Dietary?3 Fatty Acids and Phytosterols in the Modulation of the HDL Lipidome: A Longitudinal Crossover Clinical Study

High-density lipoproteins (HDLs) are complex particles composed of a wide range of lipids, proteins, hormones and vitamins that confer to the HDL particles multiple cardiovascular protective properties, mainly against the development of atherosclerosis. Among other factors, the HDL lipidome is affected by diet. We hypothesized that diet supplementation with ?3 (docosahexaenoic acid: DHA and eicosapentaenoic acid: EPA) and phytosterols (PhyS) would improve the HDL lipid profile. Overweight subjects (n = 20) were enrolled in a two-arm longitudinal crossover study. Milk (250 mL/day), supplemented with either ?3 (EPA + DHA, 375 mg) or PhyS (1.6 g), was administered to the volunteers over two consecutive 28-day intervention periods, followed by HDL lipidomic analysis. The comprehensive lipid pattern revealed that the HDL lipidome is diet-dependent. ?3-milk supplementation produced more changes than PhyS, mainly in cholesteryl esters (CEs). After ?3-milk intake, levels of DHA and EPA within phosphatylcholines, triglycerides and CE lipids in HDLs increased (p < 0.05). The correlation between lipid species showed that lipid changes occur in a coordinated manner. Finally, our analysis revealed that the HDL lipidome is also sex-dependent. The HDL lipidome is affected by diet and sex, and the 4 weeks of ?3 supplementation induced HDL enrichment with EPA and DHA.

Automated summary

High-density lipoproteins (HDLs) are complex particles that have multiple cardiovascular protective properties. Diet, specifically supplementation with ?3 and phytosterols, has been shown to improve the lipid profile of HDL. This study found that ?3 supplementation had greater effects on HDL lipidome compared to phytosterols, particularly in cholesteryl esters (CEs). Furthermore, the HDL lipidome was found to be sex-dependent. Overall, this study highlights the importance of diet and sex in modulating the HDL lipid profile.