Impact of saturated fat absorption on serum low density lipoprotein-cholesterol response to the replacement of saturated with unsaturated fats in healthy males. The 'Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-2 (RISSCI-2)' non-randomised sequential dietary intervention study.

BACKGROUND AND AIMS: Serum low-density lipoprotein (LDL)-cholesterol varies in response to the isonergetic replacement of saturated (SFA) with unsaturated fats (UFA), as reported in our previous screening study, 'Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1' (RISSCI-1). In the present study, we aimed to determine if differences in postprandial absorption and metabolic handling of SFA could explain variability in responsiveness of serum LDL-cholesterol to dietary SFA intake. METHODS: Male participants classified according to their fasting LDL-cholesterol response to the replacement of SFA with UFA in our screening study (RISSCI-1) as higher (HR, n = 19) or lower responders (LR, n = 17), were placed on two, 4-week isoenergetic diets (higher-SFA/lower-UFA followed by lower-SFA/higher-UFA). After each diet, [U-13C]palmitic acid was given in the first of two sequential meals to trace postprandial saturated fat absorption. RESULTS: Repeating the previous dietary regime in the same participants resulted in similar inter-individual variation in LDL-cholesterol response, with greater reductions in lipid ratios (total cholesterol:high density lipoprotein (HDL) and LDL-cholesterol:HDL-cholesterol) and largest LDL-1-subfraction in the HR versus the LR group (p < 0.0001 for all). There was no difference in the absorption of SFA between groups but a significantly greater recovery of [U-13C]palmitic acid-triacylglycerol in the postprandial period in LR relative to the HR group after SFA replacement with UFA was observed (p = 0.019). CONCLUSIONS: Dietary SFA absorption did not explain individual variation in serum LDL-cholesterol response to SFA replacement with UFA. Exploratory findings of a difference in postprandial [U-13C]palmitic acid-triacylglycerol warrants further investigation.