Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk

The benefits of dietary phytosterols (PhySs) and long-chain n-3 PUFA (ω3) have been linked to their effects as cholesterol- and triglyceride (TGL)-lowering agents. However, it remains unknown whether these compounds have further metabolic effects on LDL lipid composition. Here, we studied the effects of PhyS- or ω3-supplemented low-fat milk (milk) on the LDL-lipidome. Overweight and moderately hypercholesterolemic subjects (n = 32) were enrolled in a two-arm longitudinal crossover study. Milk (250 ml/day), enriched with either 1.57 g PhyS or 375 mg ω3 (EPA + DHA), was given to the participants during two sequential 28 day intervention periods. Compared with baseline, PhyS-milk induced a higher reduction in the LDL cholesterol (LDLc) level than ω3-milk. LDL resistance to oxidation was significantly increased after intervention with PhyS-milk. Changes in TGL and VLDL cholesterol were only evident after ω3-milk intake. Lipidomic analysis revealed a differential effect of the PhyS- and ω3-milk interventions on the LDL lipid metabolite pattern. Content in LDL-glycerophospholipids was reduced after PhyS-milk intake, with major changes in phosphatidylcholine (PC) and phosphatidylserine subclasses, whereas ω3-milk induced significant changes in the long-chain polyunsaturated cholesteryl esters and in the ratio PC36:5/lysoPC16:0, associated to a reduced inflammatory activity. In conclusion, daily intake of milk products containing PhyS or ω3 supplements induce changes in the LDL-lipidome that indicate reduced inflammatory and atherogenic effects, beyond their LDLc- and TGL-lowering effects.