Controlled Clinical Study to Determine Novel Health Benefits of Cheese Consumption

Study Overview
=================
Brief Summary
-----------------
To determine the effects of high cheese diets varying in carbohydrate content on markers of disease risk.

Detailed Description
-----------------
Summary of Proposed Research: This project will involve four controlled 4 wk feeding periods in individuals with metabolic syndrome (currently 1/3 of US adults). After a 2 wk run-in period, 20 subjects will be fed one of three diets in a randomized and balanced order: a typical American High-Carb diet high in cheese (6 oz/day), a High-Carb diet low in cheese (0 oz/day), or a Moderate-Carb, high-cheese diet (6 oz/day), Low-Carb, high cheese where cheese displaces an isocaloric amount of carbohydrate. There will be a 2 wk washout period separating trials during which subjects consume their normal diet. Specific menus will be designed for each feeding phase and all food will be prepared for subjects. Testing will occur at baseline and after each feeding period. Measures of cholesterol beyond standard LDL- and HDL-cholesterol will be done by examining lipoprotein particle size, apolipoproteins, and fatty acid composition [i.e., accumulation of saturated fat in blood and tissues, palmitoleic acid (highly linked to cardiovascular disease), and detection of phytanic acid (a uniquely bioactive fatty acid in dairy fat)]. Changes in whole body and regional fat, including measures of visceral fat and liver fat, will be examined non-invasively by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI).

Official Title
-----------------
Controlled Feeding Study to Show Effects of Manipulating Carbohydrate and Cheese on Health Markers In Individuals With Metabolic Syndrome

Conditions
-----------------
Metabolic Syndrome X

Intervention / Treatment
-----------------
* Other: Nutritional and Dietary Manipulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Waist circumference (≥101.6 cm men, ≥88.9 cm women) Blood pressure (≥130/85 mm Hg) or current use of antihypertensive medication Fasting plasma glucose (≥100 mg/dL) Triglycerides (≥150 mg/dL) HDL-C (<40 mg/dL men, <50 mg/dL women) Exclusion Criteria: Hypercholesterolemia Diabetes Liver, kidney or other metabolic or endocrine dysfunction, gastrointestinal disorders Regular smokers Lactose-intolerant Consume excessive amounts of alcohol (>3 drinks/d) Have used cholesterol, diabetic, antibiotic or antifungal medications in the past 3 months Women who are pregnant or lactating Participants taking any probiotics or supplements known to affect serum lipid levels, inflammation, antioxidant status or the gut microbiota will be asked to discontinue use to allow for washout of any metabolic effects.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Carbohydrate No Cheese<br>Intervention: Nutritional and Dietary Manipulation. This arm will be provided food with an approximate macronutrient breakdown of: 55% CHO, 20% PRO and 25% fat with  6oz Cheese (gouda or cheddar) per day being used as a fat source. | Other: Nutritional and Dietary Manipulation<br>* Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff. Participants will be asked to exclusively eat what is provided to them in efforts to control any dietary effects.<br>|
| Experimental: High Carbohydrate High Cheese<br>Intervention: Nutritional and Dietary Manipulation. This arm will be provided food with an approximate macronutrient breakdown of: 55% CHO, 20% PRO 25% and Fat 25% with  6oz Cheese (gouda or cheddar) per day being used as a fat source. | Other: Nutritional and Dietary Manipulation<br>* Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff. Participants will be asked to exclusively eat what is provided to them in efforts to control any dietary effects.<br>|
| Experimental: Mod. Carbohydrate High Cheese<br>Intervention: Nutritional and Dietary Manipulation. This arm will be provided food with an approximate macronutrient breakdown of: 30% CHO, 20% PRO and 50% Fat with  6oz Cheese (gouda or cheddar) per day being used as a fat source. | Other: Nutritional and Dietary Manipulation<br>* Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff. Participants will be asked to exclusively eat what is provided to them in efforts to control any dietary effects.<br>|
| Experimental: Low Carbohydrate High Cheese<br>Intervention: Nutritional and Dietary Manipulation. This arm will be provided food with an approximate macronutrient breakdown of: 10% CHO, 20% PRO and 70% Fat with  6oz Cheese (gouda or cheddar) per day being used as a fat source. | Other: Nutritional and Dietary Manipulation<br>* Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff. Participants will be asked to exclusively eat what is provided to them in efforts to control any dietary effects.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Fatty Acid Composition and Lipoprotein Analysis | Blood analysis for Fatty Acid Composition and Lipoproteins will by conducted by Lipid Technologies and Quest Diagnostics, respectively. | Through study completion, an average of 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Composition as Assessed by DEXA and MRI | Participants will undergo both DEXA and MRI scans, conducted by trained professionals. DEXA will be used to determined subcutaneous adiposity. MRI post-imaging analyses will determine both hepatic and visceral fat content. | Through study completion, an average of 2 years. | 
| Change in Blood-based Inflammation Markers | Inflammatory biomarkers in the blood will be assessed using a Multiplex ELISA system. The inflammatory markers to be measured are: IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13 and TNF-α. | Through study completion, an average of 2 years. | 
| Change in Blood Metabolite Profiles | NMR spectroscopy (600 Mhz) will be used to obtain metabolic profiles of serum samples. | Through study completion, an average of 2 years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diet Intervention, Metabolic Syndrome, Feeding Study, Prediabetes