The Effects of Dietary Nitrate Supplementation on Explosive Exercise Performance: A Systematic Review

Dietary nitrate supplementation is evidenced to induce physiological effects on skeletal muscle function in fast-twitch muscle fibers and may enhance high-intensity exercise performance. An important component of sport-specific skills is the ability to perform explosive movements; however, it is unclear if nitrate supplementation can impact explosive efforts. We examined the existing evidence to determine whether nitrate supplementation improves explosive efforts lasting ≤ 6 s. PubMed, Scopus and Directory of Open Access Journals (DOAJ) were searched for articles using the following search strategy: (nitrate OR nitrite OR beetroot) AND (supplement OR supplementation) AND (explosive OR power OR high intensity OR high-intensity OR sprint* OR “athletic performance”). Out of 810 studies, 18 were eligible according to inclusion criteria. Results showed that 4 of the 10 sprint-type studies observed improved sprint time, power output, and total work in cycling or running, whereas 4 of the 10 resistance-based exercise studies observed improvements to power and velocity of free-weight bench press as well as isokinetic knee extension and flexion at certain angular velocities. These results suggest that nitrate potentially improves explosive exercise performance, but further work is required to clarify the factors influencing the efficacy of nitrate in different exercise modalities.

Myogenic Differentiation of Human Myoblasts and Mesenchymal Stromal Stem Cells under GDF11 on Poly-ɛ-Caprolactone-Collagen I-Polyethylene-Nanofibers

Primary myoblasts (Mb) and adipose derived mesenchymal stromal cells (ADSC) can be co-cultured and myogenically differentiated in the process of skeletal muscle tissue engineering. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining biocompatibility and stability. Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11.Therefore the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolacton (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers.Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosin heavy chain expression in all groups after 28 days of differentiation. Gene expression of myosin heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.

Klotho: An Emerging Factor With Ergogenic Potential

Sarcopenia and impaired cardiorespiratory fitness are commonly observed in older individuals and patients with chronic kidney disease (CKD). Declines in skeletal muscle function and aerobic capacity can progress into impaired physical function and inability to perform activities of daily living. Physical function is highly associated with important clinical outcomes such as hospitalization, functional independence, quality of life, and mortality. While lifestyle modifications such as exercise and dietary interventions have been shown to prevent and reverse declines in physical function, the utility of these treatment strategies is limited by poor widespread adoption and adherence due to a wide variety of both perceived and actual barriers to exercise. Therefore, identifying novel treatment targets to manage physical function decline is critically important. Klotho, a remarkable protein with powerful anti-aging properties has recently been investigated for its role in musculoskeletal health and physical function. Klotho is involved in several key processes that regulate skeletal muscle function, such as muscle regeneration, mitochondrial biogenesis, endothelial function, oxidative stress, and inflammation. This is particularly important for older adults and patients with CKD, which are known states of Klotho deficiency. Emerging data support the existence of Klotho-related benefits to exercise and for potential Klotho-based therapeutic interventions for the treatment of sarcopenia and its progression to physical disability. However, significant gaps in our understanding of Klotho must first be overcome before we can consider its potential ergogenic benefits. These advances will be critical to establish the optimal approach to future Klotho-based interventional trials and to determine if Klotho can regulate physical dysfunction.

Receptor interacting protein kinase-3 promotes both myopathy and cardiomyopathy in dystrophin-deficient mice

