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ESPITE WIDESPREAD CONSENsus that a reduced intake of saturated fat lowers cardiovascular disease (CVD) risk, the optimal type of macronutrient (protein, unsaturated fat, or carbohydrate) that should replace saturated fat is uncertain. In the absence of convincing evidence that favors one macronutrient, reports from the Institute of Medicine 1 and the Adult Treatment Panel III 2 concluded that a wide range of macronutrients is acceptable.Two major goals of dietary recommendations are to lower blood pressure and improve serum lipids, 2 of the primary determinants of CVD risk. A persuasive body of evidence has impli-cated several aspects of diet in the etiology of elevated blood pressure. Early research documented the adverse effects of increased salt, insufficient potassium, elevated weight, and excess alcohol intake, and the beneficial effects of vegetarian dietary patterns. 3,4 Subsequently, in the Dietary Approaches to Stop Hypertension (DASH) trials, 5,6 a carbohydrate-rich diet that emphasizes fruits, vegetables, and low-fat dairy prod-For editorial comment see p 2497.

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The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study.

Context Weight loss elicits physiological adaptations relating to energy intake and expenditure that antagonize ongoing weight loss. Objective To test whether dietary composition affects the physiological adaptations to weight loss, as assessed by resting energy expenditure. Design, Study, and Participants A randomized parallel-design study of 39 overweight or obese young adults aged 18 to 40 years who received an energy-restricted diet, either low-glycemic load or low-fat. Participants were studied in the General Clinical Research Centers of the Brigham and Women's Hospital and the Children's Hospital, Boston, Mass, before and after 10% weight loss. The study was conducted from January 4, 2001, to May 6, 2003. Main Outcome Measures Resting energy expenditure measured in the fasting state by indirect calorimetry, body composition by dual-energy x-ray absorptiometry, cardiovascular disease risk factors, and self-reported hunger. Results Resting energy expenditure decreased less with the low-glycemic load diet than with the low-fat diet, expressed in absolute terms (mean [SE], 96 [24] vs 176 [27] kcal/d; P=.04) or as a proportion (5.9% [1.5%] vs 10.6% [1.7%]; P=.05). Participants receiving the low-glycemic load diet reported less hunger than those receiving the low-fat diet (P=.04). Insulin resistance (P=.01), serum triglycerides (P=.01), C-reactive protein (P=.03), and blood pressure (P=.07 for both systolic and diastolic) improved more with the low-glycemic load diet. Changes in body composition (fat and lean mass) in both groups were very similar (P=.85 and P=.45, respectively). Conclusions Changes in dietary composition within prevailing norms can affect physiological adaptations that defend body weight. Reduction in glycemic load may aid in the prevention or treatment of obesity, cardiovascular disease, and diabetes mellitus.