Short-Term Supplementation of Sodium Nitrate vs. Sodium Chloride Increases Homoarginine Synthesis in Young Men Independent of Exercise.

The aim of the study was to investigate the effects of short-term oral administration of inorganic nitrate (NaNO3; n = 8) or placebo (NaCl; n = 9) (each 0.1 mmol/kg body weight/d for 9 days) on plasma amino acids, creatinine, and oxidative stress in healthy young men. At baseline, the plasma concentrations of amino acids did not differ between the groups. At the end of the study, the plasma concentrations of homoarginine (hArg; by 24%, p = 0.0001), citrulline and ornithine (Cit/Orn; by 16%, p = 0.015), and glutamine/glutamate (Gln/Glu; by 6%, p = 0.0003) were higher in the NaNO3 group compared to the NaCl group. The plasma concentrations of sarcosine (Sarc; by 28%, p < 0.0001), tyrosine (by 14%, p = 0.0051), phenylalanine (by 8%, p = 0.0026), and tryptophan (by 8%, p = 0.0047) were lower in the NaNO3 group compared to the NaCl group. These results suggest that nitrate administration affects amino-acid metabolism. The arginine/glycine amidinotransferase (AGAT) catalyzes two reactions: (1) the formation of l-homoarginine (hArg) and l-ornithine (Orn) from l-arginine (Arg) and l-lysine (Lys): Arg + Lys <−> hArg + Orn, with equilibrium constant Kharg; (2) the formation of guanidinoacetate (GAA) and Orn from Arg and glycine (Gly): Arg + Gly <−> GAA + Orn, with equilibrium constant Kgaa. The plasma Kgaa/KhArg ratio was lower in the NaNO3 group compared to the NaCl group (1.57 vs. 2.02, p = 0.0034). Our study suggests that supplementation of inorganic nitrate increases the AGAT-catalyzed synthesis of hArg and decreases the N-methyltransferase-catalyzed synthesis of GAA, the precursor of creatine. To our knowledge, this is the first study to demonstrate elevation of hArg synthesis by inorganic nitrate supplementation. Remarkably, an increase of 24% corresponds to the synthesis capacity of one kidney in healthy humans. Differences in the association between plasma concentrations of amino acids in the NaNO3 and NaCl groups suggest changes in amino-acid homeostasis. Plasma concentrations of the oxidative stress marker malondialdehyde (MDA) did not change after supplementation of NaNO3 or NaCl over the whole exercise time range. Plasma nitrite concentration turned out to be a more discriminant marker of NaNO3 ingestion than plasma nitrate (area under the receiver operating characteristic curve: 0.951 vs. 0.866, p < 0.0001 each).

Skeletal Muscle Function in Young Patients With Cystic Fibrosis.

PURPOSE: Defects in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) cause CF. Absence of the CFTR may result in skeletal muscle dysfunction. Here, we tested skeletal muscle function in male adolescent patients with CF. METHODS: Ten CF and 10 control participants (age: 16.8 ± 0.6 years) performed 7 repetitive sets of maximum voluntary contractions (MVCs) and underwent an isometric fatigue test of the knee extensors. Electromyography (EMG) activity was recorded from the m. vastus lateralis (VL) and m. vastus medialis (VM). RESULTS: In CF, the MVC torque was lower and correlated with the predicted forced expiratory volume in one second (r = .73, p = .012, n = 10). The M-wave in the VL was shorter in CF than in controls (18.6 ± 0.5 vs. 20.3 ± 0.5 ms, p < .028). In the VM, both the M-wave (4.96 ± 0.61 vs. 7.97 ± 0.60 mV, p = .001) and the EMG (0.29 ± 0.04 vs. 0.47 ± 0.04 mV, p = .004) amplitudes were smaller in CF. CONCLUSION: The differences in the VL and VM EMG signals between the groups indicate that the lower MVC torque in CF did not result from the direct impact of a CFTR defect on the sarcolemmal excitability; the differences more likely resulted from the less developed musculature in the patients with CF.

The effects of creatine pyruvate and creatine citrate on performance during high intensity exercise.

