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The need for energy nutrients is high in athletes, and a great deal of science focuses on optimal distribution of the energy substrates to support exercise of different intensities and durations. Studies have demonstrated clearly that dependence on carbohydrate increases with greater exercise intensity, and many studies provide valuable guidelines on how best to deliver carbohydrate to optimize glycogen stores, how best to deliver carbohydrate during training and competition, and how energy substrates contribute to muscle recovery. The contribution of protein to muscle function and recovery is much better understood now than in the recent past, and there is some new science on the relationship between mental and muscle function that is mediated by carbohydrate, protein, and fat. The recent popularity of higher-protein, higher-fat, and lower-carbohydrate diets has serious implications for athletic performance. It is critical that athletes and coaches understand how to assess the appropriate energy intake and energy substrate distribution to optimize both mental and muscle function. This chapter presents the essential elements of carbohydrate, protein, and fat metabolism in exercise, along with a critical scientific view on how these substrates contribute to optimal athletic performance (see table 1.1).