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

J Lipid Res. 2015 May;56(5):1043-56. doi: 10.1194/jlr.P052217. Epub 2015 Mar 15.

Abstract

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.

Keywords: atherosclerosis; cholesterol; diet and dietary lipids; glycerophospholipids; low density lipoprotein-lipid metabolites; mass spectrometry; phospholipids; triglycerides.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Animals
  • Cholesterol / blood
  • Cross-Over Studies
  • Double-Blind Method
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Lipid Metabolism / drug effects
  • Lipoproteins, LDL / blood*
  • Lipoproteins, LDL / chemistry
  • Male
  • Middle Aged
  • Milk
  • Overweight / blood*
  • Oxidation-Reduction
  • Particle Size
  • Phytosterols / administration & dosage*
  • Treatment Outcome

Substances

  • Fatty Acids, Omega-3
  • Lipoproteins, LDL
  • Phytosterols
  • Cholesterol