Ketogenic Diet for High Cholesterol

Recruiting at 1 trial location

Overseen By Nikki Plassmeyer, M.A., R.D.N., L.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Lipid-lowering drugs, Oral contraceptives

Disqualifiers: Hypertension, Diabetes, Tobacco use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates why some normal-weight individuals experience high cholesterol on a ketogenic diet, which is very low in carbohydrates. Researchers will examine how the body processes and removes cholesterol-carrying particles, known as lipoproteins, in those who develop high cholesterol on this diet. Participants will follow either a ketogenic diet or a control diet, with a break in between. The trial seeks adults who are not currently on a ketogenic diet and do not have conditions like high blood pressure, diabetes, or a family history of high cholesterol. As an unphased trial, this study offers a unique opportunity to contribute to understanding dietary impacts on cholesterol.

Will I have to stop taking my current medications?

If you are currently using lipid-lowering drugs, you cannot participate in this trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

What prior data suggests that the ketogenic diet is safe for normal-weight adults?

Research has shown that a ketogenic diet can significantly increase LDL cholesterol levels. In some studies, participants experienced an increase in LDL cholesterol by as much as 245%. LDL cholesterol is often called "bad" cholesterol because high levels can raise the risk of heart disease.

However, these cholesterol levels typically return to normal after stopping the diet. Other studies have found that the ketogenic diet can also raise HDL cholesterol, known as "good" cholesterol, and help lower blood sugar levels.

Overall, while the ketogenic diet can change cholesterol levels, its effects on heart health remain mixed. More research is needed to fully understand these effects. It is advisable to consult a doctor before making major dietary changes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for high cholesterol involve medications like statins, which work by blocking a substance your body needs to make cholesterol. However, the ketogenic diet offers a unique approach by altering your body's metabolism. This diet is high in fats and low in carbohydrates, prompting the body to burn fats instead of carbs for energy, which can potentially lower cholesterol levels naturally. Researchers are excited about this alternative because it could provide a non-pharmaceutical option for managing cholesterol, possibly reducing medication reliance and associated side effects.

What evidence suggests that the ketogenic diet could affect cholesterol levels?

Research has shown that the ketogenic diet can affect cholesterol levels in various ways. Some studies find that this diet can lower overall cholesterol and triglycerides (a type of fat in the blood), but it might not significantly change HDL ("good" cholesterol) and LDL ("bad" cholesterol) levels. Other research suggests that the ketogenic diet could raise total cholesterol and LDL cholesterol, which might pose a concern for heart health. However, reports also indicate that it can boost HDL cholesterol levels, which is beneficial. The mixed effects of the diet on cholesterol highlight the need for more research to better understand its impact, especially for individuals who experience an increase in cholesterol levels. In this trial, participants in Arm A will follow the Ketogenic Diet first, while those in Arm B will start with the Control Diet, allowing for a direct comparison of the diet's effects on cholesterol. ^{1 6 7 8 9}

Who Is on the Research Team?

Max C Petersen, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for normal-weight adults who experience a significant increase in cholesterol levels when following a very-low carbohydrate ketogenic diet. The study aims to identify 'responders'—individuals whose cholesterol levels rise—and analyze their lipoprotein metabolism.

Inclusion Criteria

BMI must be between 18.5 and 25.0 kg/m2

Baseline serum LDL-c must be less than 150 mg/dL (less than 3.9 mmol/L)

Baseline serum TG must be less than 100 mg/dL (less than 1.1 mmol/L)

Exclusion Criteria

I have prediabetes or diabetes.

I have been diagnosed with heart disease related to artery blockage.

Current tobacco use

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

Dietary Intervention

Participants undergo two separate 4-week dietary interventions (ketogenic diet and control diet) in a randomized crossover design with a 4-week washout period between interventions

12 weeks

Multiple visits (in-person) for meal provision and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet

Trial Overview The study compares the effects of a ketogenic diet versus a control diet on blood cholesterol levels. It focuses on how these diets influence the production and removal of lipoproteins, which carry cholesterol through the bloodstream.

How Is the Trial Designed?

Group I: B Experimental Treatment 2 Interventions

Arm B will complete the Control Diet intervention first, followed by the Ketogenic Diet intervention after a 4-week washout period.

Group II: A Experimental Treatment 2 Interventions

Arm A will complete the Ketogenic Diet intervention first, followed by the Control Diet intervention after a 4-week washout period.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

The ketogenic diet (KD) can lead to significant increases in total cholesterol and low-density lipoprotein (LDL) cholesterol, especially in lean individuals, highlighting the need for careful lipid monitoring during the diet.

Improvements in cholesterol levels were observed after discontinuing the KD, suggesting that while the diet may aid in weight loss and glycemic control, it can have adverse effects on lipid profiles that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profound Elevation in LDL Cholesterol Level Following a Ketogenic Diet: A Case Series. Crosier, R., McPherson, R.[2022]

The ketogenic diet (KD) is effective in controlling drug-refractory seizures in children and adolescents, but it is associated with recurrent dyslipidemia, particularly hypercholesterolemia, which can negatively impact lipid profiles.

While KD has clear benefits for seizure control, it may increase cardiometabolic risk due to structural changes in low-density lipoprotein (LDL) particles, suggesting a need for further investigation into lipid and oxidative metabolism in patients on this diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet in epileptic children: impact on lipoproteins and oxidative stress. Lima, PA., de Brito Sampaio, LP., Damasceno, NR.[2017]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0146280624000410

Invited Review Article Ketogenic diet and cardiovascular risk the ketogenic diet led to a significant decrease in total cholesterol and triglycerides levels without significant changes in HDL and LDL levels.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10210275/

Effects of ketogenic diet on health outcomes On the one hand, VLCKD is very effective in producing weight loss while preserving muscle mass in adults with overweight or obesity, with ...

3. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101686

Longitudinal Data From the KETO-CTA Study: Plaque ... A total of 100 individuals exhibiting KD-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglycerides ≤80 mg/dL ...

4. pennmedicine.org pennmedicine.org/news/a-cardiologists-take-on-the-keto-diet

A cardiologist's take on the keto diet That's supported by several studies, like a 2017 review in the journal Nutrients that found that the keto diet improved HDL “good” cholesterol ...

5. ajcn.nutrition.org ajcn.nutrition.org/article/S0002-9165(24)00445-3/fulltext

Impact of the ketogenic diet as a dietary approach on ... The ketogenic diet group showed an increase in TC (MD: 0.36 mmol/L; 95% CI: 0.15, 0.57; I2: 85.1%) (Figure 2B), LDL cholesterol (MD: 0.35 mmol/L ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10121782/

Dramatic elevation of LDL cholesterol from ketogenic-dieting When patients abstained from the ketogenic diet, their LDL cholesterol levels decreased by an average of 174 mg/dL representing a 220% decrease ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666667723000892

129 the impact of the ketogenic diet on cholesterol levels in ... After strict adherence to the ketogenic diet for a mean timeframe of 12.3 months, the mean LDL level increased by 245%. Patients who discontinued the ketogenic ...

8. jacc.org jacc.org/doi/10.1016/j.jacadv.2024.101109

Carbohydrate Restriction-Induced Elevations in LDL- ... A ketogenic low-carbohydrate high-fat diet increases LDL cholesterol in healthy, Young, normal-weight Women: a randomized controlled Feeding ...

9. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02874-y

Effects of ketogenic diet on health outcomes: an umbrella ... However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate ...