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Abstract: The objective was to evaluate the metabolic and vascular effects of lifestyle interventions involving a healthy diet and either a moderate- or a high-intensity exercise regimen in nondiabetic subjects with metabolic syndrome. The effects of these interventions on flow-mediated vasodilation (FMD) and risk profiles were compared with a standard low-fat diet and engaging in daily walking (standard of care). Seventy-five healthy adults with metabolic syndrome (30-55 years old) were randomized to a 10 000-steps-a-day exercise program, a 3-times-a-week fitness (>75% peak VO2) program, or a 1-hour-walking-a-day program for 12 weeks. The first 2 interventions were combined with an accessible healthy, no-sugar diet; and the third was combined with a tailored low-fat diet. The outcomes, including FMD and risk factors, were examined at 12 weeks and at 1-year reassessment. Significant increase in FMD (mean difference = 1.51%, 95% confidence interval = 1.05%-3.017%, P = .0007) and decrease in arterial pressure (mean difference = 19.3 ± 2.3/−12.6 ± 1.8 mm Hg, P = .0001) were observed in all groups. However, the FMD changed most favorably in the high-intensity, low-sugar group (mean difference = 1.56%, 95% confidence interval = 0.1%-3.02%, P = .036). Significant improvements in body mass index, waist, insulin-like growth factor–1, homeostasis model assessment of insulin resistance, insulin, glucose, urinary albumin excretion, and lipid profiles occurred in all groups. Metabolic syndrome was resolved in 64%. One year later, weight loss (−9.1 ± 2.3 kg, P = .0001) and arterial pressure decrease (−18.5 ± 2.3/−12.3 ± 2.1 mm Hg, P = .0001) were maintained. Practical, health-centered diet combined with high-intensity exercise is associated with enhanced vascular protection. These data suggest that more intense exercise combined with a low-sugar diet modulates endothelium-dependent vasodilation. [Copyright &y& Elsevier]