In the 1940s, the diet-heart hypothesis proposed that high dietary saturated fat and cholesterol intake promoted coronary heart disease in "at-risk" individuals. This hypothesis prompted federal recommendations for a low-fat diet for "high risk" patients and as a preventive health measure for everyone except infants. The low carbohydrate diet, first used to treat type 1 diabetes, became a popular obesity therapy with the Atkins diet in the 1970s. Its predicted effectiveness was based largely on the hypothesis that insulin is the causa prima of weight gain and regain via hyperphagia and hypometabolism during and after weight reduction, and therefore reduced carbohydrate intake would promote and sustain weight loss. Based on literature reviews, there are insufficient randomized controlled inpatient studies examining the physiological significance of the mechanisms proposed to support one over the other. Outpatient studies can be confounded by poor diet compliance such that the quality and quantity of the energy intake cannot be ascertained. Many studies also fail to separate macronutrient quantity from quality. Overall, there is no conclusive evidence that the degree of weight loss or the duration of reduced weight maintenance are significantly affected by dietary macronutrient quantity beyond effects attributable to caloric intake. Further work is needed.