Dairy Attenuation of Oxidative and Inflammatory Stress in Metabolic Syndrome

This study is designed to determine the effects of a dairy-rich diet on oxidative and inflammatory stress in metabolic syndrome patients in the presence and absence of obesity. Forty overweight and obese subjects (BMI 25-39.9) with metabolic syndrome as defined by NCEP ATP III criteria will be randomized to inadequate (0-0.5 daily serving) or adequate (3.5 servings) dairy diets in the presence of a eucaloric weight maintenance diet for 12 weeks. All subjects will undergo a 14-day lead-in period to establish a stable baseline of dietary and physiological measures (described below), followed by the 12-week intervention period. Baseline dietary assessments will be conducted by the project dietitian during the two-week lead-in period which will be used to provide an initial estimate of a maintenance level of caloric intake. This will be refined by calculating energy needs using DRI equations for calculation of age- and physical activity (PA) adjusted total energy expenditure (TEE) for men and women. Energy requirements will be confirmed via measurement of resting metabolic rate via indirect calorimetry.

Subjects will be given diets isocaloric to those consumed during the lead-in period, with macronutrient and fiber levels maintained equivalent at levels approximating the estimated U.S. average (described in Diets section). Subjects on the inadequate dairy diets will be assigned diets containing < 600 mg Ca/day and <0.5 daily serving of dairy foods, and subjects on the adequate dairy diets will be assigned diets containing 1200 - 1400 mg Ca/day and 3.5 daily servings of dairy (milk, yogurt, hard cheese). Two of the three dairy servings consumed daily by those on the high dairy diet will be milk and/or yogurt to ensure sufficient consumption of whey proteins. All subjects will be provided individual instruction, counseling and assessment from the study dietitian regarding dietary adherence and the development and reinforcement of strategies for continued success, and diets will be monitored weekly. Physical activity will be assessed using pedometer counts and maintained at approximately pre-study levels throughout the study. Pedometer counts will be recorded daily for the 14-day lead-in period and the value averaged to provide a pre-study baseline. Subjects will be asked to maintain the same level of activity (plus or minus 500 steps/day) and will use pedometers for self-assessment. Pedometer counts will be recorded and provided to the study staff on a weekly basis, along with the diet records.

Body weight, waist circumference, and blood pressure will be measured weekly and body composition (via dual X-ray absorptiometry) will be measured at weeks 0, 4 and 12 of the dietary intervention. Resting metabolic rate and respiratory quotient will be assessed at weeks 0 and 12. Oxidative burden will be assessed by measurement of plasma malonaldehyde, 8-isoprostane F2α and oxidized LDL at weeks 0, 1, 4 and 12, and inflammatory stress will be assessed by measurement of IL-6, IL-15, MCP, C-reactive protein, adiponectin and TNF-α levels in plasma at the same time intervals. Glucose tolerance, HOMAIR, fasting plasma lipids, PTH and 1,25-(OH)2-D levels will be determined at the same time intervals (0, 4, and 12 weeks). All data will be analyzed via two-factor multivariate analysis of variance (MANOVA).