Pre-Menopausal Women, Classified as Hypo- or Hyper-Responders, do not Alter their LDL/HDL Ratio Following a High Dietary Cholesterol Challenge

Background: Cholesterol is the dietary component that has elicited the most public interest in conjunction with coronary heart disease. However, the impact of excess dietary cholesterol intake on plasma cholesterol levels cannot be accurately predicted; therefore, its role in disease progression is not straightforward. Individual response variation can be due to factors such as ethnicity, hormonal status, obesity and genetic predisposition. Objective: The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic pre-menopausal women, classified based on their response to a high dietary cholesterol challenge. Design: We recruited 51 pre-menopausal women (29 Caucasian and 22 of Hispanic origin) aged 18 to 49 years with initial plasma cholesterol concentrations ranging from 3.62 to 5.17 mmol/L. Using a cross-over research design, women were randomly allocated to an egg (640 mg additional dietary cholesterol per day) or placebo group (0 mg additional dietary cholesterol per day) initially, and the two 30 day periods were separated by a three-week washout. Results: An initial evaluation of the ethnicity effects revealed elevations in both plasma LDL-C (p < 0.0001) and HDL-C (p < 0.001) concentrations in both Hispanics and Caucasians during the high dietary cholesterol period. However, these increases were not accompanied by a change in the LDL/HDL ratio. Subjects were then classified as hypo- (< 0.05 mmol/L increase in total plasma cholesterol per each additional 100 mg of dietary cholesterol consumed per day) or hyper-responders (≥0.06 mmol/L increase in total blood cholesterol per each additional 100 mg of dietary cholesterol consumed per day), based on their reaction to the additional dietary cholesterol provided. Hypo-responders did not experience an increase in LDL-C or HDL-C during the egg period, while both lipoproteins were elevated in hyper-responders. However, the LDL/HDL ratio, an important parameter of coronary heart disease risk, was maintained for all subjects during the egg period independent of response. Furthermore, hyper-responders had higher concentrations of apo C-III (p < 0.001), apo B (p < 0.001) and cholesterol ester transfer protein (CETP) (p < 0.05) during this period. Conclusion: These data revealed that excess dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in pre-menopausal women, regardless of their response classification. Although the addition of 640 mg of cholesterol to the diet did result in an increase in plasma cholesterol in hyper-responders, the LDL/HDL ratio was maintained. This result, accompanied by increases in CETP activity, leads to the speculation that hyper-responders may process the excess cholesterol in the plasma compartment through an enhancement of the reverse cholesterol transport pathway. With this mechanism identified, further measurement of additional parameters is needed to verify this conclusion.