The present invention relates to the use of a low-caloric high-protein nutritional composition for use in the prevention or treatment of a disease or condition in a mammal, which involves muscle decline, as well as to specific low-caloric high-protein nutritional compositions for stimulating muscle protein synthesis in a mammal. In particular, the invention relates to the use of a nutritional composition comprising per 100 kcal : (i) at least about 12 g of proteinaceous matter which comprises at least about 80 weight% of whey protein, relative to the total proteinaceous matter, and which comprises at least about 11 weight% of leucine, relative to the total proteinaceous matter, of which at least about 20 weight% is in a free form, relative to the total leucine, (ii) a source of fat and a source of digestible carbohydrates, for the prevention or treatment of a disease or condition which involves muscle decline in a mammal, especially an elderly mammal, wherein the nutritional composition is administered as 1 to 2 servings daily, each serving comprising between 80 and 200 kcal.