Mechanism of Ketogenic Diet-Induced Hypercholesterolemia

March 19, 2026 updated by: Washington University School of Medicine
Very-low carbohydrate ketogenic diets can dramatically increase blood cholesterol levels, particularly in normal-weight people, for reasons that are not well understood. This study will enroll normal-weight adults, will identify "responders" who develop high cholesterol on a ketogenic diet, and will measure rates of production and removal of certain types of cholesterol-carrying particles called lipoproteins in responders. The results will clarify the mechanism by which a ketogenic diet can cause high cholesterol in certain susceptible people.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study will evaluate the mechanism of ketogenic diet-induced hypercholesterolemia in susceptible normal-weight adults. The first stage of screening will identify eligible young adults who are normal-weight and at low cardiovascular risk. The second stage of screening will identify "responders" who demonstrate susceptibility to ketogenic diet-induced hypercholesterolemia by displaying an increase in LDL-cholesterol concentration after a 3-week screening ketogenic diet. Responders will be eligible to complete a randomized crossover clinical study at Washington University School of Medicine in St. Louis, MO. The randomized crossover study will involve isotope tracer studies of lipoprotein and cholesterol kinetics after two separate 4-week dietary interventions [ketogenic diet and control diet], conducted in random order with a 4-week washout period between interventions. All food will be provided to the participants as packed-out meals. Certain outcomes will use data from the screening process, comparing screen successes and screen failures to evaluate factors that could influence susceptibility to ketogenic diet-induced hypercholesterolemia.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Max C Petersen, M.D., Ph.D.
  • Phone Number: 314-362-8352
  • Email: max.p@wustl.edu

Study Locations

  • United States
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
          • Nikki Plassmeyer, M.A., R.D.N., L.D.
          • Phone Number: (314) 362-0590
          • Email: nikkip@wustl.edu
        • Contact:
          • Max C Petersen, M.D., Ph.D.
          • Phone Number: 314-362-8450
          • Email: max.p@wustl.edu
        • Principal Investigator:
          • Max C Petersen, M.D., Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. age ≥ 18 and < 40 years
  2. BMI ≥ 18.5 and < 25.0 kg/m2
  3. baseline serum LDL-c < 150 mg/dL (< 3.9 mmol/L)
  4. baseline serum TG < 100 mg/dL (< 1.1 mmol/L)
  5. HbA1c ≤ 5.6%.

Exclusion Criteria:

  1. personal or family history of familial hypercholesterolemia
  2. current use of lipid-lowering drugs
  3. currently on a ketogenic diet and unwilling to change diet
  4. current tobacco use
  5. hypertension
  6. prediabetes or diabetes
  7. elevated Lp(a) > 6.5% of ApoB-containing lipoproteins at baseline
  8. oral contraceptive use
  9. contraindication to heparin
  10. known atherosclerotic cardiovascular disease
  11. unwilling to abstain from alcohol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A
Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period.
Behavioral: Ketogenic Diet
Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.
Behavioral: Control Diet
Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.
Experimental: B
Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period.
Behavioral: Ketogenic Diet
Participants will consume an isocaloric ketogenic diet for 4 weeks with all food provided as packed-out meals.
Behavioral: Control Diet
Participants will consume an isocaloric control diet for 4 weeks with all food provided as packed-out meals.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
VLDL-ApoB100 production rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
VLDL-ApoB100 fractional catabolic rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 production rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
IDL-ApoB100 fractional catabolic rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and IDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 production rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
LDL-ApoB100 fractional catabolic rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and LDL-ApoB100 leucine isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride production rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
VLDL-triglyceride fractional catabolic rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL glycerol isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein lipase activity
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by assaying lipoprotein lipase activity in post-heparin plasma
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Plasma lipoprotein profile
Time Frame: At baseline, immediately after the screening ketogenic diet, immediately after the 4-week ketogenic diet intervention period, and immediately after the 4-week control diet intervention period.
Determined by standard clinical chemistry methods and by advanced lipoprotein profiling
At baseline, immediately after the screening ketogenic diet, immediately after the 4-week ketogenic diet intervention period, and immediately after the 4-week control diet intervention period.
Whole-body lipolytic rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma palmitate isotopic enrichment
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Relative contribution of systemic fatty acids to VLDL-triglyceride
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using plasma and VLDL-triglyceride palmitate isotopic enrichment and compartmental modeling
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Cholesterol synthetic rate
Time Frame: Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Determined by using mass isotopomer distribution analysis of deuterium enrichment in plasma cholesterol after labeling the total body water pool with deuterium oxide
Immediately after the 4-week ketogenic diet intervention period and immediately after the 4-week control diet intervention period.
Fat mass
Time Frame: Immediately after the screening ketogenic diet
Determined by using dual-energy X-ray absorptiometry
Immediately after the screening ketogenic diet
Fat-free mass
Time Frame: Immediately after the screening ketogenic diet
Determined by using dual-energy X-ray absorptiometry
Immediately after the screening ketogenic diet
Insulin sensitivity
Time Frame: Immediately after the screening ketogenic diet
Determined by measuring fasting plasma glucose, insulin, and C-peptide
Immediately after the screening ketogenic diet
Thyroid function
Time Frame: Immediately after the screening ketogenic diet
Determined by measuring TSH, free T4, and free T3
Immediately after the screening ketogenic diet
Adipokines
Time Frame: Immediately after the screening ketogenic diet
Determined by measuring plasma leptin and adiponectin
Immediately after the screening ketogenic diet
Cholesterol absorption markers
Time Frame: Immediately after the screening ketogenic diet
Determined by measuring serum campesterol, sitosterol, and cholestanol
Immediately after the screening ketogenic diet

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Max C Petersen, M.D., Ph.D., Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 24, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202409091

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All raw data used to generate descriptive statistics presented in manuscripts incorporating results generated from this study will be included as supplemental data files as and when required. Fully de-identified raw data, including all outcome measures and tracer enrichments from kinetic studies will be available in .csv format, which can be manipulated by many free and commercial software packages. Individual-level data will be shared as allowed by informed consent agreements approved by the Institutional Review Board (IRB).

IPD Sharing Time Frame

Data will be made available upon peer-reviewed publication of the study results or earlier as required by the study sponsor and/or funding sources.

IPD Sharing Access Criteria

FAIR Data Sharing protocols will be applied so that the data will be Findable, Accessible, Interoperable, and Re-usable.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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