Background: Dietary protein is considered the most satiating macronutrient, yet there is little evidence on whether the effects observed are attributable to the protein or to the concomitant manipulation of carbohydrates and fat. Objective: The aim was to examine the effect of consumption of preloads varying in macronutrient content on appetite, energy intake, and biomarkers of satiety. Methods: Using a randomized, within-subjects, 2-level factorial design, 36 adults [mean +/- SD age: 27 +/- 5 y; body mass index (in kg/m(2)): 24.3 +/- 1.6) received a breakfast consisting of 1 of 7 isovolumetric (670 mL) and isoenergetic (2100 kJ) liquid preloads matched for energy density and sensory properties but with different macronutrient composition (levels: 9%, 24%, or 40% of energy from protein combined with a carbohydrate-to-fat ratio of 0.4, 2, or 3.6, respectively). Appetite ratings and blood samples were collected and assessed at baseline and every 30 and 60 min, respectively, until a lunch test meal, which participants consumed ad libitum, was served 3.5 h after breakfast. Results: Prospective consumption was 12% lower after intake of the high-protein (40%)/3.6 carbohydrate: fat preload than after intake of the low-protein (9%)/0.4 carbohydrate: fat preload (P = 0.02) solely because of the increased protein, irrespective of the manipulation of the other macronutrients. Most appetite ratings tended to be suppressed (13%) with increasing protein content of the preloads (P < 0.06). Carbohydrate elicited greater increases in fullness and postprandial responses of glucose and insulin than did protein and fat. The glucose concentration was suppressed and glucagon-like peptide 1 increasedmore after intake of the high-protein (40%)/0.4 carbohydrate: fat preload than after the other preloads (P < 0.001). No statistically significant differences in postprandial ghrelin release or ad libitum energy intake at lunch were found. Conclusions: By varying all 3 macronutrients simultaneously and in a systematically balanced manner, we found that protein had a more pronounced effect on suppressing appetite than did carbohydrates and fat. Modulating the nutritional profile of a meal by replacing fat with protein can influence appetite in healthy adults. This trial was registered at www.clinicaltrials.gov as NCT01849302.
