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.