Background: Weight loss reduces body fat and lean mass, but whether these changes are influenced by macronutrient composition of the diet is unclear. 20% fat ( 0.34), or 65% and 35% carbohydrate ( 0.27). Participants lost 2.3 0.2 kg (13.8%) abdominal fat: 1.5 0.2 kg (13.6%) subcutaneous fat and 0.9 0.1 kg (16.1%) visceral fat (all < 0.0001 compared with baseline values), with no differences between the diets ( 0.29). Women lost more visceral fat than did men relative to total-body fat loss. Participants regained 40% of these losses by 2 y, with no differences between diets ( 0.23). Weight loss reduced hepatic fat, but there were no differences between groups ( 0.28). Dietary goals were not fully met; self-reported contrasts were closer to 2% protein, 8% fat, and 14% carbohydrate at 6 mo and 1%, 7%, and 10%, buy EGFR Inhibitor respectively, at 2 y. Conclusion: Participants lost more fat than lean mass after consumption of all diets, PR52B with no differences in changes in body composition, abdominal fat, or hepatic fat between assigned macronutrient amounts. This trial was registered at clinicaltrials.gov as NCT00072995. See corresponding editorial on page 535. INTRODUCTION Many trials of dietary approaches to weight loss report primarily changes in total body weight and waist circumference because these are easily obtained proxy measures of total fat mass and abdominal fat. However the primary aim buy EGFR Inhibitor of any weight loss regimen is the reduction of fat mass rather than lean mass, and the measurement of total body weight change does not provide detailed information about relative changes in fat and lean mass. Although studies have examined body-composition changes in response to energy-reduced diets (1), exercise (2), or both (3, 4), only a few studies have directly compared changes in fat mass and lean mass in 2 calorie-reduced diets that varied in macronutrient composition (5C8). In some studies (9C13), but not in others (14, 15), low-carbohydrate, high-protein diets resulted in preferential loss of fat and preservation of lean mass. Visceral fat mass is closely related to the metabolic consequences of obesity (16C20), and excess visceral fat is commonly thought to release fatty acids into the portal vein, which leads to an accumulation of fat in the liver (hepatic fat). Few trials have directly measured changes in visceral or hepatic fat in response to weight-reducing diets (3, 21C24), and there remains debate about which, if any, diet or diets are most effective for visceral fat loss, with very sparse data on dietary treatments to reduce hepatic fat accumulation (23C25). Some studies have shown higher-protein, low-carbohydrate diets (11, 21, 26) or pharmacologic weight-loss approaches (27) to result in greater visceral fat loss than have conventional energy-restricted diets. Smith and Zachweija (28) reviewed 23 studies that involved 599 participants and showed that several approaches to weight loss (eg, caloric restriction, pharmaceutical brokers, bariatric surgery, or exercise) preferentially reduced visceral fat, and individuals lost more visceral fat if they carried higher amounts of total body fat at baseline. Hallgreen and Hall (29) used an allometric equation, which has traditionally been used to describe the growth of a body part as a function of total body size, to quantify the relation between changes in visceral fat and total fat during intentional weight loss. In their model, the change in visceral fat relative to the change in total-body fat mass was expressed as a function of the baseline ratio of visceral fat to fat mass. The authors (29) reported that changes in visceral fat mass were allometrically related to changes in fat mass during weight loss, regardless of sex or the approach used for weight loss. The POUNDS LOST4 trial (www.clinicaltrials.gov; NCT00072995) was a 2-center study that examined changes in body composition over buy EGFR Inhibitor 2 y in a large group of men and women who ate 1 of.