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BASSETT, D. R., JR. and E. T. HOWLEY. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med. Sci. Sports Exerc., Vol. 32, No. 1, pp. 70–84, 2000. In the exercising human, maximal oxygen uptake (V̇O2max) is limited by the ability of the cardiorespiratory system to deliver oxygen to the exercising muscles. This is shown by three major lines of evidence: 1) when oxygen delivery is altered (by blood doping, hypoxia, or beta-blockade), V̇O2max changes accordingly; 2) the increase in V̇O2max with training results primarily from an increase in maximal cardiac output (not an increase in the a- O2 difference); and 3) when a small muscle mass is overperfused during exercise, it has an extremely high capacity for consuming oxygen. Thus, O2 delivery, not skeletal muscle O2 extraction, is viewed as the primary limiting factor for V̇O2max in exercising humans. Metabolic adaptations in skeletal muscle are, however, critical for improving submaximal endurance performance. Endurance training causes an increase in mitochondrial enzyme activities, which improves performance by enhancing fat oxidation and decreasing lactic acid accumulation at a given V̇O2. V̇O2max is an important variable that sets the upper limit for endurance performance (an athlete cannot operate above 100% V̇O2max. for extended periods). Running economy and fractional utilization of V̇O2max also affect endurance performance. The speed at lactate threshold (LT) integrates all three of these variables and is the best physiological predictor of distance running performance.