There is abundant evidence that dietary protein stimulates protein breakdown and re-synthesis. In particular, branched chain amino acids, and especially leucine, are documented to act as nutritional signals acting via both the insulin and mTOR signaling pathways [16-18]. On the macroscopic level, the energetic cost of protein turnover is demonstrable as excess heat generated during a high protein meal. Thermogenesis (thermogenic effect of feeding; old name: specific dynamic action) has been defined as the extra heat generated during a meal due to digestion or metabolism. Johnston et al [19] compared the energy expended during 9 hour intravenous feedings of a high protein meal, vs. an isocaloric high carbohydrate meal; both contrasted with a 9 hour fast. The protein meal, with 70% of its caloric value due to protein, had significantly greater thermogenesis than the high carbohydrate meal (70% of calories from carbohydrate). These data have been reproduced in numerous studies [19-22]. The overall energy costs of protein turnover and synthesis have been estimated in various animal species, including man, and tabulated by Vernon Young ([23]), based on data from other investigators [24-26]. Despite the substantial experimental difficulties involved, the cost of protein synthesis clusters at around 4–5 kcal/gram in 8 species of birds, marsupials and mammals, including man. The high energetic cost is understandable in view of the multiple ATP-requiring processes involved. The cost of protein turnover can reduce efficiency from 33% to 27%, merely in the formation and hydrolysis of a single peptide bond (requiring 4 ATP's per bond formed: Table 1). In addition, protein processes that are ATP-dependent include formation of the ribosomal initiation complex, translation and folding of the protein, and protein degradation (both ubiquitin-dependent and -independent pathways) [23]. The energy costs of protein turnover could therefore account for a metabolic advantage in high protein diets, independent of carbohydrate content. This mechanism may also contribute to inefficiency in low carbohydrate diets, often high in protein.