Mechanism of Ketogenic Diet-Induced Hypercholesterolemia

Last updated: March 18, 2025
Sponsor: Washington University School of Medicine
Overall Status: Active - Recruiting

Phase

N/A

Condition

Hypercholesterolemia

Treatment

Control Diet

Ketogenic Diet

Clinical Study ID

NCT06894004
202409091
  • Ages 18-39
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

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.

Eligibility Criteria

Inclusion

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

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 Design

Total Participants: 100
Treatment Group(s): 2
Primary Treatment: Control Diet
Phase:
Study Start date:
February 24, 2025
Estimated Completion Date:
November 30, 2030

Study 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.

Connect with a study center

  • Washington University School of Medicine

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

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