Background Duchenne muscular dystrophy (DMD) is a muscle degenerative disorder that is caused by the absence of dystrophin. From early childhood, multiple rounds of myofibre necrosis and regeneration lead to fibrosis and fat deposition, irreversibly disturbing skeletal muscle function and impairing locomotion. Cell necrosis also affects respiratory muscles and cardiomyocytes, ultimately responsible for the death of DMD boys by respiratory or heart failure. Necroptosis is a genetically programmed form of necrosis requiring the receptor-interacting serine/threonine-protein kinase (RIPK)3 and is a promising new therapeutic target for multiple degenerative disorders. We previously demonstrated that necroptosis mediates hindlimb myofibre degeneration in distinct muscular dystrophies, including in DMD. However, this pathway was recently found to be required for myogenesis. Its prevention might therefore lead to detrimental side effects on muscle repair. Whether necroptosis also participates in the pathogenesis of respiratory and cardiac muscle dysfunction, and whether its long-term inhibition would ultimately be beneficial or detrimental to mdx mice are addressed here. Methods Herein, we examined the effects of RIPK3 depletion on an advanced stage of pathogenesis in mdx mice. Dystrophic mice aged 12 to 18 months were submitted to forced treadmill running to assess their locomotor function. mdx cardiomyopathy was also examined by echocardiography in 40-week-old mice. Limb skeletal muscles, diaphragm and heart were analyzed by histology and molecular biology to compare the phenotype of mdxRipk3+/+ mdxRipk3-/- mice. Results In 18-month-old mdxRipk3-/- mice, we found no sign of muscle regeneration defect compared to mdxRipk3+/+ littermates. mdxRipk3-/- mice had decreased fibrosis in limb muscles, without evidence of muscle atrophy. The size of diaphragm myofibres was slightly reduced and affected by less variability than mdx littermates. Fibrosis was also reduced in the diaphragm of RIPK3-deficient mdx mice. Notably, heart hypertrophy and left ventricle fibrosis were reduced in mdxRipk3-/- mice, and using echocardiography, we found a significant decrease of markers of cardiomyopathy by such as a reduction of the relative wall thickness and left ventricle mass. Conclusions Our data suggest that necroptosis is involved together in the pathogenic phenotype of locomotor, respiratory, and cardiac muscles in dystrophin-deficient mice. The long-term genetic ablation of RIPK3 does not generate evidence of sarcopenia or muscle impairment in mdx mice. Our data suggest that necroptosis may represent a new therapeutic target susceptible to improving the phenotype of myopathy and cardiomyopathy.

Predictors of Prolonged Cardiopulmonary Exercise Impairment After COVID-19 Infection: A Prospective Observational Study

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment.Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3–6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50).Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO2 peak - % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO2 peak; p = 0.013 and VT2/VO2 peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R2) of the variance in relative VO2 peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO2 peak, which were related to higher relative VO2 peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV.Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3–6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO2 peak in those patients, which may have important implications on rehabilitation programs.

Exercise as a Peripheral Circadian Clock Resynchronizer in Vascular and Skeletal Muscle Aging

Aging is characterized by several progressive physiological changes, including changes in the circadian rhythm. Circadian rhythms influence behavior, physiology, and metabolic processes in order to maintain homeostasis; they also influence the function of endothelial cells, smooth muscle cells, and immune cells in the vessel wall. A clock misalignment could favor vascular damage and indirectly also affect skeletal muscle function. In this review, we focus on the dysregulation of circadian rhythm due to aging and its relationship with skeletal muscle changes and vascular health as possible risk factors for the development of sarcopenia, as well as the role of physical exercise as a potential modulator of these processes.

Enhanced Muscle Strength in Dyslipidemic Mice and Its Relation to Increased Capacity for Fatty Acid Oxidation

Dyslipidemia is commonly linked to skeletal muscle dysfunction, accumulation of intramyocellular lipids, and insulin resistance. However, our previous research indicated that dyslipidemia in apolipoprotein E and low-density lipoprotein receptor double knock-out mice (ApoE/LDLR -/-) leads to improvement of exercise capacity. This study aimed to investigate in detail skeletal muscle function and metabolism in these dyslipidemic mice. We found that ApoE/LDLR -/- mice showed an increased grip strength as well as increased troponins, and Mhc2 levels in skeletal muscle. It was accompanied by the increased skeletal muscle mitochondria numbers (judged by increased citrate synthase activity) and elevated total adenine nucleotides pool. We noted increased triglycerides contents in skeletal muscles and increased serum free fatty acids (FFA) levels in ApoE/LDLR -/- mice. Importantly, Ranolazine mediated inhibition of FFA oxidation in ApoE/LDLR -/- mice led to the reduction of exercise capacity and total adenine nucleotides pool. Thus, this study demonstrated that increased capacity for fatty acid oxidation, an adaptive response to dyslipidemia leads to improved cellular energetics that translates to increased skeletal muscle strength and contributes to increased exercise capacity in ApoE/LDLR -/- mice.