Low-density lipoprotein cholesterol responsiveness to diet in normolipidemic subjects

Both apolipoprotein E genotype (apo E) and diet predict very-low-density (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. In a retrospective pooled analysis of six studies, we sought to identify the predictors of VLDL-C and LDL-C change, or "responsiveness," to a diet crossover. "Response" to diet was studied in 67 normolipidemic subjects of common apo E genotype. Subjects were fed two contrasting, metabolically controlled diets: one had a low polyunsaturated to saturated fatty acid ratio (P:S), and the other had a high P:S ratio. Multiple blood samples were analyzed for VLDL-C and LDL-C levels at the end of each metabolic diet period, and values were averaged and differences were calculated. Despite adjustment for significant predictors across the component studies, a wide range of LDL-C responsiveness was found, with an average decrease of 28 mg/dL. Multivariate regression analysis was used to identify the most significant predictors of LDL-C response to the diet crossover. All dietary and clinical variables were entered by stepwise regression for potential inclusion in a "best-fit" model. The degree of change in saturated fat content and age were the most significant predictors of LDL-C responsiveness. Neither dietary cholesterol nor apo E phenotype were significant predictors of responsiveness. The most LDL-C-responsive subjects were older and required smaller reductions in dietary saturated fat levels than did less-responsive subjects to achieve a comparable reduction in LDL-C levels. Multiple regression analysis suggested a precursor-product relationship between VLDL-C and LDL-C responsiveness.