OBJECTIVES: We investigated the effects of weight loss and maintenance that varied with regard to protein content and glycemic index (GI) on syndrome (MetSyn) status. METHODS: Secondary analyses were performed Diet, Obesity and Genes (DiOGenes) study (2006-2008), a randomized dietary intervention. Nine hundred and thirty-eight overweight and obese from eight European countries entered an 8-wk low-calorie-diet period. hundred and seventy-three adults who lost at least 8% of their body randomized to one of five ad libitum diets for 6 mo: 1) low-protein (LGI); 2) LP/high-GI (HGI); 3) high-protein (HP)/LGI; 4) HP/HGI; and 5) diet. MetSyn prevalence and a standardized MetSyn score were assessed at baseline, after the low-calorie diet, and after the intervention. loss among participants while on the low-calorie diet significantly MetSyn prevalence (33.9% versus 15.9%; P < 0.001) and MetSyn score (- -4.45; P < 0.001). During weight maintenance, significant changes in were observed between the groups, with the highest increase detected in LP/HGI group (P = 0.039, partial eta2 = 0.023). Protein, GI, and their interaction did not have isolated effects on study outcomes. protein nor GI affected MetSyn status in this sample of European obese adults. However, a diet with a combination of an increased protein-to-carbohydrate ratio with low-GI foods had beneficial effects factors.