Fatty acid composition of isoenergetic meals drives distinct postprandial immunometabolic responses in healthy adults: A randomized crossover pilot study

The postprandial period represents a critical and dynamic phase during which dietary components can acutely influence metabolic and immune functions. While the chronic effects of dietary fat quality are well characterized, their immediate postprandial immunometabolic impact remains poorly understood. To investigate the acute effects of energy-matched test meals enriched in saturated (SFA), monounsaturated (MUFA), or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFA), compared to a fat-free control, on systemic metabolic and immune parameters in healthy adults. In this randomized, crossover pilot study, ten healthy participants consumed four test meals separated by 2-week washouts. Blood samples were collected at fasting, 2-3 h (peak), and 5-6 h (late phase) postprandially. Biochemical and immunological biomarkers were assessed. Statistical analyses included two-way repeated-measures ANOVA, linear mixed models, and area under the curve (AUC/iAUC) calculations. MUFA- and ω3-LCPUFA-enriched meals induced significantly greater postprandial changes in glucose, triacylglycerides, LDL-C, and C-peptide compared to the SFA and fat-free meals, particularly at the late postprandial phase. These effects were confirmed by AUC and iAUC analyses. In contrast, although transient changes in immune cell counts and humoral markers were observed over time, no significant differences between fat types were detected in postprandial immune responses. In healthy adults, the fatty acid composition of energy-matched meals acutely modulates key metabolic pathways in a fat-type-specific manner, whereas systemic immune parameters remain largely unchanged. These preliminary findings suggest a functional dissociation between postprandial metabolic and immune response and underscore the need to more sensitive or compartment-specific immune readouts in future nutritional research.