Introduction
Brain-derived neurotropic factor (BDNF) contributes to cognition and metabolism. Dietary factors have an effect on fasting BDNF concentrations, which could be mediated by insulin and/or glucose.

Objectives
Insulin and glucose responses are different for each macronutrient. Therefore, we investigated the postprandial effects of the macronutrients fat, carbohydrates, or protein on BDNF concentrations in order to distinguish the role between insulin and glucose. Both serum and plasma BDNF was analyzed, because concentrations differ depending on the matrix.

Methods
Healthy overweight/obese male subjects (n=18) completed three test days with 1 week wash-out in a randomized, double-blind fashion. They had to consume a high-fat (En% fat, carbohydrates, protein: 52.3, 39.2, 8.0), high-carbohydrate (En% 9.6, 81.5, 8.6) or high-protein shake (En% 10.6, 51.5, 36.9). BDNF concentrations were measured after 0, 60, and 240 min. Glucose and insulin concentrations were measured after 0, 15, 30, 45, 60, 90, 120, and 240 min.

Results
Serum BDNF concentrations were higher than in plasma (P<0.001). Serum BDNF concentrations significantly decreased after the high-fat (P=0.013) and high-carbohydrate shakes (P=0.040), and showed a trend after the high-protein shake (P=0.076). There were no differences between shakes (P=0.66). There were no significant changes in plasma BDNF concentrations after the different shakes (P=0.47). Total area under the curve (AUC) for glucose after the high-carbohydrate shake was significantly higher than the high-fat (P=0.003) and high-protein shakes (P<0.001), and the total AUC for insulin was higher after the high-carbohydrate (P<0.001) and high-protein shakes (P<0.001) than the high-fat shake. Therefore, acute glucose and insulin changes do not seem to affect postprandial BDNF concentrations.

Conclusions
BDNF concentrations were higher in serum than in plasma. No differences were found in postprandial BDNF concentrations between shakes, so insulin or glucose do not contribute to the regulation of postprandial BDNF concentrations.