Dietary Treatment Study of Fat Synthesis and Risk of Cardiovascular Disease

Study Overview
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Brief Summary
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The purpose of this study is to find out how the amount of fat or sugar in a person's diet, or the number of meals eaten each day, affect the amount of fat that people's bodies make, the types of fats in the bloodstream, and how much fat is stored in the liver. The study is funded by the National Institutes of Health.

Detailed Description
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The study consists of two 10-day feeding periods that are separated by approximately two weeks. During each feeding period all food and beverages to be consumed will be provided by the study. In Study 1, participants will be randomly assigned to receive one of two diets. Both diets are designed to maintain weight at a constant level. The diets are balanced nutritionally and have the same amount of protein. One diet has higher amounts of sugar, while the other has higher amounts of fat. For one 10-day period, the diet will be fed as two large meals ('meal-feeding'). For the other 10-day period, the identical diet will be fed as 8 small meals ('nibbling'). Half of the participants will meal-feed first, while the other half will 'nibble' first. The order of nibbling or meal feeding will be determined randomly. In Study 2, the number of meals eaten per day will remain fixed at three (no nibbling or meal feeding). Participants will receive both the diet higher in sugar and the diet higher in fat. However, they will be randomly assigned to start one followed by the other for each 10-day feeding period. At the end of each 10-day feeding period, participants will spend two nights in a research ward (Clinical Research Center) to undergo testing.

Official Title
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Lipogenesis, Lipoprotein Flux, and CVD Risk: Role of Meal Composition and Frequency

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Other: High sugar/meal feed
* Other: High sugar/nibble
* Other: High fat/meal feed
* Other: High fat/nibble
* Other: High sugar/ 3 meals a day
* Other: High fat/ 3 meals a day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: overweight or obese men and women ages 20-65 years Exclusion Criteria: pregnancy or lactation within the past six months type 1 or 2 diabetes mellitus] AST and ALT above upper limit of normal (ULN) fasting triglyceride or total cholesterol levels >ULN Hgb below the lower of limit of normal positive HIV antibody test or hepatitis serologies use of any antidiabetic medications or lipid-lowering drugs history of surgery for obesity change in body weight >5% within preceding 6 months (self report) claustrophobia, presence of metal implants weight over 350 lbs

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High sugar/meal feed<br>Diet high in simple sugar fed as two large meals daily | Other: High sugar/meal feed<br>* Weight-maintaining diet relatively high in sugar fed as two large meals daily<br>Other: High sugar/nibble<br>* Weight-maintaining diet relatively high in sugar fed as 8 meals daily<br>|
| Experimental: High sugar/nibble<br>Diet high in simple sugar fed as 8 small meals daily | Other: High sugar/meal feed<br>* Weight-maintaining diet relatively high in sugar fed as two large meals daily<br>Other: High sugar/nibble<br>* Weight-maintaining diet relatively high in sugar fed as 8 meals daily<br>|
| Experimental: High fat/meal feed<br>Diet high in fat fed as two large meals daily | Other: High fat/meal feed<br>* Weight-maintaining diet relatively high in fat fed as two large meals daily<br>Other: High fat/nibble<br>* Weight-maintaining diet relatively high in fat fed as 8 small meals daily<br>|
| Experimental: High fat/nibble<br>Diet high in fat fed as 8 small meals daily | Other: High fat/nibble<br>* Weight-maintaining diet relatively high in fat fed as 8 small meals daily<br>|
| Experimental: High sugar/3 meals a day<br>Diet high in simple sugar fed as 3 meals a day | Other: High sugar/ 3 meals a day<br>* Weight-maintaining diet relatively high in sugar fed as 3 meals daily<br>Other: High fat/ 3 meals a day<br>* Weight-maintaining diet relatively high in fat fed as 3 meals daily<br>|
| Experimental: High fat/ 3 meals a day<br>Diet high in fat fed as 3 meals a day | Other: High sugar/ 3 meals a day<br>* Weight-maintaining diet relatively high in sugar fed as 3 meals daily<br>Other: High fat/ 3 meals a day<br>* Weight-maintaining diet relatively high in fat fed as 3 meals daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of meal composition on fractional de novo lipogenesis (fatty acid synthesis) | Differences between high carbohydrate and high fat diets on postprandial de novo lipogenesis De novo lipogenesis will be measured using stable (not radioactive) isotopes given intravenously and orally during feeding. | After 10-day dietary period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of meal frequency on fractional de novo lipogenesis (fatty acid synthesis) | Differences between consuming the same diet as eight small meals per day or two larger meals per day on postprandial de novo lipogenesis. Please see description of measurement of de novo lipogenesis under aim 1. | After 10-day dietary period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diet, Sugar, Cardiovascular, Lipid