BACKGROUND: A double-blind, placebo-controlled, randomized study was performed to evaluate the effect of oral creatine pyruvate (Cr-Pyr) and creatine citrate (Cr-Cit) supplementation on exercise performance in healthy young athletes. METHODS: Performance during intermittent handgrip exercise of maximal intensity was evaluated before (pretest) and after (posttest) 28 days of Cr-Pyr (5 g/d, n = 16), Cr-Cit (5 g/d, n = 16) or placebo (pla, 5 g/d, n = 17) intake. Subjects performed ten 15-sec exercise intervals, each followed by 45 sec rest periods. RESULTS: Cr-Pyr (p < 0.001) and Cr-Cit (p < 0.01) significantly increased mean power over all intervals. Cr-Cit increased force during the first and second interval (p < 0.01) compared to placebo. The effect of Cr-Cit on force decreased over time and the improvement was not significant at the sixth and ninth interval, whereas Cr-Pyr significantly increased force during all intervals (p < 0.001). Cr-Pyr (p < 0.001) and Cr-Cit (p < 0.01) resulted in an increase in contraction velocity, whereas only Cr-Pyr intake significantly (p < 0.01) increased relaxation velocity. Oxygen consumption measured during rest periods significantly increased with Cr-Pyr (p < 0.05), whereas Cr-Cit and placebo intake did not result in significant improvements. CONCLUSION: It is concluded that four weeks of Cr-Pyr and Cr-Cit intake significantly improves performance during intermittent handgrip exercise of maximal intensity and that Cr-Pyr might benefit endurance, due to enhanced activity of the aerobic metabolism.

Energy metabolism in intensively exercising calf muscle under a simulated orthostasis.

We conducted non-invasive methods to investigate the mechanisms how an orthostasis improves fatigue resistance in human calf muscle during intense exercise. Eleven healthy volunteers performed two series of ten intervals of maximum dynamic exercise (15 s) and recovery (45 s) at almost horizontal body position under both, control conditions (CON) and lower body negative pressure (LBNP, -40 mbar). As from the second work interval, LBNP significantly improved fatigue resistance shown as a lower reduction in work and in contraction velocity (P < 0.01). During each work interval, EMG showed a small increase in amplitude (P < 0.01) and a steep drop by 20% in median frequency (P < 0.01). Under LBNP, both EMG parameters completely recovered during subsequent rest, whereas under CON recovery was incomplete (P < 0.01). During the first work interval, consumption of phosphocreatine (PCr) was almost the same for both conditions. In periods of recovery under LBNP, resynthesis of PCr and inorganic phosphate were significantly faster. PCr reached 10 to 20% higher levels (P < 0.01). LBNP caused an initial increase in intracellular pH (0.08 U (P < 0.01)). The subsequent time courses of pH were similar for CON and LBNP. During work, pH steeply increased by about 0.3 U. During subsequent recovery, pH dropped to values between 6.3 and 6.5. LBNP caused significantly higher levels of total haemoglobin and oxy-haemoglobin (P < 0.05). A simulated orthostasis increased fatigue resistance during high intense interval exercise because of a faster PCr resynthesis and may be because of improvements in the maintenance of motoneuronal activity.

The relationships between plasma potassium, muscle excitability and fatigue during voluntary exercise in humans.

The relationships between extracellular potassium elevation and EMG variables in relation to muscle fatigue were investigated during handgrip exercise in humans. Acid-base state, lactate, potassium ([K+](v)) and sodium in venous plasma, as well as variables of surface voluntary and evoked (M-wave) EMG were determined during repeated dynamic (DE) and static (SE) exercise (1 min exercise, 4 min rest). The different rises of [K+](v) were induced by randomly varied workloads. After 15 min of warming up, the M-wave area increased to 124.9 +/- 19.6% (P < 0.001) in comparison with the control value. Simultaneously, the [K+](v) decreased from 4.1 +/- 0.3 to 3.6 +/- 0.3 mmol l(-1) (P < 0.01). During both SE and DE, there were marked intensity-dependent signs of fatigue. The [K+](v) correlated with changes of the integrated EMG (r = 0.87, P < 0.001 for both DE and SE). Changes in the M-wave area during the exercise bouts correlated inversely with the [K+](v) (r = -0.73, P < 0.001). The M-wave area did not decrease below the control value at any intensity. The median frequency of the EMG decreased during exercise, depending on the exercise intensity (r = -0.73 for SE, r = -0.47 for DE, P < 0.001) with a maximal decrease to about 80% after SE with the maximal workload. The muscle action potential propagation velocity changed in the range of about +/-2%. For the first time, a negative relationship between venous potassium and M-wave area was shown during voluntary exercise. However, there was no evidence that the decrease in muscle performance was mainly caused by a decrease in sarcolemmal excitability resulting from a high extracellular [K+].