The concept of the "Calorie" originated in the 1800 s in an environment with limited food availability, primarily as a means to define economic equivalencies in the energy density of food substrates. Soon thereafter, the energy densities of the major macronutrients-fat, protein, and carbohydrates-were defined. However, within a few decades of its inception, the "Calorie" became a commercial tool for industries to promote specific food products, regardless of health benefit. Modern technology has altered our living conditions and has changed our relationship with food from one of survival to palatability. Advances in agriculture, food manufacturing, and processing have ensured that calorie scarcity is less prevalent than calorie excess in the modern world. Yet, many still approach dietary macronutrients in a reductionist manner and assume that isocalorie foodstuffs are isometabolic. Herein, we discuss a novel way to view the major food macronutrients and human diet in this era of excessive caloric consumption, along with a novel relationship among calorie scarcity, mild cold stress, and sleep that may explain the increasing prevalence of nutritionally related diseases.