The traditional Mediterranean diet (MedDiet) is now widely recommended in the prevention of CVD. However, it is not known whether the MedDiet has the same beneficial cardiovascular effects in women and in men. The objective of the present study was to investigate sex-related differences with regard to changes in cardiometabolic variables in response to a 4-week isoenergetic MedDiet. Participants were thirty-eight men and thirty-two premenopausal women aged between 25 and 50 years who had slightly elevated LDL-cholesterol (LDL-C) concentrations (3·4–4·9 mmol/l) or total cholesterol:HDL-cholesterol ratio ≥ 5·0. A 4-week run-in period preceded the MedDiet in order to control the inter- and intra-individual variability. Cardiometabolic variables were measured before and after the MedDiet. Total cholesterol, LDL-C, apoB and apoA-1 plasma concentrations as well as diastolic blood pressure decreased (
P< 0·05) in both men and women (respectively, 10, 10, 10, 6 and 5 % for men and 6, 7, 9, 4 and 4 % for women). ApoA-2 concentrations and insulin concentrations 2 h after the oral administration of 75 g of glucose demonstrated sex × time interactions (respectively, P= 0·05 and P= 0·03) and only men experienced a decrease for these variables (respectively, 8 and 25 %). In conclusion, consuming a MedDiet led to significant changes in plasma lipid profile in both men and women, while only men had significant improvements in insulin homeostasis. These results support the importance of investigating sex-related differences in response to diet in order to perhaps further individualise dietary guidelines in the prevention of CVD and type 2 diabetes.