Dairy Foods and Weight Loss

Study Overview
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Brief Summary
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Obesity is a national epidemic with multiple causes and complex solutions. Research in both animals and humans has suggested that the inclusion of dairy foods into a moderate calorie restricted diet can increase weight loss and fat loss. Our proposed project extends these prior findings by determining, for the first time, how inclusion of dairy in a calorie-restricted diet changes the amount of visceral adiposity in overweight and obese subjects. The investigators also propose unique studies to evaluate the potential mechanism(s) by which dairy promotes weight and fat loss during dieting, through an examination of adipocyte size, gene expression, and inflammatory markers. The hypotheses under investigation are (1) that inclusion of dairy foods in a modest energy restricted diet will significantly increase body fat loss compared to a control diet; (2) that dairy products in a modest energy restricted diet will result in greater fat loss from intra-abdominal adipose tissue compared to the control, 3) components of dairy products up- or down-regulate the secretion of metabolically-relevant hormones during the postprandial and inter-meal periods, 4) dairy products will promote satiety and/or satiation, 5) dairy foods reduce adipocyte differentiation and/or enhance adipocyte apoptosis, leading to concomitant white adipose tissue (WAT) expression changes for genes playing a role in these processes, 6) dairy foods will reduce adipocyte lipid storage and enhance pathways associated with thermogenesis and mitochondrial function in WAT, as reflected in gene expression changes and reduced adipocyte size, and 7) dairy foods included in a modest energy restricted diet will decrease inflammation in WAT and other tissues, thus decreasing circulating cytokines, increasing zinc status, decreasing expression of inflammatory markers in WAT, and reducing WAT macrophage infiltration.

Detailed Description
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84 overweight and overweight and obese adult males and females will be recruited from the faculty, staff, and student populations at University of California-Davis as well as the greater Davis and Sacramento communities. Each intervention arm will require 42 adults; 35 for statistical power on weight loss + 14 more for attrition during the weight loss intervention. Statistical power for fat loss requires only 20 subjects/treatment arm. Subjects will be enrolled in 7 cohorts of 12 each and will be randomly assigned to either control or dairy diets. Subjects will meet the following additional inclusion and exclusion criteria:

Official Title
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Role of Dairy Foods to Enhance Central Fat and Weight Loss With Moderate Energy Restriction in Overweight and Obesity Individuals

