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Little is known about human postprandial increase of energy expenditure and satiety-associated hormones in relation to both meal frequency and macronutrient composition.Randomized cross-over study with four conditions for each participant.Seven men and seven women (mean age 23±1.5years) were randomly assigned to the order of intake of a 750kcal drink with the same protein content while having either 20 energy-percent (E%) or 55 E% from carbohydrates and the remaining energy from fat. Participants were also randomized to consume the drinks as one large beverage or as five 150kcal portions every 30min, starting in the fasting state in the morning. Energy expenditure (EE) was determined every 30min by indirect calorimetry. Hormonal responses and suppression of hunger (by visual-analogue scales) were also studied. A p0.013 was considered statistically significant following Bonferroni-correction.The area under the curve (AUC) for EE was higher during the 2.5h after the high-carbohydrate drinks (p=0.005 by Wilcoxon) and also after ingesting one drink compared with five (p=0.004). AUC for serum active GLP-1 was higher after single drinks compared with five beverages (p=0.002). Although GLP-1 levels remained particularly high at the end of the test during the low-carbohydrate meals, the AUC did not differ compared with the high-carbohydrate occasions (low-carbohydrate: 58.9±18pg/ml/h, high-carbohydrate: 45.2±16pg/ml/h, p=0.028). Hunger sensations were suppressed more after single beverages compared with five small drinks (p=0.009).We found higher EE during 2.5h following one large drink compared with five smaller beverages. Since hunger was also suppressed more efficiently, and serum GLP-1 levels were higher after one compared with five smaller drinks, our findings do not support nibbling to avoid hunger or to keep up EE from morning to noon.