Effect of the Mediterranean diet with and without weight loss on surrogate markers of cholesterol homeostasis in men with the metabolic syndrome

The mechanisms implicated in the LDL-cholesterol (LDL-C)-lowering effects of the Mediterranean-type diet (MedDiet) are unknown. The present study assessed the impact of the MedDiet consumed under controlled feeding conditions, with and without weight loss, on surrogate markers of cholesterol absorption, synthesis and clearance using plasma phytosterols, lathosterol and proprotein convertase subtilisin/kexin-9 (PCSK9) concentrations, respectively, in men with the metabolic syndrome. The subjects' diet (n 19, 24-62 years) was first standardised to a baseline North American control diet (5 weeks) followed by a MedDiet (5 weeks), both under weight-maintaining isoenergetic feeding conditions. The participants then underwent a 20-week free-living energy restriction period (10 (SD 3)% reduction in body weight, P<0.01), followed by the consumption of the MedDiet (5 weeks) under controlled isoenergetic feeding conditions. The LDL-C-lowering effect of the MedDiet in the absence of weight loss (-9.9%) was accompanied by significant reductions in plasma PCSK9 concentrations (-11.7 %, P<0.01) and in the phytosterol: cholesterol ratio (-9.7%, P<0.01) compared with the control diet. The addition of weight loss to the MedDiet had no further impact on plasma LDL-C concentrations and on these surrogate markers of LDL clearance and cholesterol absorption. The present results suggest that the MedDiet reduces plasma LDL-C concentrations primarily by increasing LDL clearance and reducing cholesterol absorption, with no synergistic effect of body weight loss in this process.