Substitution of 9.5-9.6%TE dietary SFAs with either MUFAs or n-6 PUFAs did not significantly affect the percentage of flow-mediated dilatation or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure, and E-selectin offer a potential public health strategy for CVD risk reduction. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Replacement of 9.5-9.6%TE dietary SFAs with MUFAs increased EPC numbers, and replacement with either MUFAs or n-6 PUFAs decreased microparticle numbers, suggesting beneficial effects on endothelial repair and maintenance. Further studies are warranted to determine the mechanisms underlying the favorable effects on EPC and microparticle numbers after SFA replacement. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Endothelial dysfunction, combined with inflammation, plays a significant role in the development of atherosclerosis and risk of cardiovascular disease (CVD) (1) . Reduction in dietary saturated fatty acid (SFA) intake is a key dietary recommendation for CVD risk reduction (2) . However, it remains unclear whether monounsaturated fatty acids (MUFA) or n-6 polyunsaturated fatty acids (n-6 PUFA) are the optimal fatty acids to replace dietary SFA. The aim of this study was to determine the effects of substitution of SFA with either MUFA or n-6 PUFA on circulating markers of endothelial function and inflammation in men and women at increased risk of developing CVD.A total of 195 men and women at increased CVD risk (mean age 44 (sd 10) years and BMI 26.9 (SD 4.0) kg/m 2 ) participated in a 16-week, parallel, randomised, controlled, single-blinded intervention study (DIVAS -(Dietary Intervention and VAscular function Study; ClinicalTrials.gov NCT01478958). Participants were randomly assigned (minimised for gender, age, BMI and CVD risk score) to one of the following isoenergetic diets: SFA-rich (target composition: 36 % of total energy (%E) as total fat, 17 %E SFA, 11 %E MUFA, 4%E n-6 PUFA), MUFA-rich (36% E total fat, 9 %E SFA, 19 %E MUFA, 4 %E n-6 PUFA), or n-6 PUFA-rich (36% E total fat, 9%E SFA, 13 %E MUFA, 10 %E n-6 PUFA). A flexible dietary model was developed to deliver the dietary interventions in which exchangeable fats in the habitual diet were replaced by study foods (spreads, oils, snacks) with a specific fatty acid composition. Vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), E-Selectin, P-Selectin, von Willebrand factor (vWf) and C-Reactive protein (CRP) were determined by immunoassays in the fasting blood samples collected at baseline and following 16 weeks of intervention.Blood E-Selectin levels (P = 0.025) were significantly influenced by dietary fat composition. It was observed that there was a differential response after the MUFA-rich compared with the SFA-rich diet in which E-Selectin levels decreased after MUFA (Week16-Week0: -2.33 (SEM 0.91) ng/ml) compared to the increase following the SFA-rich diet (Week16-Week0: 1.27 (SEM 1.01) ng/ml), (P = 0.008). There were no significant effects of treatment on blood VCAM-1, ICAM-1, IL-6, TNF-a, P-Selectin, vWf and CRP.In conclusion, this study suggests that replacement of dietary SFA with MUFA may have beneficial effects on circulating levels of E-Selectin.