Processing food extensively by thermal and nonthermal techniques is a unique and universal human practice. Food processing increases palatability and edibility and has been argued to increase energy gain. Although energy gain is a well-known effect from cooking starch-rich foods, the idea that cooking meat increases energy gain has never been tested. Moreover, the relative energetic advantages of cooking and nonthermal processing have not been assessed, whether for meat or starch-rich foods. Here, we describe a system for characterizing the energetic effects of cooking and nonthermal food processing. Using mice as a model, we show that cooking substantially increases the energy gained from meat, leading to elevations in body mass that are not attributable to differences in food intake or activity levels. The positive energetic effects of cooking were found to be superior to the effects of pounding in both meat and starch-rich tubers, a conclusion further supported by food preferences in fasted animals. Our results indicate significant contributions from cooking to both modern and ancestral human energy budgets. They also illuminate a weakness in current food labeling practices, which systematically overestimate the caloric potential of poorly processed foods.caloric value | nutrition label | weight | energy balance | human evolution E nergy availability is a routine constraint on metabolic processes, including growth, disease suppression, and reproduction, and therefore, it is a key variable for human nutrition and evolutionary fitness. Cooking has long been recognized to increase the energy available from starch (1-3), but how it changes the rate of energy gain from eating meat is an unsolved problem with practical and theoretical implications. Because meat is nearly always eaten cooked, the contribution of meat cooking to human nutritional energetics is potentially great: meat is the largest source of protein in all affluent countries except Japan (4), and dependence on meat is growing rapidly among developing nations (5), with annual global consumption of meat expected to reach 376 million tons by 2030 (6). The energetic consequences of cooking meat would also have been important in human evolution ever since fire was controlled, minimally 300,000-400,000 y ago, a period when meat is inferred to have been a large component of the diet and energy would have routinely been in short supply (7-9).The standard Atwater system of energy assessment is based on measuring the total metabolizable nutrient content of an edible item (gross food energy content minus energy lost in urine, feces, secretions, and gases) and finds that cooking tends to have minimal impact on meat energy value (10) ( Table S1). However, this conclusion is suspect, because the Atwater system ignores potentially important effects (1). Heat-induced protein denaturation, loss of structural integrity, and deactivation of microbes are expected to increase meat energy value (2, 11, 12), whereas dripping loss, Maillard reactions, formation of protein c...