The factors affecting V̇O may be separated into supply and demand. Supply is the transport of oxygen from the lungs to the mitochondria (combining pulmonary function, cardiac output, blood volume, and capillary density of the skeletal muscle) while demand is the rate at which the mitochondria can reduce oxygen in the process of oxidative phosphorylation. Of these, the supply factors may be more limiting. However, it has also been argued that while trained subjects are probably supply limited, untrained subjects can indeed have a demand limitation.
General characteristics that affect V̇O max include age, sex, fitness and training, and altitude. V̇O max can be a poor predictor of performance in runners due to variations in running economy and fatigue resistance during prolonged exercise. The body works as a system. If one of these factors is sub-par, then the whole system's normal capacity is reduced.
The drug erythropoietin (EPO) can boost V̇O max by a significant amount in both humans and other mammals. This makes EPO attractive to athletes in endurance sports, such as professional cycling. EPO has been banned since the 1990s as an illicit performance-enhancing substance. But by 1998 it had become widespread in cycling and led to the Festina affair as well as being mentioned ubiquitously in the USADA 2012 report on the U.S. Postal Service Pro Cycling Team. Greg LeMond has suggested establishing a baseline for riders' V̇O max (and other attributes) to detect abnormal performance increases.