Dairy Attenuation of Metabolic Disease

Dairy Attenuation of Oxidative and Inflammatory Stress in Metabolic Syndrome

Forty overweight and obese subjects (BMI 25-39.9) with metabolic syndrome will be randomized to inadequate dairy (<0.5 serving/day) and adequate dairy (3.5 servings/day) weight maintenance (eucaloric) diets for 12 weeks. Body weight will be measured weekly and body composition (via dual X-ray absorptiometry), insulin sensitivity index, plasma lipids and calcitrophic hormones will be measured at weeks 0, 4 and 12 of the dietary intervention. Oxidative burden will be assessed by measurement of plasma malonaldehyde, 8-isoprostane F2α and oxidized LDL 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 0, 1, 4 and 12 weeks). An additional global evaluation of diet-induced changes in cytokines will be conducted using cytokine protein arrays to profile relative changes in 36 additional potentially relevant cytokines. All data will be analyzed via two-factor (diet X obesity status) multivariate analysis of variance (MANOVA)

Study Overview

• Status: Completed
• Conditions: Inflammation; Oxidative Stress
• Intervention / Treatment: Dietary supplement: Low Dairy; Dietary supplement: Adequate Dairy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37996
      • The University of Tennessee Nutrition and Metabolic Research Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Diagnosis of metabolic syndrome as defined by NCEP ATP III criteria: Presence of three or more of the following risk determinants:

  • Abdominal obesity (This criterion must be met by all obese subjects entered into the study)

    • Waist circumference >102 cm for males
    • Waist circumference >88 cm for females
  • Triglycerides >150 mg/dL
  • HDL cholesterol <40 mg/dL (men); < 50 mg/dL (women)
  • Blood pressure >130/>85 mm Hg (This criterion must be met by all subjects [overweight and obese] entered into the study).

  • Fasting glucose >100 mg/dL

    • Body mass index (BMI) 25-39.9
    • Age 18-50 years
    • Weight stable: no more than 1 kg weight gain or loss during past four weeks

Exclusion Criteria:

• • BMI < 25 or >40

  • Type II diabetes requiring the use of any oral antidiabetic agent and/or insulin (because of confounding effects on ROS)
  • Adverse response to study foods (lactose intolerance, dairy intolerance, dairy allergy); this will be determined by self-report.
  • history or presence of significant metabolic disease which could impact on the results of the study (i.e. endocrine, hepatic, renal disease)
  • history of eating disorder
  • presence of active gastrointestinal disorders such as malabsorption syndromes
  • pregnancy or lactation
  • use of obesity pharmacotherapeutic agents within the last 6 months
  • use of over-the-counter anti-obesity agents (e.g. those containing phenylpropanalamine, ephedrine and/or caffeine) within the last 3 months
  • Chronic use of anti-inflammatory agents within the last four weeks
  • Use of antioxidant supplements within the last four weeks
  • Recent (current or past 12 weeks) use of any psychotropic medication
  • Recent (past four weeks) initiation of an exercise program
  • Recent (past twelve weeks) initiation of hormone replacement therapy or change in HRT regimen
  • Recent (past twelve weeks) initiation of hormonal birth control or change in hormonal birth control regimen
  • Recent (past 12-weeks) history of tobacco use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low Dairy; <0.5 standard dairy servings/day	Dietary supplement: Low Dairy; Less than 0.5 standard servings of dairy products per day
Experimental: Adequate dairy; 3.5 standard dairy servings per day	Dietary supplement: Adequate Dairy; 3.5 standard servings of dairy foods per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight		12 weeks
Body composition	DEXA assessment	12 weeks
Oxidative Stress	plasma malonaldehyde, 8-isoprostane F2α and oxidized LDL	12 weeks
Inflammatory stress	Plasma L-6, IL-15, MCP, C-reactive protein, adiponectin and TNF-α	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure		12 weeks
Lipids		12 weeks
Insulin sensitivituy	Glucose, insulin and HOMA	12 weeks

Collaborators and Investigators

• Sponsor: University of Tennessee
• Investigators: Principal Investigator: Michael B. Zemel, Ph.D., The University of Tennessee

Publications and helpful links

General Publications

• Stancliffe RA, Thorpe T, Zemel MB. Dairy attentuates oxidative and inflammatory stress in metabolic syndrome. Am J Clin Nutr. 2011 Aug;94(2):422-30. doi: 10.3945/ajcn.111.013342. Epub 2011 Jun 29.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: December 22, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (Estimate): December 24, 2010

Study Record Updates

• Last Update Posted (Estimate): December 24, 2010
• Last Update Submitted That Met QC Criteria: December 22, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: inflammation; body composition; oxidative stress; dairy; reactive oxygen species
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: R011770040