this meta-analysis, resistance training promoted increases of PhA, which result from an increase in Xc concomitant with a reduction in R. According to the bioimpedance vector analysis, resistance-trained people experienced a beneficial leftward vector displacement, whilst inactivity induced a rightward vector displacement within the R-Xc graph. In future, more sophisticated and rigorous studies that address specific criteria, methods and targeted designs are required to identify which equipment and protocols allow for an optimization of the resistance training effects.Registration code in PROSPERO: CRD42020168057.

Skeletal Muscle Bioenergetics in Critical Limb Ischemia and Diabetes.

INTRODUCTION: Mitochondrial dysfunction is implicated in the metabolic myopathy accompanying peripheral artery disease (PAD) and critical limb ischemia (CLI). Type-2 diabetes mellitus (T2DM) is a major risk factor for PAD development and progression to CLI and may also independently be related to mitochondrial dysfunction. We set out to determine the effect of T2DM in the relationship between CLI and muscle mitochondrial respiratory capacity and coupling control. METHODS: We studied CLI patients undergoing revascularization procedures or amputation, and non-CLI patients with or without T2DM of similar age. Mitochondrial respiratory capacity and function were determined in lower limb permeabilized myofibers by high-resolution respirometry. RESULTS: Fourteen CLI patients (65 ± 10y) were stratified into CLI patients with (n = 8) or without (n = 6) T2DM and were compared to non-CLI patients with (n = 18; 69 ± 5y) or without (n = 19; 71 ± 6y) T2DM. Presence of CLI but not T2DM had a marked impact on all mitochondrial respiratory states in skeletal muscle, adjusted for the effects of sex. Leak respiration (State 2, P < 0.025 and State 4o, P < 0.01), phosphorylating respiration (P < 0.001), and maximal respiration in the uncoupled state (P < 0.001), were all suppressed in CLI patients, independent of T2DM. T2DM had no significant effect on mitochondrial respiratory capacity and function in adults without CLI. CONCLUSIONS: Skeletal muscle mitochondrial respiratory capacity was blunted by ∼35% in patients with CLI. T2DM was not associated with muscle oxidative capacity and did not moderate the relationship between muscle mitochondrial respiratory capacity and CLI.

Ketogenic diets, physical activity and body composition: a review.

Obesity remains a serious relevant public health concern throughout the world despite related countermeasures being well understood (i.e. mainly physical activity and an adjusted diet). Among different nutritional approaches, there is a growing interest in ketogenic diets (KD) to manipulate body mass (BM) and to enhance fat mass loss. KD reduce the daily amount of carbohydrate intake drastically. This results in increased fatty acid utilisation, leading to an increase in blood ketone bodies (acetoacetate, 3-ß-hydroxybutyrate and acetone) and therefore metabolic ketosis. For many years, nutritional intervention studies have focused on reducing dietary fat with little or conflicting positive results over the long term. Moreover, current nutritional guidelines for athletes propose carbohydrate-based diets to augment muscular adaptations. This review discusses the physiological basis of KD and their effects on BM reduction and body composition improvements in sedentary individuals combined with different types of exercise (resistance training or endurance training) in individuals with obesity and athletes. Ultimately, we discuss the strengths and the weaknesses of these nutritional interventions together with precautionary measures that should be observed in both individuals with obesity and athletic populations. A literature search from 1921 to April 2021 using Medline, Google Scholar, PubMed, Web of Science, Scopus and Sportdiscus Databases was used to identify relevant studies. In summary, based on the current evidence, KD are an efficient method to reduce BM and body fat in both individuals with obesity and athletes. However, these positive impacts are mainly because of the appetite suppressive effects of KD, which can decrease daily energy intake. Therefore, KD do not have any superior benefits to non-KD in BM and body fat loss in individuals with obesity and athletic populations in an isoenergetic situation. In sedentary individuals with obesity, it seems that fat-free mass (FFM) changes appear to be as great, if not greater, than decreases following a low-fat diet. In terms of lean mass, it seems that following a KD can cause FFM loss in resistance-trained individuals. In contrast, the FFM-preserving effects of KD are more efficient in endurance-trained compared with resistance-trained individuals.

