Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance.

Background: Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. Methods: We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. Results: A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein-high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein-high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events. Conclusions: In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss. (Funded by the European Commission; ClinicalTrials.gov number, NCT00390637.) N Engl J Med 2010;363:2102-13.