Background: Although lifestyle modification is the key treatment of metabolic syndrome (MetS), clinical data on the dynamical relationship between metabolic state and MetS has been limited. This study investigated the mutual correlations between demographic and biochemical variables, and the metabolic state based on the plasma amino acid (AA) concentrations, during a lifestyle modification for MetS. Methods and Results: Japanese subjects, consisting of 54 patients with MetS [MetS(+)] and 35 persons without MetS [MetS(-)] were included in the study. Before a lifestyle modification program, the levels of glutamate metabolism-related AA (Glu-mAA), aromatic AA metabolism-related AA (Aromatic-mAA) and alanine metabolism-related AA (Ala-mAA) were significantly higher, while those of glycine-serine-threonine metabolism-related AA (Gly-Ser-Thr-mAA) were significantly lower compared to those in MetS(-). After a lifestyle modification, significant reductions (P<0.05) in the BMI (-1.4 kg/m²), mean blood pressure (-7.9 mmHg), hemoglobin A_1c (-0.4%), and triglycerides (-30.6 mg/dl) were observed, and significant differences in the plasma AA levels between MetS(+) and MetS(-) were resolved. In addition, the diagnostic items of MetS were positively correlated with the levels of Glu-mAA, Ala-mAA, branched chain AA (BCAA)-mAA, Aromatic-mAA, and negatively correlated with the levels of Gly-Ser-Thr-mAA. Conclusions: As MetS subsided, the abnormality of mean plasma AA levels of the MetS(+) group returned to similar values as those in the MetS(-) group, suggesting a novel viewpoint regarding the metabolic mechanism of lifestyle modification. (Circ J 2010; 74: 2434-2440)