One of the most pervasive weight loss rules is that a cumulative energy deficit of 3500 kcal is required per pound of body weight loss, or equivalently 32.2 MJ kg À1 . Under what conditions is it appropriate to use this rule of thumb and what are the factors that determine the cumulative energy deficit required per unit weight loss? Here, I examine this question using a modification of the classic Forbes equation that predicts the composition of weight loss as a function of the initial body fat and magnitude of weight loss. The resulting model predicts that a larger cumulative energy deficit is required per unit weight loss for people with greater initial body fatFa prediction supported by published weight loss data from obese and lean subjects. This may also explain why men can lose more weight than women for a given energy deficit since women typically have more body fat than men of similar body weight. Furthermore, additional weight loss is predicted to be associated with a lower average cumulative energy deficit since a greater proportion of the weight loss is predicted to result from loss of lean body mass, which has a relatively low energy density in comparison with body fat. The rule of thumb approximately matches the predicted energy density of lost weight in obese subjects with an initial body fat above 30 kg but overestimates the cumulative energy deficit required per unit weight loss for people with lower initial body fat. International Journal of Obesity (2008) When energy intake does not meet energy requirements, the deficit is accounted for by metabolism of stored energy in the form of body fat, protein and glycogen. Since energy is conserved, the metabolizable energy content of the lost tissue is equivalent to the energy deficit required to produce that weight loss. The metabolizable energy density of the lost tissue is therefore determined by its chemical composition. Loss of body water results in a significant mass change, but contributes nothing to the metabolizable energy content. In contrast, the metabolizable energy densities of body glycogen, protein and fat are 17.6, 19.7 and 39.5 MJ kg À1 , respectively. 5 Recently, I developed a modification of the classic Forbes equation 3,4 predicting the proportion of weight loss accounted for by loss of lean body mass as a nonlinear function of both the initial body fat as well as the magnitude of weight loss. 6 On the basis of this equation, the energy density of weight loss can be predicted once the metabolizable energy densities for the lean body mass loss, DL, and body fat mass loss, DF, have been determined.The energy density of the body fat mass change, r F ¼ 39.5 MJ kg À1 is the same as the energy density of fat. It is important to note that the change of body fat, DF, is not equivalent to the loss of adipose tissue, which includes a variable contribution of fluid and protein in addition to triglyceride. 7,8 Rather, DF is the amount of endogenous fat metabolized by the body to meet the energy deficit. Similarly, the energy density of the lea...