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.