The rise in the prevalence of obesity and type 2 diabetes mellitus has been linked to an increased consumption of sugar- and particularly fructose-sweetened beverages. Preliminary evidence suggests that this could be partly explained by the fact that the reduction in the intake of solid food is inadequate to compensate for additional energy taken up from these beverages. In addition, the type of sugar used to sweeten a beverage might have a considerable impact on the body's ability to adjust food intake properly. In particular, the consumption of fructose has been reported to reduce diurnal plasma glucose, insulin, and leptin concentrations, but increase diurnal ghrelin concentrations as compared to isocaloric amounts of glucose. As the plasma concentrations of glucose, insulin, leptin, and ghrelin are involved in the regulation of food intake and energy expenditure, this might impair the longer-term ability of the body to match food intake and energy expenditure to stabilize body weight.

To investigate whether the regular consumption of fructose-sweetened beverages leads to an increase in total energy intake, the investigators will enroll healthy normal-weight subjects into a controlled diet study using a double-blind randomized cross-over design. Each subject will complete three diet periods: solid food plus a beverage sweetened with fructose (A), solid food plus a beverage sweetened with glucose (B), solid food plus a beverage sweetened with a non-caloric sweetener (C). During each period, subjects will be provided with all their food for 8 days. These diets will consist of meals freshly prepared using regular food items typically found in the American diet. Solid food will be provided in excess of what the subjects are estimated to require. Subjects will be asked to eat as much of this food as they need to feel comfortably satiated, and to return all excess foods to the Nutrition Research Kitchen of the University of Washington (UW) General Clinical Research Center (GCRC). This returned food will be weighed to assess precisely the amount and type of food eaten by the subjects on each day of these diet periods. In addition to this solid food, subjects will be asked to drink a certain amount of a lemonade sweetened with either fructose (A), glucose (B), or a non-caloric sweetener (C). In groups A and B, the subjects will consume 25% of their estimated daily calorie requirement in the form of these sugar sweetened beverages, while the drink in period C will be of the same volume.

Subjects will be admitted to the GCRC on the morning of day 9 of each diet period for the measurement of resting metabolic rate by means of indirect calorimetry and blood draws for the measurement of fasting plasma concentrations of adipogenic hormones and plasma lipids. Furthermore, we will administer a standardized breakfast and draw blood before and 0, 15, 30, 60, 90, and 120 minutes after this meal to measure the postprandial plasma concentrations of insulin, ghrelin, and satiety signals. Following the last postprandial blood draw, we will serve another meal to measure ad libitum food intake. Our hypothesis is that subjects will have more appetite and consume more food after they have consumed the fructose-sweetened beverage for 8 days.

Primary outcome measures of this study will be the total energy consumed during the periods A, B, and C; the reduction in the intake of solid foods in periods A and B as compared to period C; and energy uptake during the ad libitum meal served on day 9 of each diet period. Secondary outcome measures will be resting energy expenditure and plasma concentrations of satiety and adiposity signals.