Investigating the Production of Lipoproteins and Acetyl-CoA During a Ketogenic Diet

Study Overview
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Brief Summary
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The purpose of this study is to understand how the reduction in dietary carbohydrates in a very-low carbohydrate ketogenic diet impacts the synthesis of cholesterol, fatty acid, and ketones, and the turnover rate of VLDL and chylomicron particles.

Detailed Description
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Participants will consume a standard American diet for one week followed by a very-low carbohydrate ketogenic diet (VLCKD, <50 grams carbohydrate/day) for two weeks. Participants will undergo an oral stable isotope tracer study during each diet to measure de novo synthesis of fatty acid, cholesterol, ketone bodies, and for measurement of apolipoprotein B and triglyceride kinetics.

Official Title
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Investigating the Production of Lipoproteins and Acetyl-CoA During a Ketogenic Diet

Conditions
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Cholesterol Metabolism, Ketone Metabolism

Intervention / Treatment
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* Other: Standard American diet
* Other: Very low carbohydrate diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 18-50 years old Exclusion Criteria: Use of nicotine products Has dietary restrictions Lactose intolerance History of GI disorders, diabetes, liver, kidney, or thyroid disorders Taking hypolipidemic, anti-diabetic, anti-hypertensive, or anti-depression medication Screening plasma triglyceride < 50mg/dl or >500mg/dl Screening glucose > 125mg/dl Screening total and LDL-Cholesterol over 95th %tile for age and sex BP > 160/95 mmHg Weight loss/gain > 5% in the previous 3 months (self-reported)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Baseline diet<br>1 week baseline diet | Other: Standard American diet<br>* Standard American diet with 50% energy from carbohydrate, 30% from fat, and 20% from protein.<br>|
| Experimental: Very low carbohydrate diet<br>2 week very low carbohydrate ketogenic diet | Other: Very low carbohydrate diet<br>* Ketogenic diet with <50g carbohydrate, 60-75% energy from fat, and 20% from protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total cholesterol | Change in serum total cholesterol between Day 3-7 (average value) to Day 17-21 (average value) | Day 3-7 to Day 17-21 | 
| Change in low density lipoprotein (LDL) cholesterol | Change in serum LDL cholesterol between Day 3-7 (average value) to Day 17-21 (average value) | Day 3-7 to Day 17-21 | 
| Change in high density lipoprotein (HDL) cholesterol | Change in serum HDL cholesterol between Day 3-7 (average value) to Day 17-21 (average value) | Day 3-7 to Day 17-21 | 
| Change in apolipoprotein B (apoB) kinetics | Change in apoB turnover rates in LDL and very low density lipoprotein plasma fractions as measured using 2H2 leucine incorporation into apoB and mathematical modeling | Day 3-7 to Day 17-21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fractional hepatic de novo lipogenesis | Measured by the detection of incorporated 1-13C sodium acetate into palmitate in triglyceride rich lipoproteins (TRL) | Day 3 to Day 17 | 
| Change in fractional cholesterol synthesis | Measured by the detection of incorporated 1-13C sodium acetate into cholesterol in plasma | Day 3 to Day 17 | 
| Change in ketone body synthesis | Measured by the detection of incorporated 1-13C sodium acetate into ketone bodies in plasma | Day 3 to Day 17 | 
| Change in TRL-triglyceride kinetics | Change in TRL- triglyceride assembly rates as measured using 2-13C glycerol and mathematical modeling | Day 3 to Day 17 | 
| Change in triglyceride lipolysis | Measured by the dilution of administered 2-13C glycerol in plasma | Day 3 to Day 17 | 
| Change in serum glucose concentration | Change in fasting and postprandial serum glucose levels | Day 3 to Day 17 | 
| Change in serum free fatty acid concentration | Change in fasting and postprandial serum free fatty acid levels | Day 3 to Day 17 | 
| Change in serum insulin concentration | Change in fasting and postprandial serum insulin levels | Day 3 to Day 17 | 
| Change in serum ketone body concentration | Change in fasting and postprandial ketone body levels | Day 3 to Day 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, LDL cholesterol, carbohydrate