Aim: Our objective was to assess alterations in metabolic risk factors, body weight, fat mass and hormonal parameters following 6 weeks of lifestyle intervention with increased physical activity and either a meal-replacement regimen or a low calorie diet. Research Methods and Procedures: 90 overweight or obese subjects (age 47 ± 7.5 years, weight 90.6 ± 11.3 kg, BMI 31.5 ± 2.3) were included in this randomized controlled clinical trial. Subjects in the fat-restricted low-calorie-diet group (LCD-G; n = 30) received 2 dietary counseling sessions and instructions on how to increase physical activity. Subjects in the meal-replacement-diet group (MRD-G; n = 60) received the same lifestyle education and were instructed to replace 2 daily meals by a low-calorie high soy-protein drink. Results: Subjects in the MRD-G lost significantly more weight (6.4 vs. 3.1 kg, p < 0.01) and fat mass (5.1 vs. 2.8 kg, p < 0.01) than the LCD-G. Most metabolic risk parameters were reduced in both the MRD-G and the LCD-G; however, subjects in the MRD-G showed a higher reduction in waist circumference (6.1 vs. 1.8 cm, p < 0.01) and a larger decrease in triglycerides (–19.6 vs. +12.5 mg/dl, p < 0.01). The prevalence of the metabolic syndrome was reduced in subjects in the MRD-G only (–12%, p < 0.05) compared to an unchanged risk score in the LCD-G. The reductions in leptin (18.2 vs. 6.97 ng/ml) and insulin (4.92 vs. 0.58 µU/ml) were only significant in the MRD-G (p < 0.01). Discussion: Our data suggest that even over a short period of time, a meal-replacement diet is more effective in reducing metabolic risk factors, insulin, and leptin, and in improving anthropometric measures than a fat-restricted low-calorie diet.

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