Abstract

Introduction: HDL composition is an important determinant of cardioprotective functions. Importantly, sex-specific differences in HDL composition and function have been observed. While diet represents a promising therapeutic strategy to optimize HDL composition and function, it is unclear whether the capacity to modulate HDL profiles through diet is sex-specific. Hypothesis: We hypothesized that daily consumption of different egg-based diets, which differentially impact HDL particle profiles and efflux capacity, would alter HDL composition and function in a sex-dependent manner. Methods: Healthy men and women (n = 26) participated in a 16-week randomized, crossover intervention trial (NCT03577223), in which they consumed a 4-week egg-free diet, followed by a 4-week diet containing either 3 whole eggs or 3 egg whites per day. Participants then followed a 4-week egg-free washout diet, before switching to the alternative whole egg or egg white diet treatment. Fasted blood samples were collected after each diet period to determine HDL particle profiles by NMR, serum paraoxonase 1 (PON1) lactonase activity, cholesterol efflux capacity, and HDL lipid and protein composition. Results: We observed sex-specific differences in HDL profiles following egg intake. In women, whole egg intake increased HDL-phosphatidylcholine and phosphatidylethanolamine content, whereas HDL-phosphatidylinositol and sphingomyelin were increased and decreased, respectively, in men. Similarly, egg diets differentially and sex-dependently altered HDL proteins implicated in cholesterol efflux capacity and cardiovascular disease risk. Whole egg intake increased HDL-apoAII, apoL1, apoM, and lowered serum amyloid P compared to the egg-free and egg white diets in women, whereas HDL-PON3 was increased by egg white intake in men. PON1 activity and cholesterol efflux capacity were increased following whole egg intake in women only. Independent of sex, changes in cholesterol efflux capacity between the egg white and whole egg periods were positively correlated with the number of total and small HDL particles. Conclusions: Modulation of HDL profiles by diet are sex-specific, with whole egg intake promoting more significant changes in HDL composition and function in women.

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