Reducing muscle fatigue

#The present invention relates to muscle fatigue and particularly but not exclusively to a method for reducing muscle fatigue in humans.

#Pyruvate is known to be present in the muscles of vertebrates. It is produced naturally in the body by glycolysis in the cytosol of cells. During aerobic exercise the pyruvate can be completely oxidised through the Tricarboxylic acid cycle (TCA cycle) in mitochondria. During prolonged exercise the muscle pool of TCA cycle intermediates can become deleted which has been suggested to reduce the rate of the cycle and hence reduce the rate at which the muscle produces energy, which may result in fatigue.

#It has recently been demonstrated that there is a lag in the activation of mitochondrial energy production in the muscle at the beginning of exercise, in which instance muscle will use anaerobic systems such as converting pyruvate to lactate to compensate for the energy deficit. This can lead to the muscle activity being impaired and can result in muscle fatigue. Similarly, during more prolonged exercise mitochondrial respiration has been suggested to be comprised, resulting in fatigue (Sahlinstal 1990).

#Six men were intravenously infused for 30 minutes with a pyruvate solution at a rate of 1.67 mg.kgbody mass.sup.-1.min.sup.-1. Muscle biopsy samples, obtained from the vastus lateralis immediately before and after each infusion, were analysed for the concentration of pyruvate dehydrogenase complex (PDC), and pyruvate metabolites such as TCA cycle intermediates, in skeletal muscle. The results are shown in the following table.

#______________________________________ Pyruvate Pre Post ______________________________________ PDCa.sup.1 0.36 .+-. 0.05 0.35 .+-. 0.10 Pyruvate.sup.2 0.18 .+-. 0.02 0.26 .+-. 0.07 Lactate.sup.2 4.31 .+-. 0.74 4.82 .+-. 0.62 Acetylcarnitine.sup.2 2.78 .+-. 0.53 1.97 .+-. 0.26 Citrate.sup.2 0.34 .+-. 0.01 0.38 .+-. 0.04 Malate.sup.2 0.24 .+-. 0.03 0.41 .+-. 0.05 2-oxoglutarate.sup.2 0.07 .+-. 0.02 0.08 .+-. 0.01 ETCAP 0.66 .+-. 0.02 0.89 .+-. 0.09 ______________________________________ Values represent mean .+-. SEM. .sup.1 mmol min.sup.-1 kg.sup.-1 wet mass; .sup.2 mmol kg.sup.-1 dry mass

#These results demonstrate that pyruvate infusion significantly increased the concentration of TCA cycle intermediates (TCAI), probably by providing a readily available supply of pyruvate for anaplerosis i.e. conversion of pyruvate into TCA cycle intermediates such as oxaloacetate, malate, and .alpha. keto glutarate.