The effect of resistance training programs on lean body mass in postmenopausal and elderly women: a meta-analysis of observational studies.

Aging and menopause are associated with morphological and functional changes which may lead to loss of muscle mass and therefore quality of life. Resistance training (RT) is an effective training mode to increase muscle mass. We reviewed the existing literature to identify studies implementing RT protocols and evaluating muscle hypertrophy exclusively in healthy, postmenopausal and elderly women. Participants' age range was comprised between 50 and 80 years. The primary outcome observed was muscle hypertrophy. Fat mass was also evaluated, if available. PubMed and Web of Science were the screened database, and original articles written in English and published from 2000 up to 2020 were included. 26 articles were considered eligible and included. Quality assessment revealed a "moderate quality" of the included studies, however the majority of studies was able to reach level 4 of evidence and on overall grade of recommendation C. In total, data from 745 female participants subjected to different forms of resistance training were considered. Heterogeneity across studies was present regarding study design, intervention length (mean 16 weeks), training frequency (3 d/w), no. of exercises (n = 7.4) and participants' age (65.8 ± 4.9 years). Small-to-moderate significant increases (k = 43; SMD = 0.44; 95% CI 0.28; 0.60; p < 0.0001) of lean body mass were observed in post-menopausal and elderly women, regardless of age, intervention period, weekly training frequency and no. of exercises. No effects were noted for fat mass (k = 17; SMD = 0.27; 95% CI - 0.02; 0.55; p = 0.07). Studies need to concentrate on providing information regarding training parameters to more effectively counteract the effects of aging and menopause on skeletal muscle mass.

Skeletal muscle-specific knockout of DEP domain containing 5 protein increases mTORC1 signaling, muscle cell hypertrophy, and mitochondrial respiration.

mTORC1 regulates protein synthesis and in turn is regulated by growth factors, energy status, and amino acid availability. In kidney cell (HEK293-T) culture, the GAP activity toward RAG (GATOR1) protein complex suppresses activation of the RAG A/B-RAG C/D heterodimer when amino acids are insufficient. During amino acid sufficiency, the RAG heterodimer recruits mTORC1 to the lysosomal membrane where its interaction with Ras homolog enriched in brain (Rheb) stimulates mTORC1's kinase activity. The DEP domain containing 5 (DEPDC5) protein, a GATOR1 subunit, causes familial focal epilepsy when mutated, and global knockout of the Depdc5 gene is embryonically lethal. To study the function of DEPDC5 in skeletal muscle, we generated a muscle-specific inducible Depdc5 knockout mouse, hypothesizing that knocking out Depdc5 in muscle would make mTORC1 constitutively active, causing hypertrophy and improving muscle function. Examining mTORC1 signaling, morphology, mitochondrial respiratory capacity, contractile function, and applied physical function (e.g. rotarod, treadmill, grip test, and wheel running), we observed that mTORC1 activity was significantly higher in knockout (KO) mice, indicated by the increased phosphorylation of mTOR and its downstream effectors (by 118% for p-mTOR/mTOR, 114% for p-S6K1/S6K1, and 35% for p-4E-BP1/4E-BP1). The KO animals also exhibited soleus muscle cell hypertrophy and a 2.5-fold increase in mitochondrial respiratory capacity. However, contrary to our hypothesis, neither physical nor contractile function improved. In conclusion, DEPDC5 depletion in adult skeletal muscle removes GATOR1 inhibition of mTORC1, resulting in muscle hypertrophy and increased mitochondrial respiration, but does not improve overall muscle quality and function.

The Importance of Resistance Exercise Training to Combat Neuromuscular Aging.

Older adults undergoing age-related decrements in muscle health can benefit substantially from resistance exercise training, a potent stimulus for whole muscle and myofiber hypertrophy, neuromuscular performance gains, and improved functional mobility. With the use of advancing technologies, research continues to elucidate the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription. This review highlights the current knowledge in these areas and emphasizes knowledge gaps that require future attention of the field.

