Context: Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. Objective: To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. Design, Setting, and Participants: Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. Interventions: A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. Main Outcome Measures: Systolic blood pressure and low-density lipoprotein cholesterol. Results: Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P=.002) and by 3.5 mm Hg (P=.006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P=.01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P=.02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P=.005) and by 2.9 mm Hg among those with hypertension (P=.02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P=.03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P=.02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. Conclusion: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT00051350.
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