Effect of a Moderate-Intensity Aerobic Training on Joint Biomarkers and Functional Adaptations in Rats Subjected to Induced Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis (kOA) is a common chronic disease that induces changes in redox status and inflammatory biomarkers, cell death, and motor impairment. Aerobic training can be a non-pharmacological alternative to prevent the progression of the disease. OBJECTIVE: To evaluate the effects of an 8 weeks moderate-intensity treadmill aerobic training program on redox status and inflammatory biomarkers and motor performance in kOA-like changes induced by monosodium iodoacetate (MIA) in rats. METHODS: Twenty-seven rats were randomly divided into three groups: SHAM; induced kOA (OA); and induced kOA + aerobic training (OAE). Motor performance was evaluated by the number of falls on rotarod test, the total time of displacement and the number of failures on a 100 cm footbridge. Data for cytokines and histology were investigated locally, whereas plasma was used for redox status biomarkers. RESULTS: The OA group, compared to the SHAM group, increased 1.13 times the total time of displacement, 6.05 times the number of failures, 2.40 times the number of falls. There was also an increase in cytokine and in thiobarbituric acid reactive substances (TBARS) (IL1ß: 5.55-fold, TNF: 2.84-fold, IL10: 1.27-fold, IL6: 1.50-fold, TBARS: 1.14-fold), and a reduction of 6.83% in the total antioxidant capacity (FRAP), and of 35% in the number of chondrocytes. The aerobic training improved the motor performance in all joint function tests matching to SHAM scores. Also, it reduced inflammatory biomarkers and TBARS level at values close to those of the SHAM group, with no change in FRAP level. The number of falls was explained by IL1ß and TNF (58%), and the number of failures and the total time of displacement were also explained by TNF (29 and 21%, respectively). CONCLUSION: All findings indicate the efficacy of moderate-intensity aerobic training to regulate inflammatory biomarkers associated with improved motor performance in induced kOA-like changes, thus preventing the loss of chondrocytes.

Acute exercise does not impair renal function in nondialysis chronic kidney disease patients regardless of disease stage.

Exercise has been overlooked as a potential therapy in chronic kidney disease (CKD), mainly because of a lack of understanding on its safety aspects. Notably, there are no data on renal function after exercise in CKD considering its stages. We investigated the acute effects of a 30-min moderate-intensity aerobic exercise bout on glomerular filtration rate (GFR) and albuminuria in 22 nondialysis CKD patients divided into: CKD stages 1 and 2 (CKD1-2) and CKD stages 3 and 4 (CKD3-4). Eleven body mass index-, age-, and sex-matched healthy individuals served as control (CON). Blood and urine samples were collected before, immediately after, and up to 90 min postexercise for creatinine and albumin assessments. GFR was determined by creatinine clearance (GFRCr-Cl). All CKD patients had significantly lower peak oxygen uptake than CON. CKD1-2 and CKD3-4 had increasingly higher serum creatinine than CON (9.6 ± 2.6, 25.6 ± 1.01, and 7.5 ± 1.4 mg/l, respectively); however, no within-group changes in serum or urinary creatinine were observed across time. GFRCr-Cl was decreased in CKD1-2 and CKD3-4 compared with CON (91 ± 17 ml·min-1·1.73 m-2; 34 ± 15 ml·min-1·1.73 m-2; 122 ± 20 ml·min-1·1.73 m-2, respectively). Most importantly, exercise did not affect GFRCr-Cl in none of the groups across time. Albuminuria was significantly higher in CKD3-4 (297 ± 284 µg/min) than in CON (5.4 ± 1.4 µg/min), but no within-group changes were observed after exercise. In conclusion, a single 30-min moderate-intensity aerobic exercise bout does not impair renal function in nondialysis CKD patients, regardless of disease stage, supporting the notion that exercise training can be safe in this disease.

Protein metabolism and physical training: any need for amino acid supplementation?

Muscle mass is the major deposit of protein molecules with dynamic turnover between net protein synthesis and degradation. In human subjects, invasive and non-invasive techniques have been applied to determine their skeletal muscle catabolism of amino acids at rest, during and after different forms of physical exercise and training. The aim of this review is to analyse the turnover flux and the relative oxidation rate of different types of muscle proteins after one bout of exercise as well as after resistance and endurance condition of training. Protein feeding in athletes appears to be a crucial nutrition necessity to promote the maintenance of muscle mass and its adaptation to the need imposed by the imposed technical requirements. In resting human individuals, there commended protein daily allowance is about 0.8 g (dry weight) kg−body weight per 24 h knowing that humans are unable to accumulate protein stores in muscle tissues. Nevertheless, practical feeding recommendations related to regular exercise practice are proposed to athletes by different bodies in order to foster their skills and performance. This review will examine the results obtained under endurance and resistance type of exercise while consuming single or repeated doses of various ingestions of protein products (full meat, essential amino acids, specific amino acids and derivatives, vegetarian food). From the scientific literature, it appears that healthy athletes(and heavy workers) should have a common diet of 1.25 g kg−24 h to compensate the exercise training muscle protein degradation and their resyn thesis within the following hours. A nitrogen-balance assay would berecommended to avoid any excessive intake of protein. Eventually, a daily equilibrated food intake would beof primer importance versus inadequate absorption of some specific by-products.