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Other: high dairy diet
* Other: Low Dairy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) 28 -3 4.9 kg/m2 Age 20-45 years for females, age 20-50 for males Low calcium diet (determined by food frequency and diet history): < 1 serving of dairy foods and total dietary Ca intake from all sources not to exceed 600 mg/d . No more than 3 kg weight loss during past three months Negative pregnancy test at entry prior to DXA and abdominal CT scan; pregnancy testing will be repeated done at 6 weeks of diet intervention to insure that women do not become pregnant during the energy restriction period. Should a woman become pregnant she will be dismissed from the protocol. Pregnancy testing will also be done at the end of the study prior to DXA and abdominal CT scans Exclusion Criteria: BMI<28or>37. BMI greater than 37 indicates another level of obesity and the potential for numerous obesity related endocrine changes and substrate utilization abnormalities. Type II diabetes requiring the use of any oral anti-diabetic agent and/or insulin (because of confounding effects on body weight regulation). Fasting glucose > 110 mg/dl. Adverse response to study foods (lactose intolerance, dairy intolerance, dairy allergy; this will be determined by self-report. High calcium diet (determined by food frequency and diet history): Greater than 600 mg calcium per day from all sources (Ca supplements, dairy foods and other dietary sources). History or presence of significant metabolic disease which could impact on the results of the study (i.e. endocrine, hepatic, renal disease). Use of hypertension or lipid altering medications. Resting blood pressure > 160/100 mg/Hg Total cholesterol > 300mg/dl or triglyceride value > 400 mg/dl or LDL > 160 mg/dl. History of eating disorder Presence of active gastrointestinal disorders such as malabsorption syndromes Pregnancy or lactation Use of obesity pharmacotherapeutic agents within the last 12 weeks Use of over-the-counter anti-obesity agents (e.g. those containing phenylpropanolamine, ephedrine and/or caffeine) within the last 12 weeks Use of calcium supplements in the past 12 weeks Recent (past four weeks) initiation of an exercise program Recent (past twelve weeks) initiation of hormonal birth control or change in hormonal birth control regimen Use of tobacco products. Exercise more than 30 minutes/day - greater than this may influence substrate utilization.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Diet with 3-4 servings of dairy-rich foods/day | Other: high dairy diet<br>* 12 week energy restriction with 3-4 servings of dairy foods/day.<br>|
| Placebo Comparator: 2<br>Low Dairy < 1 serving of dairy food/day | Other: Low Dairy<br>* less than 1 serving of dairy foods per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Weight measured in kg | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in body fat | Total body fat assessed using dual energy X-ray absorptiometry (DXA) | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in intra-abdominal adipose tissue (IAAT) | Intra-abdominal adipose tissue IAAT volume measured in cubic centimeters using computed tomography (CT) transabdominal slices | measured at end of run-in diet and after 12 weeks of study diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in subcutaneous adipose cell number and size | Subcutaneous adipose tissue samples obtained by needle biopsy prepared for histological examination of cell number and size in square micrometers (uM2) | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in subcutaneous adipose tissue inflammation | Subcutaneous adipose tissue samples obtained by needle biopsy were prepared for histological examination of the number of macrophages. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in subcutaneous adipose tissue gene expression | Subcutaneous adipose tissue samples obtained by needle biopsy were prepared for RNA extraction | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in insulin | Serum insulin concentration (pmol/L) measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in glucose | Plasma glucose concentration (mmol/L) measured using standard clinical methods | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in total cholesterol | Serum cholesterol concentration (mmol/L) measured using standard clinical methods | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in low density lipoprotein (LDL) cholesterol | Serum LDL cholesterol concentration (mmol/L) measured using standard clinical methods | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in high density lipoprotein (HDL) cholesterol | Serum HDL cholesterol concentration (mmol/L) measured using standard clinical methods | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in vitamin D (calciferol) metabolites | Serum 25-OH Vitamin D (nmol/L) and 1,25 (OH)2 vitamin D concentration (pmol/L) measured using radioimmunoassay (RIA) | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in leptin | Serum leptin concentration (ng/ml) measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in adiponectin | Serum adiponectin concentration (ug/mL) measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in inflammatory cytokines | Serum inflammatory cytokine concentration (pg/mL) measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in high sensitivity C-reactive protein (hs-CRP) | Serum hs-CRP concentration (mg/L) measured using immunoassay | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in amylin | Serum amylin concentration measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in peptide-YY (PYY) | Serum PYY concentration measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in cholecystokinin (CCK) | Serum CCK concentration measured using radioimmunoassay | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in glucagon like peptide-1 (GLP-1) | Serum GLP-1 concentration measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in gastric inhibitory peptide (GIP) | Serum GIP concentration measured using multiplex technology. | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in sun exposure | Sun exposure was estimated from a personal diary kept weekly for recording time outdoors in hourly increments from 7 am to 7 pm combined with a clothing and sunscreen use standard key. Ultraviolet B (UVB) data was collected from various regional climate stations enrolled in the USDA UVB Monitoring Research Program (UVMRP). | measured twice per week for 12 consecutive weeks of study diet | 
| Change in skin reflectance | Spectrophotometric measure of skin pigmentation for assessment of vitamin D status | measured at end of run-in diet and after 12 weeks of study diet | 
| Change in salivary cortisol in response to a meal | Cortisol concentration measure by high sensitivity enzyme linked immunoassay (nmol/L) | 15 minutes before, and 30, 45 and 60 min after lunch | 
| Change in salivary cortisol in response to a buffet | Cortisol concentration measure by high sensitivity enzyme linked immunoassay (nmol/L) | before and 30 min after buffet | 
| Change in salivary cortisol in response to weight loss | Cortisol concentration measure by high sensitivity enzyme linked immunoassay (nmol/L) | measured at end of run-in diet and after 12 weeks of study diet | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dairy foods, weight loss, fat loss, metabolic regulation