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

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.

Study Overview

• Status: Completed
• Conditions: Cholesterol Metabolism; Ketone Metabolism
• Intervention / Treatment: Other: Standard American diet; Other: Very low carbohydrate diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Vallejo, California, United States, 94592
      • Touro University California

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Touro University, California
• Investigators: Principal Investigator: Grace M Jones, PhD, Touro University, California

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2019
• Primary Completion (Actual): April 18, 2019
• Study Completion (Actual): April 18, 2019

Study Registration Dates

• First Submitted: March 29, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: ketogenic diet; carbohydrate; LDL cholesterol
• Other Study ID Numbers: M-0419

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No