Whey Protein Hydrolysate Increases Amino Acid Uptake, mTORC1 Signaling, and Protein Synthesis in Skeletal Muscle of Healthy Young Men in a Randomized Crossover Trial.

BACKGROUND: Muscle protein synthesis (MPS) can be stimulated by ingestion of protein sources, such as whey, casein, or soy. Protein supplementation can enhance muscle protein synthesis after exercise and may preserve skeletal muscle mass and function in aging adults. Therefore, identifying protein sources with higher anabolic potency is of high significance. OBJECTIVE: The aim of this study was to determine the anabolic potency and efficacy of a novel whey protein hydrolysate mixture (WPH) on mechanistic target of rapamycin complex 1 (mTORC1) signaling and skeletal MPS in healthy young subjects. METHODS: Ten young men (aged 28.7 ± 3.6 y, 25.2 ± 2.9 kg/m2 body mass index [BMI]) were recruited into a double-blind two-way crossover trial. Subjects were randomized to receive either 0.08 g/kg of body weight (BW) of WPH or an intact whey protein (WHEY) mixture during stable isotope infusion experiments. Fractional synthetic rate, leucine and phenylalanine kinetics, and markers of amino acid sensing were assessed as primary outcomes before and 1-3 h after protein ingestion using a repeated measures mixed model. RESULTS: Blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle and intracellular muscle leucine concentration significantly increased to a similar extent 1 h after ingestion of both mixtures (P < 0.05). Phosphorylation of S6K1 (i.e. a marker of mTORC1 activation) increased equally by ∼20% 1-h postingestion (P < 0.05). Ingestion of WPH and WHEY increased mixed MPS similarly in both groups by ∼43% (P < 0.05); however, phenylalanine utilization for synthesis increased in both treatments 1-h postingestion but remained elevated 3-h postingestion only in the WPH group (P < 0.05). CONCLUSIONS: We conclude that a small dose of WPH effectively increases leucine transport into muscle, activating mTORC1 and stimulating MPS in young men. WPH anabolic potency and efficacy for promoting overall muscle protein anabolism is similar to WHEY, an intact protein source. This trial was registered at clinicaltrials.gov as NCT03313830.

Muscle Protein Anabolic Resistance to Essential Amino Acids Does Not Occur in Healthy Older Adults Before or After Resistance Exercise Training.

Background: The muscle protein anabolic response to contraction and feeding may be blunted in older adults. Acute bouts of exercise can improve the ability of amino acids to stimulate muscle protein synthesis (MPS) by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling, but it is not known whether exercise training may improve muscle sensitivity to amino acid availability. Objective: The aim of this study was to determine if muscle protein anabolism is resistant to essential amino acids (EAAs) and whether resistance exercise training (RET) improves muscle sensitivity to EAA in healthy older adults. Methods: In a longitudinal study, 19 healthy older adults [mean ± SD age: 71 ± 4 y body mass index (kg/m2): 28 ± 3] were trained for 12 wk with a whole-body program of progressive RET (60-75% 1-repetition maximum). Body composition, strength, and metabolic health were measured pre- and posttraining. We also performed stable isotope infusion experiments with muscle biopsies pre- and posttraining to measure MPS and markers of amino acid sensing in the basal state and in response to 6.8 g of EAA ingestion. Results: RET increased muscle strength by 16%, lean mass by 2%, and muscle cross-sectional area by 27% in healthy older adults (P < 0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of protein kinase B, 4E binding protein 1, 70-kDa S6 protein kinase, and ribosomal protein S6) increased after EAA ingestion (P < 0.05) pre- and posttraining. RET increased basal MPS by 36% (P < 0.05); however, RET did not affect the response of MPS and mTORC1 signaling to EAA ingestion. Conclusion: RET increases strength and basal MPS, promoting hypertrophy in healthy older adults. In these subjects, a small dose of EAAs stimulates muscle mTORC1 signaling and MPS, and this response to EAAs does not improve after RET. Our data indicate that anabolic resistance to amino acids may not be a problem in healthy older adults. This trial was registered at www.clinicaltrials.gov as NCT02999802.

Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males.

