ABSTRACT: BACKGROUND:Current dietary recommendations for cardiovascular disease (CVD) prevention focus more on dietary patterns than on single nutrients. However, randomized controlled trials using whole-diet approaches to study effects on both fasting and postprandial CVD risk markers are limited. OBJECTIVE:This randomized parallel trial compared the effects of a healthy diet (HD) with those of a typical Western diet (WD) on fasting and postprandial CVD risk markers in overweight and obese adults. METHODS:After a 2-wk run-in period, 40 men and women (50-70 y; BMI: 25-35 kg/m2) consumed the HD (high in fruit and vegetables, pulses, fibers, nuts, fatty fish, polyunsaturated fatty acids; low in salt and high-glycemic carbohydrates; n = 19) or the WD (less fruit, vegetables, and fibers; no nuts and fatty fish; and more saturated fatty acids and simple carbohydrates; n = 21) for 6 wk. Fasting and postprandial cardiometabolic risk markers were assessed as secondary outcome parameters during a 5-h mixed-meal challenge, and a per protocol analysis was performed using 1-factor ANCOVA or linear mixed models. RESULTS:Differences in diet-induced changes are expressed relative to the HD group. Changes in fasting plasma total cholesterol (-0.57 ± 0.12 mmol/L, P < 0.001), LDL cholesterol (-0.41 ± 0.12 mmol/L, P < 0.01), apolipoprotein B100 (-0.09 ± 0.03 g/L, P < 0.01), and apolipoprotein A1 (-0.06 ± 0.03 g/L, P = 0.05) were significantly different between the diet groups. Changes in postprandial plasma triacylglycerol (diet × time, P < 0.001) and apolipoprotein B48 (P < 0.01) differed significantly between the groups with clear improvements on the HD, although fasting triacylglycerols (-0.24 ± 0.13 mmol/L, P = 0.06) and apolipoprotein B48 (1.04 ± 0.67 mg/L, P = 0.40) did not. Significant differences between the diets were also detected in fasting systolic (-6.9 ± 3.1 mmHg, P < 0.05) and 24-h systolic (-5.0 ± 1.7 mmHg, P < 0.01) and diastolic (-3.3 ± 1.1 mmHg, P < 0.01) blood pressure. CONCLUSION:A whole-diet approach targeted multiple fasting and postprandial CVD risk markers in overweight and obese adults. In fact, the postprandial measurements provided important additional information to estimate CVD risk. This trial is registered at clinicaltrials.gov as NCT02519127.