Abstract
The dietary recommendation to lower CVD risk by reducing intake of saturated fatty acids (SFA) to decrease atherogenic serum LDL cholesterol (LDL-C), also lowers cardioprotective HDL. Irrespective of how this response affects CVD risk, there is significant inter-individual variation in serum LDL-C response.
The Reading Imperial Surrey Saturated fat Cholesterol Intervention (‘RISSCI-1’) was designed to determine the metabolic and genetic origins of variation in serum LDL-C response to the replacement of SFA in healthy men. In ‘RISSCI-2’, subgroups of high and low LDL-C responders repeated the same dietary intervention and underwent more detailed metabolic investigations. It was hypothesised, that the diet would produce variable reductions in both serum LDL-C and HDL-C, and that this variation could be explained by common metabolic and genetic traits.
In RISSCI-1, replacement of SFA with unsaturated fats decreased serum HDL-C (7.4%, P<0.05), and produced significant reductions in the larger HDL2 subfractions (11% HDL2b, P=0.002, 9% HDL2a, P=0.003). These findings were associated with an increase in serum biomarkers of cholesterol absorption in the gut (10-28%, P<0.001) and decrease in whole body cholesterol synthesis (6%, P = 0.015). Carriage of an apoE4 allele was associated with higher total cholesterol and LDL-C at baseline, but had no significant effect on lipoprotein response to diet. The direction of change in HDL-C concurred with that of LDL-C in 70% of participants, with age, weight, BMI, and triacylglycerol being predictors of LDL-C response. In RISSCI-2, there were significant decreases in all serum lipids, apo-AI and apo B between LDL-C and between responder and non-responder groups. Serum biomarkers of cholesterol absorption in the gut also showed non-significant increases.
In conclusion, these findings provide insight into changes in cholesterol homeostasis that could partly explain variation in the serum lipoprotein response to SFA replacement, and be used to target dietary advice in the future.