In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified low carbohydrate diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal. In this study, Aude and colleagues randomized patients to the NCEP diet or an isocaloric MLC diet lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates. Compared with the NCEP diet, the MLC diet caused significantly greater weight loss over 12 weeks.