Nitrate supplementation and human exercise performance: too much of a good thing?

PURPOSE OF REVIEW: Ergogenic supplements in sport events are widely used by popular and competitive athletes to enhance performance and reduce oxygen cost. Beetroot juice and nitrate salts have been increasingly used for the past 5-6 years. The present review discusses the scientific background, the efficiency and potential adverse effects of excessive nitrate supplementation. RECENT FINDINGS: There is clear evidence that nitrate from different food ingredients (such as beetroot juice and other vegetables) is converted into nitrite and possibly into nitric oxide, which may promote vasodilation, angiogenesis and mitochondrial biogenesis. The high affinity of nitric oxide towards different enzyme pathways inhibits excessive mitochondrial respiration and, therefore, tissue oxygen consumption. In addition, L-arginine supplements are proposed to stimulate nitric oxide synthesis in the endothelium. On the basis of these biochemical properties, nitrate supplementation has been suggested to athletes to enhance exercise performance. SUMMARY: The recent publications in human individuals based on L-arginine, beetroot juice or nitrate supplementation revealed either a minor positive effect or no systematic effect on exercise performance, especially in trained athletes. Of note, the sugar content of whole beetroot juice might induce a slightly more pronounced effect. Although reasonable intake of nitrate salts (up to 1 g/day) has no detrimental effect on kidney function, the risk and benefit of higher nitrate intake needs to be evaluated to define the optimal range of supplementation.

Can creatine supplementation form carcinogenic heterocyclic amines in humans?

There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens.

Metabolic regulation during sport events: factual interpretations and inadequate allegations

Different fuels are available to generate ATP for muscle activities during sport events. Glycogen from striated muscles and liver stores may be converted to lactic acid or almost completely oxidized to carbon dioxide (CO2), triacylglycerol within the muscle itself and fatty acids from adipose tissue could be converted to CO2 in acting muscles, some free amino acids can be released within the muscle itself and from intestinal stores to sustain the amount of ATP generation indispensable for muscle contraction. All single biochemical reactions, but one, need one or several enzymes to activate the conversion of a substrate into a product. The energy transformation in biochemical reactions is led by application of so-called free energy. Reversible and non-reversible reactions within a metabolic pathway are dependent on specific enzymes near or far from equilibrium. Allosteric enzymes are regulatory enzymes that provide the direction in the pathway. A regulatory enzyme is either activated or inhibited by small regulators (ligands). A reversible substrate cycle between A and B is catalyzed by two enzymes with different fluxes. The need of ATP production for muscle contraction is under the leadership of regulatory enzymes and available substrate stores. The improvement of adapted metabolic reactions under sport training depends on the appropriate increase of regulatory enzymes within the glycolytic and oxidative pathways. The amount of some specific enzymes is increased by training in order to improve the maximum activity of the metabolic pathway. Unfortunately, several publications do not precisely implicate the appropriate enzyme(s) to explain or reject the adaptation induced by the training schedule. A few examples will illustrate the factual interpretation and the inadequate allegation...

Renewed avenues through exercise muscle contractility and inflammatory status.

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.

Exploring the therapeutic role of creatine supplementation.

Creatine (Cr) plays a central role in energy provision through a reaction catalyzed by phosphorylcreatine kinase. Furthermore, this amine enhances both gene expression and satellite cell activation involved in hypertrophic response. Recent findings have indicated that Cr supplementation has a therapeutic role in several diseases characterized by atrophic conditions, weakness, and metabolic disturbances (i.e., in the muscle, bone, lung, and brain). Accordingly, there has been an evidence indicating that Cr supplementation is capable of attenuating the degenerative state in some muscle disorders (i.e., Duchenne and inflammatory myopathies), central nervous diseases (i.e., Parkinson's, Huntington's, and Alzheimer's), and bone and metabolic disturbances (i.e., osteoporosis and type II diabetes). In light of this, Cr supplementation could be used as a therapeutic tool for the elderly. The aim of this review is to summarize the main studies conducted in this field and to highlight the scientific and clinical perspectives of this promising therapeutic supplement.

The effect of 5 days of aspartate and asparagine supplementation on glucose transport activity in rat muscle.

The consumption of protein supplements containing amino acids is increasing around the world. Aspartate (Asp) and asparagine (Asn) are amino acids metabolized by skeletal muscle. This metabolism involves biochemical pathways that are involved in increasing Krebs cycle activity via anaplerotic reactions, resulting in higher glutamine concentrations. A connection between amino acid supplementation, glycogen concentration, and glucose uptake has been previously demonstrated. The purpose of this study was to evaluate the effect of Asp and Asn supplementation on glucose uptake in rats using three different glycogen concentrations. The results indicate that Asp and Asn supplementation in rats with high glycogen concentrations (fed state) further increased the glycogen concentration in the muscle, and decreased in vitro 2-deoxyglucose (a glucose analog) uptake by the muscle at maximal insulin concentrations. When animals had a medium glycogen concentration (consumed lard for 3 days), glucose uptake was higher in the supplemented group at sub-maximal insulin concentrations. We conclude that supplementation of Asp and Asn reduced glucose transport in rat muscle only at higher levels of glycogen. The ingestion of lard for 3 days changed the responsiveness and sensitivity to insulin, and that group had higher levels of insulin sensitivity with Asp and Asn supplementation.