During exercise, lactic acid or lactate is produced in contracting skeletal muscle. Lactic acid acid that is not otherwise used by the cell is cleared from the cell and carried into the blood stream as lactate since hydrogen ion dissociates from lactic acid. Individuals have a resting blood lactate concentration. The more a muscle cell contracts, however, the more lactic acid or lactate is produced in the muscle cell and the more lactic acid is carried into the blood stream as lactate and dissociated hydrogen ion. When the rate of production of lactic acid exceeds the rate of lactate clearance or removal and hydrogen ion buffering capacity, blood lactate concentration increases and blood pH decreases.
The blood lactate concentration for an individual at which the individual has a reduced ability to sustain exercise intensity as manifested, for example, by fatigue is known as the lactate threshold or maximal lactate steady state. A common maximal lactate steady state in an individual is about 4 mmol blood lactate. Individuals with an ability to sustain a higher percentage of their maximum capacity for exercise before reaching maximal lactate steady state tend to be better endurance athletes. That is, an individual's ability to sustain a higher percentage of their maximum capacity for exercise before reaching maximal lactate steady state can be used to predict endurance performance.
A common method for increasing an individual's lactate threshold or for improving an individual's work output at maximal lactate steady state is through exercise training. Regular exercise training increases mitochondrial biogenesis such that the content of mitochondria is increased in muscle. Without wishing to be bound by scientific theory, a higher mitochondrial mass may lead to a lower rate of lactic acid production, an increased clearance rate of lactate (via oxidation) or both for a given level of exercise intensity. As a result, lactate threshold is effectively increased or lactate response during exercise is effectively improved, that is, the individual has the ability to exercise at a higher intensity before exceeding their maximal lactate steady state, for example before a blood lactate concentration of 4 mmol is reached.
Quercetin is a flavonol found in some fruits and vegetables. A cocktail including quercetin, green tea extract, vitamin C, vitamin E, caffeine, niacin, taurine, vitamin B6, vitamin B2, vitamin B1, and glucose was studied and reported to improve cycling time trial performance under certain conditions. However, the investigators recognized that the improved performance could not be attributed to quercetin alone. See MacRae and Mefferd, International Journal of Sport Nutrition and Exercise Metabolism, 2006, 16, 405-419. Quercetin has been reported to increase mouse brain and mouse muscle mitochondrial biogenesis and exercise tolerance in mice. See Davis et al., Am. J. Physiol. Regul. Inter. Comp. Physiol. 296: R1071-R1077 (2009). Quercetin has also been reported to increase maximal oxygen uptake and cycling performance in certain individuals. See Davis et al., International Journal of Sport Nutrition and Exercise Metabolism, 2009, 20, 1013. The effect of quercetin and DMSO on skeletal myogenesis from C2C12 skeletal muscle cells has been reported. See Basic Appl Myol 11 (1): 31-44 (2001). However, none of the studies demonstrated a method of reducing blood lactate concentration by administration of quercetin to an individual, methods of improving muscle cell performance in an individual by reducing blood lactate concentration, or methods of increasing the lactate threshold or the maximal lactate steady state in an individual allowing extended high intensity physical activity.
It is therefore an object of the present invention to reduce blood lactate concentration in an individual by administration of quercetin. It is a further object of the present invention to extend high intensity physical activity by reducing blood lactate concentration. It is a still further object of the present invention to create an assay for identifying compounds capable of reducing lactic acid concentrations in a muscle cell. These and other objects, features, and advantages of the invention or certain embodiments of the invention will be apparent to those skilled in the art from the following disclosure and description of exemplary embodiments.