Controlled feeding studies demonstrate that isocaloric low-fat diets increase energy expenditure and fat loss, which contradicts the carbohydrate-insulin model's proposal that high-carbohydrate diets increase insulin and promote fat storage while reducing energy expenditure.

When a person eats more carbohydrates and less fat while keeping total calories the same, the body burns more calories because digesting and storing carbohydrates and especially protein requires more energy than storing fat. This extra energy use comes from the work of processing amino acids, making new proteins, and removing waste from protein breakdown, which all use up calories. The result is more calories burned and more fat lost, even when eating the same amount of food.