BACKGROUND: Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males. METHODS: Thirty-four resistance-trained males were randomly assigned to time-restricted feeding (TRF) or normal diet group (ND). TRF subjects consumed 100 % of their energy needs in an 8-h period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. The remaining 16 h per 24-h period made up the fasting period. Subjects in the ND group consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. Groups were matched for kilocalories consumed and macronutrient distribution (TRF 2826 ± 412.3 kcal/day, carbohydrates 53.2 ± 1.4 %, fat 24.7 ± 3.1 %, protein 22.1 ± 2.6 %, ND 3007 ± 444.7 kcal/day, carbohydrates 54.7 ± 2.2 %, fat 23.9 ± 3.5 %, protein 21.4 ± 1.8). Subjects were tested before and after 8 weeks of the assigned diet and standardized resistance training program. Fat mass and fat-free mass were assessed by dual-energy x-ray absorptiometry and muscle area of the thigh and arm were measured using an anthropometric system. Total and free testosterone, insulin-like growth factor 1, blood glucose, insulin, adiponectin, leptin, triiodothyronine, thyroid stimulating hormone, interleukin-6, interleukin-1ß, tumor necrosis factor α, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. Bench press and leg press maximal strength, resting energy expenditure, and respiratory ratio were also tested. RESULTS: After 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group. CONCLUSIONS: Our results suggest that an intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males.

Effects of n-3 polyunsaturated fatty acids (ω-3) supplementation on some cardiovascular risk factors with a ketogenic Mediterranean diet.

BACKGROUND: the ketogenic diet (KD) has become a widely used nutritional approach for weight loss. Some of the KD's positive effects on metabolism and cardiovascular risk factors are similar to those seen after n-3 polyunsaturated fatty acids (ω-3) supplementation. We hypothesized that a ketogenic Mediterranean diet with phytoextracts combined with ω-3 supplementation may have increased positive effects on cardiovascular risk factors and inflammation. METHODS: We analyzed 34 male overweight subjects; aged between 25 and 65 years who were overall healthy apart from overweight. The subjects followed a ketogenic diet protocol for four weeks; with (KDO3) or without (KD) ω-3 supplementation. RESULTS: All subjects experienced a significant loss of body weight and body fat and there was no significant differences between treatment (body weight: KD-4.7 kg, KDO3-4.03 kg, body fat KD-5.41 kg, KDO3-5.86 kg). There were also significant decreases in total cholesterol, LDL-c, and glucose levels. Triglycerides and insulin levels decreased more in KDO3 vs. KD subjects, with a significant difference. All the investigated inflammatory cytokines (IL-1ß, IL-6, TNF-α) decreased significantly in KDO3 subjects whilst only TNF-α showed a significant decrease in KD subjects over the 12 month study period. No significant changes were observed in anti-inflammatory cytokines (IL-10 and IL-1Ra), creatinine, urea and uric acid. Adiponectin increased significantly only in the KDO3 group. CONCLUSIONS: ω-3 supplementation improved the positive effects of a ketogenic Mediterranean diet with phytoextracts on some cardiovascular/metabolic risk factors and inflammatory state.

Common and divergent molecular mechanisms of fasting and ketogenic diets.

Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality.

Not Only Protein: Dietary Supplements to Optimize the Skeletal Muscle Growth Response to Resistance Training: The Current State of Knowledge.

Regarding skeletal muscle hypertrophy, resistance training and nutrition, the most often discussed and proposed supplements include proteins. Although, the correct amount, quality, and daily distribution of proteins is of paramount importance for skeletal muscle hypertrophy, there are many other nutritional supplements that can help and support the physiological response of skeletal muscle to resistance training in terms of muscle hypertrophy. A healthy muscle environment and a correct whole muscle metabolism response to the stress of training is a prerequisite for the increase in muscle protein synthesis and, therefore, muscle hypertrophy. In this review, we discuss the role of different nutritional supplements such as carbohydrates, vitamins, minerals, creatine, omega-3, polyphenols, and probiotics as a support and complementary factors to the main supplement i.e., protein. The different mechanisms are discussed in the light of recent evidence.